Vascular News 81 – January 2019

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Meta-analysis finds a higher risk of death in the long term when paclitaxel-coated devices are used in the leg

New data published in the Journal of the American Heart Association (JAHA), suggest that there is an increased risk of death at two and five years following the use of paclitaxelcoated balloons and stents in the femoropopliteal artery. While the authors, Konstantinos Katsanos (Patras, Greece) and colleagues, write in JAHA that this meta-analysis provides good statistical evidence to back these findings, some leading physicians state that it lacks individual patient-level data from the randomised controlled trials.

I

n the JAHA paper, the investigators write that several randomised controlled trials have already shown that paclitaxel-coated balloons and stents significantly reduce the rates of vessel restenosis and target lesion revascularisation after lower extremity interventions.

The investigators conducted a systematic review and meta-analysis of randomised controlled trials investigating paclitaxel-coated balloon angioplasty or paclitaxel-coated metal stents in the femoral and/or popliteal arteries. In all, 28 randomised controlled trials with 4,663 patients (89% intermittent claudication) were analysed. As reported in JAHA, they last screened medical databases, online content and regulatory authority filings in August 2018.

The primary safety measure was all-cause patient death, analysed at different time points. “Risk ratios and risk differences were pooled with a random effects model,” the authors write.

At one year, all-cause patient death (28 randomised controlled trials with 4,432 patients) was similar between 17 paclitaxel-coated devices and control arms (2.3% vs. 2.3% crude risk of death). All-cause death at two years (12 randomised controlled trials with 2,316 patients) was significantly increased in the case of paclitaxel vs. control (7.2% [101 deaths in 1,397 patients] vs. 3.8% [35 deaths in 919 patients] crude risk of death, number-needed-to-harm [NNH]: 29 patients [95% CI: 19–59]). Long-term risk of all-cause death up to five years (three randomised controlled trials with 863 patients) increased further in case of paclitaxel (14.7% [78 deaths out in 529 patients] vs. 8.1% [27 deaths in 334 patients] crude risk of death, NNH: 14 patients [95% CI: 9–32]).

Katsanos and colleagues further write that metaregression showed a significant relationship between exposure to paclitaxel (dose-time product) and absolute

Konstantinos Katsanos

risk of death (0.4±0.1% excess risk of death per paclitaxel mg-year; p<0.001). “Trial sequential analysis excluded false-positive findings with 99% certainty (2-sided alpha, 1.0%),” they say.

These data led the authors to conclude that there is increased risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery. “Further investigations are urgently warranted,” they write.

Katsanos told Vascular News about the key data from the JAHA paper. “My colleagues and I have performed a meta-analysis of 28 studies comprising more than 4,600 patients (nearly 90% of these were claudicants) who were randomly allocated to either receive a paclitaxel-coated device (balloon or stent) in the femoropopliteal segment or a control non-drugcoated treatment. Our meta-analysis was restricted to well-designed randomised controlled trials alone to avoid comparing ‘apples’ with ‘oranges’. Statistical inference has identified an alarmingly higher rate of death after the first year in the case of the paclitaxelContinued on page 6

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Alberto Muñoz:

Profile

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Draft NICE aortic guidelines cause endovascular controversy

For the vascular community in the UK, discourse on guidelines in 2018 increasingly came to focus on the proposed guidelines document from the National Institute for Health and Care Excellence (NICE), which in a draft published in May outlined the contentious recommendation for open repair of aortic aneurysms, rather than endovascular aneurysm repair (EVAR).

The final guidelines, which were initially scheduled for publication in November 2018, remain unpublished at the time of writing, with the publication date “to be concluded” according to an online statement by NICE. THE DOCUMENT STATES that patients with unruptured infrarenal abdominal aortic aneurysms should not be offered EVAR if open surgical repair is suitable—nor should EVAR or complex EVAR be offered if open repair is unsuitable due to the patient’s anaesthetic and medical condition. The guidelines committee bases its recommendations largely on the EVAR 1 and EVAR 2 trials, which on 15-year follow-up found a lower mortality for open repair than for EVAR at 15 years.

Roger Greenhalgh of Imperial College in London, UK, was the principal investigator of the EVAR 1 and Continued on page 4

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Aortic aneurysm repair

Draft NICE aortic guidelines cause endovascular controversy Continued from page 1

EVAR 2 trials. Speaking at the Vascular Societies’ Annual Scientific Meeting (VSASM; 27–29 November, Glasgow, UK), Greenhalgh made a case against the draft guidelines, arguing the data from the trials had been misinterpreted and that their application lacked appropriate context. He outlined limitations to the use of mortality outcomes, and presented new data to illustrate reasons for these mortality rates, which could be caused by suboptimal follow-up protocols following the procedure, Greenhalgh argued.

Greenhalgh’s talk, titled “Optimising post-operative surveillance and intervention following endovascular repair of abdominal aortic aneurysms”, was a paper put forward to NICE by Greenhalgh and colleagues in the EVAR trials post-operative surveillance group—an international multi-disciplinary collaboration between triallists, health economists and statisticians—and published in the British Journal of Surgery in 2018.

“Most of you are aware of the EVAR trials, and the problem that presented itself in the 15-year results,” Greenhalgh said at VSASM, referring to the fact that at 15 years, the EVAR trial data showed higher rates of aneurysm-related and total mortality during the last eight years of follow-up for patients who had EVAR than those who had open repair. “It was found that the aneurysm-related mortality was mainly caused by secondary rupture, and the all-cause mortality significant difference—to everyone’s surprise—was largely due to aneurysm-related mortality and some cancer deaths.”

Having established that the separation of mortality rates for open repair and EVAR in the EVAR trials were caused by aneurysm-related deaths due to secondary rupture in the EVAR arm, Greenhalgh moved to investigate how this problem might be mitigated. Referring to a “brilliant analysis” showing the trajectories of sac diameters over time by type of event in the EVAR trials, Greenhalgh explained: “If you measure the diameter of the sac around the endovascular device over time, you will see … if you perform a rupture-preventing intervention, you convert the shape of this trajectory towards a safer outcome which does not lead to rupture.” Corroborating this data with follow-up statistics provided by Maarit Venarmo and her vascular team in Helsinki, Finland, which showed similar trajectories on analysis.

Greenhalgh further elaborated that rupture following early EVAR procedures may have been more prevalent, as reintervention techniques and technology continue to improve over time. However, rupture-preventing interventions are also largely dependant on maintained monitoring of aneurysm sac growth—an area upon which Greenhalgh could further shed some light. Regarding the

Editor-in-chief:

If the EVAR trials were repeated today

Also speaking at the VSASM, Andrew Bradbury, who chaired the scientific guidelines committee for NICE, explained the process of the highly structured and methodical process of the institute’s guidelines production. Bradbury emphasised the reasoning behind the draft guidelines, including the prioritisation of randomised controlled trial data and the use of health economics in the UK National Health Service (NHS). At the same time, Bradbury acknowledged that a considerable amount of input from the vascular community had been considered in the months following the draft publication, and suggested there may be some changes to the final version.

Ultimately however, Bradbury maintained at that the EVAR trials, “if they were repeated today, they would likely show more or less the same outcomes,” and added that such a trial might be ethically questionable, considering the mortality outcomes of EVAR 1. The NICE draft guidelines nevertheless state that complex EVAR should not be offered to patients with an unruptured AAA if open repair is a suitable option,

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Roger Greenhalgh

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EVAR trials, he reported: “The issue was that in the first six months there was reasonable follow-up, but after a year follow-up began to drop consistently year by year, and by the nine-year follow-up only 10% of the patients were being followed.”

This is a finding that again was corroborated by the Helsinki cohort, leading the the group to establish this was not merely a “UK-only problem”—as Venarmo observed the 90% follow-up rate in the first six months dropping to 40% at five years. Greenhalgh commented that “while that is not perfect, it is better than the UK”, but maintained that follow-up rate drop-off over time remains “a widespread problem”. The clinical significance of this issue, Greenhalgh said, is that “current EVAR follow-up protocols are indeed suboptimal, and the EVAR procedure requires lifelong annual surveillance.”

“From repeated annual sac diameter measurements,” Greenhalgh continued, “we can predict that 40% of patients are classified as low risk, and no hospital follow-up is required. However, 85% of patients need rupture-preventing reintervention within two years.”

Having established the threshold for criteria of vascular centre referral, Greenhalgh pointed out that the improved structure for referral and follow-up protocol, which was not yet applied at the time of the EVAR trials, directly impact the aneurysm-related mortality rate while also improving cost-efficiency post-EVAR.

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Roger Greenhalgh

“except as part of a randomised controlled trial comparing complex EVAR with open surgical repair.”

To this point, Greenhalgh presented data from a discrete event simulation—a predictive model based on the real data from patients in the EVAR trials, “constructed to estimate the incidence of complications, ruptures and deaths that would have occurred under alternative surveillance protocols”. The data, which is currently under review for publication, highlights the cost per quality-adjusted life year which shows favourable outcomes for EVAR when implementing an updated follow-up protocol post-EVAR, compared to the recommendations favouring open repair as outlined in the NICE draft guidelines.

The use of this simulation, Greenhalgh explained, serves to update the trial data according to current contexts and provides valuable insight quickly, as “patients need benefit now—not after another 15 years at high costs of a repeat trial.”

The reason for delay in publication of the final guidelines has not been disclosed, but may have been caused by new evidence submitted prior to publication including the analysis presented by Greenhalgh, along with the public outcry at the draft which was a central talking point not only at the VSASM but also at several international meetings including VETHsymposium (13–17 November, New York, USA), as the NICE scientific guidelines committee currently continues to review the considerable input given by the vascular and endovascular community.

Please contact the Vascular News team with news or advertising queries Tel: +44 (0) 20 7736 8788 Published by: BIBA Medical, 526 Fulham Road London, UK SW6 5NR Tel: +44 (0) 20 7736 8788

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6

Jan

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19 81

Paclitaxel-eluting devices

Meta-analysis finds a higher risk of death in the long term when paclitaxel-coated devices are used in the leg Continued from page 1

coated device group; risk ratio 1.68 at two years and risk ratio 1.93 at four to five years of follow-up. Our findings were robust on multi-level sensitivity and subgroup analyses and we calculated that one out of 14 patients is expected to die because of paclitaxel up to five years (NNH=14).

“Overall, we would welcome collection and reporting of longer-term follow-up in case of all commercial clinical studies to help confirm, or refute our findings.

It is also imperative to perform individual patient data time-to-event analysis for each individual device beyond the first year in combination with an in-depth query of potential confounders and predictors. To paraphrase one of Sherlock Holmes’ quotes: ‘When you have eliminated the impossible, whatever remains, however improbable, must be the truth’,” he said.

Vascular News collected early reaction on the dataset from key opinion leaders in the field.

Can the mortality risk be broken down by device type and make?

“The authors seem to have conducted a well-designed meta-analysis and subsequent statistical analysis of the incidence of mortality after the use of paclitaxelcoated stents and balloons in the lower extremity arteries. The authors’ findings are surprising, but on the evidence presented suggest that there may be an increased risk of death in the long term after patients have been treated with drug-coated devices. It would be interesting to know whether the authors found a significant difference in mortality between drugcoated balloons and stents. Also, did the authors find a relationship between mortality and the different types of devices? For example, how did the mortality risk play out with the Lutonix drug-coated balloon (DCB; BD) versus. IN.PACT DCB (Medtronic)?” questioned Robert Morgan (St George’s University Hospitals NHS Foundation Trust, London, UK, and president of the Cardiovascular and Interventional Radiological Society of Europe [CIRSE]).

“It is an obvious flaw of the data that causes of death were not uniformly recorded in the studies analysed.

Despite the authors’ rigorous statistical evaluation, there must still be a risk that the apparent increased mortality with these devices is due to other factors unrelated to paclitaxel. Clearly, the authors’ findings suggest that more investigation is warranted into the potential mortal effects of paclitaxel-coated devices in the peripheral arteries. It is a matter of discussion whether all ongoing and future trials involving drug-eluting devices may require long-term, and even life-long follow-up to look at the potential effects on mortality of these devices. It is a matter for conjecture whether if this were to be the case, the effect on industry’s enthusiasm to fund such trials might be tempered,” Morgan added.

Does this statistical mining of data bring to mind the fate of the COX-2 inhibitors?

Ziv Haskal (University of Virginia School of Medicine, Charlottesville, USA and editor-in-chief of the Journal of Vascular and Interventional Radiology [JVIR]) emphasised the importance of numbers. “Sometimes certain truths may only be suggested with the power of numbers. Katsanos et al have pooled and mined prospective comparative data on nearly 4,500 patients who underwent lower extremity revascularisation with and without local paclitaxel by balloon or stent. The stunning new observation of this sophisticated analysis is a nearly doubled rate of increased death at two and five years after intervention. This alarming finding brings to mind the similar means by which COX-2 inhibitors were first linked to increased cardiovascular mortality— notably, statistical findings were dismissed early on when

they suggested a painful truth about these high value (and high margin) drugs. Now those medications have been withdrawn, or are used with very stringent consideration.

As healthcare providers and scientists, we cannot fall prey to the urge to simply dismiss Katsanos et al’s findings and then focus on the next-presented, exciting, drug-coated device trial abstract. Long-term follow-up data must be mandated in all paclitaxel device trials, mechanistic studies must be undertaken, and replicative analyses considered. In the meanwhile, all physicians must consider the potential longer-term implications for their patients, when making treatment choices,” he said.

Investigate thoroughly—we have an earnest responsibility to inform and provide counsel to the patients we serve

Michael D Dake (University of Arizona, Tucson, USA and secretary of the SIR Executive Council) said: “The finding that paclitaxel-coated devices used in the femoropopliteal arteries of patients with peripheral arterial disease are associated with an increased risk of death after one year is surprising and clearly unanticipated. The most important response to this unexpected report is: why? In the absence of patientlevel data from the randomised trials included in the meta-analysis, we are left grasping for explanations as to potential correlations and possible aetiological theories behind the stunning increase in all-cause death at two and five years in patients treated with paclitaxel-coated balloons and stents. The only sensible response is to join the authors’ concluding plea to support further investigations. These follow-up studies must include not only evaluations of the cause of death in the existing studies, but a thorough review of the meta-analysis methodology employed by the authors.

Whenever shocking revelations challenge consensual understanding—especially when the unexpected reports concern serious issues of patient safety—the medical and regulatory communities have an obligation to move expeditiously in a coordinated manner to investigate the findings thoroughly and an earnest responsibility to inform and provide counsel to the patients we serve.”

Seeking a plausible mechanism for a possible link between the drug and mortality remote from the procedure

Gary Ansel (OhioHealth Heart and Vascular Physicians, Columbus, USA) told Vascular News: “As a physician and a scientist, I take patient safety very seriously. The authors certainly raise an important question using a meta-analysis in an attempt to link mortality rates to drug toxicity. The meta-analysis is handicapped by lack of patient-level data. Having been an investigator on many non-drug-based trials, it is curious that this association is being made with mortality rates that are very similar to those of the non-drug based technology trials (i.e., bare metal stents, control arms, uncoated percutaneous transluminal angioplasty). The current authors want an ‘urgent’ closer scrutiny of the devices included in the meta-analysis. Having presented on these devices to the Centers for Medicare and Medicaid Services (CMS) and the US Food and Drug Administration (FDA) I know that these agencies and the sponsors who develop and sponsor these technologies (i.e., Cook Medical, Medtronic and other companies) also take patient safety very seriously.

I am somewhat surprised that the authors seem to ignore that an independent Clinical Events Committee reviewed all of the deaths in the IN.PACT SFA at the two-year follow-up point and found no link with the use of the paclitaxel-coated drug-coated balloon. As co-national principal investigator for the ZILVER PTX drug-eluting stent trial, a similar process was used for all patient deaths at five years. The authors also do not offer any plausible mechanism for a possible link between the drug and

Peter Schneider

mortality remote from the procedure. This underscores the importance of sponsors publishing the entirety of their data, at all follow-up periods, and making patient-level data available for independent analyses. These types of efforts should continue to have us look at long-term patient-level results for our procedures and I hope that the close evaluation will be the rule and not the exception.”

A statistical observation which generates important questions, not an answer

Peter Schneider (Kaiser Permanente, Honolulu, USA) stated: “The recent meta-analysis associating paclitaxel with late mortality yields a statistical observation. In my opinion, there is a mismatch between the available data and the conclusion. The study generates several important questions but does not propose a mechanism and does not provide a definitive answer.

“The following factors should be carefully considered as we analyse this study. All reported mortality data in superficial femoral-popliteal DCB and drug-eluting stent (DES) studies are within the range of reported results for mortality in other vascular device trials and expected results from population-based studies of peripheral arterial disease patients. The meta-analysis assumes that paclitaxel is present for the length of patient follow-up, and there is much evidence that contradicts this assumption. Some of the data from studies included in the meta-analysis are inferred from the published papers, rather than actual event numbers. It combines DCB and DES data to assess mortality, but this is probably not scientifically valid based upon the very different preparation and mechanism of delivery between DCB and DES. “Only three studies have extended to five years and would be potentially reliable sources for information on long-term mortality. Although the paclitaxel treatment groups (DCB and DES) are garnering a lot of attention, we must also look at the angioplasty (PTA) control groups. The PTA groups are small at five years and none of the studies were powered to evaluate mortality, especially long-term mortality; 109 patients for DCB (IN.PACT and THUNDER) and 121 patients for DES (ZILVER PTX). By chance, the PTA group in IN.PACT had among the lowest mortality ever reported in a vascular study. The PTA group in THUNDER had 46% lost to follow-up. It is not clear whether PTA groups were followed with the same tenacity as the paclitaxel groups, especially after a patency end point was reached, and this happened significantly more often in the PTA groups than in the paclitaxel treatment groups. Another possibility that needs investigation is whether PTA patients, who underwent many more target lesion revascularisations, also received better medical management in association with more frequent encounters? When deaths were adjudicated by clinical events committees, as in the IN.PACT and ZILVER PTX trials, there was no clustering around any particular cause or timeline.

“In summary, we have a mathematical observation based upon heterogeneous data that prompts many questions but does not answer any.”

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Drug-eluting devices

Longer-term, patient-level data needed before determining the fate of paclitaxel-coated devices Thomas Zeller Comment & Analysis The Katsanos et al meta-analysis reports an increased risk of mortality beyond one year across randomised studies of paclitaxelcoated balloons (DCB) and paclitaxel-eluting stents (DES). These observations are of great interest to the vascular specialist community. Even if these results are indeed alarming, as they suggest a paclitaxel-related excess mortality for patients with femoropopliteal artery disease, these findings must be interpreted with caution before the use of DCB and DES—which are the most effective interventional tools to date for femoropopliteal artery revascularisation—is discouraged.

I AM CONCERNED with the conclusion that there is an association between all-cause mortality and paclitaxel with no clear causal explanation of a pathophysiological mechanism of action. The authors spend no time exploring other potential hypotheses for the observed trends and the lack of patient-level data is a clear limitation to being able to draw these

conclusions. As one of the investigators in several of the studies cited here— in particular of those with five-year follow-up (THUNDER, IN.PACT SFA randomised controlled trial, ZILVER PTX randomised controlled trial)—it is important to note that the observed trend is not new. In fact, we published two- and three-year results showing a statistically significant frequency of all-cause

mortality between DCB and plain balloon angioplasty arms of the IN.PACT SFA study. We have subsequently presented on the four- and five-year data, showing no significant difference in mortality.

Events in the trial were reviewed by an independent Clinical Events Committee and none were related to the device, or paclitaxel.

Clinical pharmacokinetic data of paclitaxel-releasing DCB and DES demonstrated that detectable systemic exposure does not persist longer than a month before drug elimination drives blood concentrations below the level of detection (usually within a couple of weeks). In such circumstances, it is difficult to conceive of a scenario where such drug levels could produce severe and significant systemic events.

For readers not versed in statistical models and meta-analysis, the authors do not take the time to explain the assumptions that went into the analysis nor the assumptions for the equation.

For example, the equation suggests that the input dose of paclitaxel persists at the same rate over time. This is clearly inaccurate, as the authors stated paclitaxel is detectable only for weeks to months.

If the authors looked at randomised

BASIL-3 and SWEDEPAD trials paused for review of paclitaxel meta-analysis data The findings published by Konstantinos Katsanos and colleagues in JAHA quickly sparked wide-spread debate across the vascular community, as the meta-analysis’ implications and questions raised for use of paclitaxel-coated devices are discussed. The data had a nearimmediate impact on practice, as the SWEDEPAD 1 and 2 trials stopped enrolment within days of the publication. Shortly thereafter, the BASIL-3 trial similarly paused recruitment, stating there were concerns about patient safety following the outcomes of the metaanalysis of randomised controlled trials using paclitaxel treatments.

SWEDEPAD

The halted trials were aiming to evaluate various paclitaxel devices for patients with peripheral arterial disease. The SWEDEPAD (Swedish drug-elution trial in peripheral arterial disease) project is designed to test the hypothesis that drug-eluting technology is superior to conventional endovascular treatment in terms of important clinical outcomes, when applied on infrainguinal (femoropopliteal and/or infrapopliteal) obstructive vascular lesions. The SWEDEPAD project consists of two separate parallel studies, SWEDEPAD 1 and SWEDEPAD 2, each defined by the severity of peripheral arterial disease. As noted on clinicaltrials.gov, “patients with critical limb ischaemia are allocated to SWEDEPAD 1 and patients with intermittent claudication are allocated to SWEDEPAD 2.” SWEDEPAD 1 has a planned enrolment of 2,400 patients and SWEDEPAD 2 of 1,333 patients.

An update on the trial website states there is currently a “temporary haltof recruitement” to both trials. The statement reads: “Following the recent publication of a meta-analysis by Katsanos et al, the SWEDEPAD data safety and management committee (DSMC) did an interim safety analysis of SWEDEPADs prespecified safety variables. The results of the metaanalysis, and of our own interim safety analysis, prompted us to on

December 10, 2018 temporarily halt recruitment of patients to SWEDEPAD 1 and 2.

“We are now conducting a thorough in-depth analysis of all patients randomised in SWEDEPAD 1 and 2 with respect to this safety warning. This will require additional data and it is therefore decided to prolong the temporary halt of inclusions at least until early February 2019.”

To date, SWEDEPAD 1 has randomised 1,480 patients and 810 have been randomised in SWEDEPAD 2.

Recruitment halt follows steady decline in BASIL-3 enrolment rates BASIL-3 had already been experiencing difficulties with recruitment, and investigators struggled to reach their enrolment milestone targets throughout. At the Vascular Societies’ Annual Scientific Meeting 2018 (VSASM; 28–30 November, Glasgow, UK), BASIL lead investigator Andrew Bradbury (Heart of England NHS Foundation Trust in Birmingham, UK) warned of difficulties with enrolling patients to the study, saying he was “rather worried about BASIL-3”. Bradbury called on the community of vascular and endovascular surgeons to “explore why it has become difficult to recruit to a trial that actually should be pretty easy— three endo options in a very common procedure, and a very big patient population”.

controlled trials of non-drug-eluting endovascular devices trials, they would find a similar trend in mortality, showing an increased mortality rate in the active comparator arm of these trials.

Importantly, the mortality rates observed in the paclitaxel device trials are consistent with rates reported in epidemiological studies of peripheral arterial disease patients and in populations outside the clinical trial setting. Therefore, I question the leap to an association between paclitaxel and mortality. This likely reflects the natural progression of disease in these patients, who are known to present with concomitant comorbidities.

Finally, the authors do not differentiate between continents (America, Europe and Asia). Local differences in clinical follow-up programmes may also drive differences in all-cause mortality.

This meta-analysis highlights the need for additional long-term and patient-level data. Without this, the Katsanos et al conclusion is premature.

Thomas Zeller, UniversitaetsHerzzentrum, Bad Krozingen, Germany, is also a member of the Charing Cross Symposium Peripheral Arterial Executive Board.

The research is a joint initiative from University Hospitals Birmingham, the University of Birmingham Clinical Trials Unit (BCTU), and the National Institute for Health Research (NIHR).

“It should be an easy trial, really, because lots and lots of people have femoropop-endo for critical limb ischaemia and, from a patient experience point of view, the three arms are virtually identical,” he said. “We started at the beginning recruiting ahead of target, so why things have fallen off quite so badly in recent times is kind of difficult to understand.”

BASIL-2 is randomising patients with critical limb ischaemia who require infrapopliteal intervention either to vein bypass first or best endovascular treatment first.

“Best endovascular treatment can be whatever it is you want to use,” said Bradbury.

Meanwhile, the BASIL-3 trial has no surgical arm.

Participants are patients receiving femoropopliteal intervention for critical limb ischaemia and for whom it has already been decided that they will receive endovascular treatment rather than a bypass. They are randomised to either percutaneous transluminal angioplasty with a bailout bare metal stent (BMS), angioplasty with a paclitaxel drug-coated balloon (DCB) with or without a BMS, or to a paclitaxel drug-eluting stent with or without a BMS. The original target for BASIL 3 was 861 patients.

Three years after enrolment began investigators have now randomised 407 patients, less than 50% of the desired amount. Before the newly published data raised questions about paclitaxel treatments and caused the BASIL-3 enrolment to be put on hold, Bradbury acknowledged: “[Patient numbers were] quite a long way below what we had hoped for [for some months], but nevertheless pretty steady. But, since the summer, there has been a bit of a fall off. We have almost stopped recruiting to this trial, and I am not quite sure why that is. But it is quite a big problem, and I do not think any of us really want this to happen to the BASIL trial.”

10

Jan

Lutonix BTK randomised trial meets safety and efficacy endpoints at six months

Six-month outcomes of a multicentre randomised controlled trial using the Lutonix 014 drug-coated balloon (BD; DCB) has demonstrated the DCB is safe to use in peripheral lower limbs, below the knee. The primary safety endpoint of freedom from major adverse limb events and all-cause perioperative death at 30 days was met, and a Kaplan-Meier analysis indicated “no significant difference” in safety between the DCB and the plain percutaneous transluminal angioplasty (PTA) arms of the study.

T

he data were presented at the Vascular Interventional Advances annual conference (VIVA; 5–8 November, Las Vegas, USA) by Jihad Mustapha of Advanced Cardiac and Vascular Amputation Centers, Grand Rapids, USA. Mustapha said the study provided the “largest randomised controlled dataset on DCB versus PTA that is available to us as of today”, adding, “This is the first level 1 endovascular therapy treatment involving a multicentre, blinded randomised BTK trial.”

The clinical study is a prospective, global, multicentre randomised controlled trial comparing the Lutonix 014 DCB to standard angioplasty for the treatment of narrowed or obstructed arteries below the knee. The study used both proportional/binary and Kaplan-Meier analyses to assess safety and efficacy. The primary safety endpoint—freedom from composite all-cause death, above ankle amputation or major reintervention of the treated limb through 30 days—was met showing statistically significant safety equivalence between the Lutonix 014 DCB and standard PTA catheter, in both the proportional/binary and Kaplan-Meier analyses.

Mustapha expressed his hopes for the impact of these data, and excitement about the outcomes, stating: “The six-month clinical data from the Lutonix BTK

trial represent the beginning of a paradigm shift in the treatment of patients with critical limb ischaemia (CLI).

The initial results are extremely encouraging and give new hope to patients with CLI.” “Previously published DCB BTK trials have generated concern,” Mustapha said, “regarding amputation rates with DCB use—this is why we looked beyond 30 days, and saw no difference in primary safety at six months between DCB and PTA. The numbers were very close: 97% vs. 95%.”

The primary efficacy endpoint was assessed using a composite measurement of freedom from target limb

Patients with belowthe-knee critical limb ischaemia are the most complex subset of peripheral arterial disease in general.

occlusion, above ankle amputation, and clinically driven target lesion revascularisation, to define primary patency.

Proportional/binary analysis revealed an improvement in primary efficacy of 10.2% (DCB: 73.7% and PTA: 63.5%, p=0.0273, not-significant) at six months. The more commonly used Kaplan Meier analysis of the primary efficacy endpoint demonstrated a significant difference of 14.6% (DCB: 85.3% and PTA: 70.7%, p<0.001). Additional analyses are planned for 12-, 24and 36-month follow-ups.

The trial included 442 participants of which 91% had CLI. “Patients with BTK CLI are the most complex subset of peripheral arterial disease in general,” Mustapha said, highlighting the high rates of amputation estimated at around 25–33%, and an approximate US$95 billion cost in the USA per year to treat this patient population.

The amputation rate specific to each arm of the study was not available at the time of presenting, however Mustapha emphasised the notably low overall rate of amputation, comparing the 3.8% figure at six months to double-digit rates in previous trials. “We did not see any increased rate of amputation in the DCB arm,” Mustapha clarified, “but in general actually the number of amputations was less than 4% in the entire cohort— PTA and DCB.” At baseline, 71% of all patients enrolled had diabetes, 92% had hypertension and close to 60% of patients were smokers. Within the 91% with CLI, the majority were Rutherford category four and five. Addressing baseline demographic risk factors, Mustapha noted that Rutherford categories were balanced across both arms, however the DCB arm had 40% more TASC C and D lesions than the PTA group, and mean lesion length was longer.

Mustapha suggested it is important to note that this is the first global randomised trial to demonstrate safety of a DCB in BTK use, as “generally, in this very sick patient population, with an extremely challenging vascular bed, it is important to put this safety issue to rest: to know that you can use DCB in these severely diseased patients.”

DEEPER first-in-human results find the Temporary Spur stent safe The first-in-human data from the DEEPER trial were presented at VIVA 2018 (5–8 November, Las Vegas, USA) by John Laird, Adventist Heart & Vascular Institute team at St Helena Hospital, USA. This early clinical experience yielded promising results in a high-risk patient population.

THE PURPOSE OF this trial was to evaluate the safety and efficacy of the Temporary Spur stent system (Reflow Medical), in conjunction with a drugcoated balloon (DCB) in patients with below-the-knee disease. The primary efficacy endpoint of the trial was binary arterial flow of treated lesion sites by continuous wave Doppler through six months. The dual primary safety endpoints were freedom from deviceand procedure-related death through 30 days post-procedure and freedom from target limb major amputation and clinically driven target lesion revascularisation through 12 months post-procedure.

The DEEPER trial is a nonrandomised feasibility trial; it is a prospective single centre, single arm study. Trial enrolment began in October 2017 and was completed in May 2018, with 21 patients having completed trial and procedure enrolment and undergoing follow-up. Twelve patients have completed follow-up through six months, and all 21 have completed follow-up out to at least three months.

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Late-breaking trials

Laird reported that all 21 enrolled patients have met the safety endpoints of the trial to this date, with no clinically driven target lesion revascularisation, no major adverse limb events, and freedom from device- and procedure-related death through 30 days post-procedure.

Out of the group that has completed six-month follow-up, 11 patients (92%) were found to have patent flow by waveform Doppler through six months, the primary efficacy endpoint, confirmed by ultrasound/angiogram for Spur/DCB-treated areas. Adjudication of the Doppler ultrasound results and angiographic follow-up results have been conducted with Core Lab. The majority of patients in this trial have seen an improvement in clinical outcomes, with an average decrease in Rutherford class score by two classes (with a maximum reduction of four classes) at six months. Of patients with wounds, 88% saw complete wound healing at six months and all saw improvement.

The temporary SPUR stent system is designed to overcome some of the

challenges presented by below-theknee lesions. The device is a novel, self-expanding, radiopaque nitinol frame with an open lumen, and can be unsheathed in the vessel and expanded, left in place as long as necessary, and then recovered and removed. It has calcification and artery penetrating spurs (hence the name), which are 1.5mm in length, with a diameter smaller than a 35-gauge needle. The stent currently comes in two sizes: 3mm diameter and a 50mm long device, and a 4mm diameter and 60mm long device.

The concept underpinning these calcification or artery penetrating spurs is that they act to enhance drug uptake into the deep vessel wall elements, and allow for greater and more effective prevention of restenosis. Laird explains that “the ultimate plan will be to have a drug-eluting SPUR device”, but added that “for the DEEPER trial we looked at the concept of SPUR followed by drugcoated balloon.”

Regarding future work, Laird expanded, “We will see additional follow-up of the DEEPER trial patients,

all 21 of them out to one year, and then continue validation of this technology with the DEEPER OUS [outside of the USA] trial, which will begin in 2019.

This will be a 100-patient trial with spur, followed by drug-coated balloon angioplasty taking place at four sites in New Zealand and Europe, and there will be further device design iterations, including ultimately a drug-eluting version of the SPUR temporary stent.”

Ramon Varcoe, of the Department of Surgery and The Vascular Institute at Prince of Wales Hospital and the University of New South Wales in Sydney, Australia, said immediately after the talk that the trial had produced some “really interesting data”, adding, “I have never seen a device like that before”.

Fielding questions from the panellists at VIVA, Laird responded to a query about the stent’s potential use without a subsequent drug-coated balloon angioplasty: “We have not done a significant number of cases without the drug-coated balloon, but I think there is every reason to think that it could be an effective standalone treatment. I think you do have to dilate the device to get it fully expanded and to get those spurs fully embedded into the vessel, but having that temporary stent platform I think gives you a good chance of having a good angiographic result with less elastic recoil, partly because of the stent, but also due to those penetrating spurs which can deal with that medial canal stenosis which is so often present.”

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Jan

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Medical device innovation

US FDA plan shakeup of its 510(k) clearance programme The US FDA has announced plans to modernise its 510(k) clearance programme for approving medical devices for the US market. Data show that about 20% of current 510(k) devices are approved on trials that compare novel devices to predicate devices that are more than 10 years old. With its revised programme, the agency wants to ensure medical devices coming to market account for advances in technology or demonstrate that they meet more modern safety and performance. The announced changes follow a report from the International Consortium of Investigative Journalists (ICIJ) that heavily criticises how medical devices are approved for use.

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nder the existing 510(k) clearance programme, a medical device can be approved for market if (according to a study) it shows comparable safety and efficacy to a similar device that is already on the market. However, a limitation of this programme is that a substantial amount of devices (20%) are compared with devices (or predicates) that are more than 10 years old. In a statement, Scott Gottlieb (FDA commissioner) and Jeff Shuren (director of the Center for Devices and Radiological Health) comment: “Older predicates might not closely reflect modern technology embedded in new devices, or our more current understanding of device benefits and risks”. They stress that they are not suggesting these older devices, or the devices that are compared to them, are unsafe but note “we believe encouraging product developers to use more modern predicates would give patients and their doctors a choice among older and newer versions of the same type of device, promote greater competition to adopt modern features that improve safety and performance, and help make sure that newer devices reflect more modern technology and standards that can improve patient care and outcomes”.

Therefore, the FDA is proposing to list devices on its website that have demonstrated substantial equivalence to older predicate devices, with predicates that are more than 10 years old as a starting point. However, before going ahead with this plan, Gottleib and Shuren state that the agency is seeking public feedback on “whether we should make public those devices or those manufacturers who make technology that rely on predicates that are more than 10 years old, whether other criteria should inform our point of reference, and whether there are other actions we should take to promote the use of more modern predicates”.

Additionally, early next year, the FDA intends to finalise guidance establishing an alternative 510(k) pathway that will allow manufacturers of certain wellunderstood device types to rely on objective safety and performance criteria to demonstrate substantial equivalence as a way to make the pathway more efficient and to adopt modern criteria as the basis for the predicates that are used to support new products.

“We are planning to rename this new approach the ‘Safety and Performance Based Pathway’ to reflect its focus on advancing improved safety and performance of new products. Through this new path, a company would demonstrate a novel device meets modern performance-based criteria that have been established or recognised by the FDA and reflect current technological principles,” Gottleib and Shuren comment. They add that “eventually” they would like this new pathway to replace the practice of comparing a new device to “a specific and, sometimes old, predicate device”.

As well as announcing the changes to the 510(k)

Scott Gottlieb

clearance programme, in their statement, Gottleib and Shuren highlight the work that the Center for Devices and Radiological Health (CDRH), a subset of the FDA, has done (since 2009) to eliminate the use of the 510(k)-cleared predicates when the devices have raised safety concerns that “warrant treating them as highrisk technologies”. They explain that through a process called “up-classifying”, the FDA relabels such a device as “Class III”—meaning it requires premarket approval, “the most stringent review pathway”, before it can remain on the market.

After discussing other proposed revisions, Gottleib and Shuren conclude their statement by saying: “We are proud of the work CDRH staff are doing to make sure that the devices we regulate are safe. We will continue to take new actions to strengthen the device programme for years to come.”

Report heavily criticises medical device industry

A few days prior to the FDA announcing its changes to the 510(k) programme, the ICIJ published deeply critical report of the medical device industry. The report—the result of a year-long investigation by the ICIJ—highlights several case examples of patients being harmed by medical devices (from a mesh implant to treat incontinence to implantable cardioverter defibrillators). It claims that the medical device industry may be “unnecessarily putting millions of patients at risk of serious harm in its quest for profit”, calling into question how devices are regulated and approved for market. According to the report, governments in “dozens of countries” in Africa, South America, and Asia “do not regulate medical devices at all, instead placing

their trust in European authorities or in the US FDA”.

Furthermore, while the report acknowledges that the FDA “is generally considered to provide more robust oversight than any other heath agency in the world”, it states “even that oversight is lacking, with complex devices approved too quickly by American authorities and troublesome ones not pulled from hospital shelves fast enough, patient advocates and health experts say”.

At present, there is not a global resource for recalls and safety notices; therefore, to address this issue, the ICIJ has built the International Medical Devices Database. The report explains the database “gathers recalls, safety alerts and field safety notices (more than 70,000 from 11 countries) to create a searchable portal that anyone can access to help discover whether a device was flagged for official safety concern”. It adds the database shows that, over the past decade, there have been “more than 2,100 ‘Class I’ recalls in the USA for defects deemed to pose a ‘reasonable chance’ of ‘serious health problems or death’”. “Some of these could be addressed easily, with a quick software update or change of wording in the instructions, while others involved devices implanted in millions of patients that spurred thousands of surgical removals,” the report comments.

Responding to the ICIJ report, the Advanced Medical Technology Association (AdvaMed)—the foremost US trade group for the device industry—accuses it of “magnifying the stories of only a few individuals” and, thus, overlooks the “overwhelming positive experiences of millions of others”. “We take seriously all reports of patient impact, and though the medical community can never completely eliminate risk, we always strive to improve our technologies and delivery care,” the AdvaMed statement adds.

Complex devices [are] approved too quickly by American authorities and troublesome ones not pulled from hospital shelves fast enough, patient advocates and health experts say.

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Drug-eluting stents

VMI-CFA trial challenges old mantra of “no endovascular therapy” for common femoral artery The one-year findings from the VMI-CFA study of the use of the Supera stent (Abbott Vascular) in the treatment of common femoral artery stenosis or occlusion have shown high patency and freedom from target lesion revascularisation, challenging the traditional endarterectomy only approach.

THE RESULTS WERE presented by Koen Deloose (AZ Sint Blasius, Dendermonde, Belgium) at the Vascular Interventional Advances meeting (VIVA; 5–8 November, Las Vegas, USA). Deloose maintained that his presentation of the full cohort (100 patients) 12-month results of the VMI-CFA trial provided “the ultimate proof of efficient and safe common femoral artery endovascular treatment”.

He indicated that, among vascular surgeons, the common femoral artery remains one of the last areas of open reconstructive surgery. “They often say that there should be no endovascular therapy for this baby, and there are good arguments in support of such ‘near-religion’.

First of all, it is a high flexion zone, there are superb longterm surgical patencies and the surgery is easy and safe to perform and easily accessible,” he said.

On the other hand, he added, disease in the common femoral artery is bulky, eccentric and heavily calcified, the location is prone to crushing, and the groin is an important access area for surgery and future endovascular treatment.

Deloose rebutted many of these claims, indicating that some of them were untrue. He showed data which found that the common femoral artery is “not at all a flexion zone, but a very fixed and stable segment”.

While he agreed that the common femoral artery is associated with bulky, eccentric, heavily calcified plaque and is prone to crushing, he pointed to the endovascular tools that exist today that can address these challenges.

He mentioned specifically the Supera stent which, in his experience, is able to create a circumferential, open vessel at the end of the procedure. Conventional standard, nitinol stents, on the other hand, he said, have a much lower crush resistance. As for future femoral access, Deloose explained that there is no problem in re-puncturing an implanted Supera stent to gain femoral access.

In the majority of cases, he maintained, the common femoral artery area is ripe for a tailored endovascular penetration as already proven in the TECCO trial, which looked at surgery versus stenting for the treatment of common femoral artery atherosclerotic lesions and

found no difference in terms of efficacy, patency and freedom from target lesion revascularisation between the two groups, but the mortality and morbidity rate told a different story, where the investigators observed a clear advantage in the endovascular group.

While the TECCO study included a variety of devices and diseases, Deloose explained that the VMI-CFA trial is a prospective, multicentre, single arm trial to evaluate the Supera stent for the treatment of symptomatic (Rutherford 2–4) common femoral artery disease. One hundred patients have been enrolled at seven centres in Europe. The primary efficacy endpoint is primary patency at 12 months in the common femoral artery with no reintervention, and the primary safety endpoint is periprocedural adverse events up to 30 days postprocedure. Secondary endpoints include technical success rate, primary patency at six months, freedom from TLR at six and 12 months, clinical success and safety profile up to one year.

Inclusion criteria meant that only patients with Rutherford 2–4, de novo or post plain balloon angioplasty (POBA) lesions, stenosis >50%/occlusions, patent deep femoral artery and good superficial femoral artery run off were enrolled in the trial.

Out of the 100 patients enrolled, 81% were male and one-third of them were diabetic. Further, 79 patients were claudicant and 21 had critical limb ischaemia. Lesion length was 44.17mm (15–80mm; ±15.67mm), reference vessel diameter was 7.29mm (5mm–9mm; ±0.93mm), and degree of stenosis was 82.6%. Occlusion occurred in 11% and there were 82 calcified lesions.

Deloose reported that all the procedures were technically successful, with no more than 30% residual stenosis at the end of the procedure. “As you know, if you want to implant a Supera stent, vessel prep is essential—predilatation was performed in all of the cases and postdilatation was performed in 83% of the cases,” he explained.

After one year, Deloose reported that the primary patency in the full cohort of patients was 95.2%, core lab adjudicated. Freedom from target lesion revascularisation

was 97.8%, survival was 91.8%, and freedom from target vessel revascularisation 92.6%.

“Looking at clinical outcome, we see a tremendous shift in Rutherford Becker classification from 2, 3 and 4 to 0 and 1. In terms of safety, the procedure was completely safe at 30 days, with no events, and only two clinically-driven target lesion revascularisations at one year,” he said.

Deloose concluded, “Although common femoral endarterectomy still remains the gold standard, the historical ‘no endovascular for this baby’ statement is wrong. There are some indicative papers that show that there is definitely a place for safer and as-efficient endovascular therapy in common femoral artery treatment. Newer generation devices, like the high crush resistant, repuncturable Supera stent, are facilitating this endovascular approach.”

He added that the VMI-CFA trial, using the Supera stent, shows “excellent” one-year results and that a head-to-head randomised controlled trial of Supera versus endarterectomy seems to be a logical sequence to definitely clarify the common femoral artery treatment discussion.

Speaking about the potential of setting up a randomised controlled trial, Deloose tells Vascular News: “Now, actually, we are comparing apples with oranges—I want to compare apples with apples. So if we set up a randomised controlled trial of surgery versus Supera in the CFA , we will really have a headto-head comparison between two different techniques: an endovascular one and a surgical one, with the same assessment methods, the same approaches. This is the only way to prove which one is the best.”

“The minimally invasive character of the endovascular treatment is clearly the most important benefit. Patients stay one to two days in the hospital, no incision, no wound complications and return to work and daily activities is very fast. All advantages compared to open surgery. The goal of a randomised controlled trial would be to prove this superiority in terms of safety and the noninferiority in terms of efficacy.”

Meta-analysis suggests Supera has advantages over drug-eluting stents for superficial femoral artery lesions

Data from an all-comers parametric survival analysis indicate that the mean duration of freedom from restenosis is greater in patients who received the Supera bare metal stent (Abbott) for the treatment of a superficial femoral lesion than those who received a drug-eluting stent.

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peaking at 2018 VEITHsymposium (13–17 November, New York, USA), Konstantinos Katsanos (School of Medicine, Patras University Hospital, Patras, Greece) reported that the 2017 European Society of Cardiology (ESC)/European Society for Vascular Surgery (ESVS) guidelines for vascular surgery recommend an “endovascular” first approach for the management of femoropopliteal lesions. He added while these guidelines say primary stent implantation “should be considered” for such lesions, they only state that drug-coated balloons or stents “may be

considered” in this context. According to Katsanos, these recommendations relate to the amount of data available.

The present meta-analysis was performed because comparison data for devices for femoropopliteal lesions are limited. Katsanos commented that he and his colleagues, in a previous meta-analysis, found that longer-term outcomes were better with paclitaxelcoated balloons and paclitaxel-eluting stents than with covered stents, but he noted that “some devices, such as Supera, were not covered” in the study.

Therefore, in this meta-analysis, they

compared data for Supera with that for the Zilver PTX paclitaxel-eluting stent (Cook Medical) and the Viabahn covered stent (Cook Medical). Furthermore, Katsanos et al looked at evidence from both randomised controlled trials and from real-world studies “to provide more generalisable results” than they would have done if they had just looked at randomised controlled trial data.

The primary endpoint of the resultant “broad systematic review and metaanalysis” was freedom from restenosis (aka primary patency) and the secondary endpoint was freedom from target lesion

revascularisation.

After reviewing information from Medline, Scopus, and archived online material, the investigators identified 20 studies for Supera (2,341 limbs analysed), 17 studies for Zilver PTX (4,263 limbs), and 28 studies for Viabahn (1,914 limbs analysed). However, Katsanos said the study was “still a work in progress” and would include percutaneous transluminal angioplasty and drug-coated balloon in the future.

The investigators found that at five years, primary patency appeared to be increased with Supera vs. Zilver PTX and Viabahn; primary patency appeared to be greater with Ziver PTX vs.

Viabahn. Additionally, median patency— or the average point at which restenosis occurred—was greater with Supera: 49 months vs. 32 months for Zilver PTX vs.

22 months with Viabahn.

“Supera seems to perform better than drug-eluting stents, but patency rates vary on covariates. Future studies should include nitinol stents and drug-coated balloons,” Katsanos concluded.

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Critical limb ischaemia

Draft Global Vascular Guidelines for chronic limb threatening ischaemia published online The European Society for Vascular Surgery (ESVS), Society for Vascular Surgery (SVS), and the World Federation of Vascular Societies (WFVS) have come together to produce draft guidelines on the management of chronic limb threatening ischaemia (CLTI). The guidelines, which are published on the SVS website and were open for stakeholder comment until 7 December 2018, aim to establish a new patientcentred, evidenced-based framework for clinical decision-making for patients with CLTI.

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s reported in Issue 76 of Vascular News (November 2017), Florian Dick (University of Bern, Bern, Switzerland) gave a preliminary overview of the new guidelines at the 2017 ESVS meeting (19–22 September, Lyon, France).

However, they were not available for public comment until late November 2018. During the consultation period, the SVS website stated: “Anyone is welcome to review the draft guidelines and provide comments, including members of the sponsoring societies, other clinicians who are directly involved in the management of patients with CLTI, referring providers and allied professionals who care for the at-risk population, industry and insurance companies, researchers, patients, caregivers, and members of the public.”

Notably, the draft guidelines use the term “chronic limb threatening” to describe limb ischaemia rather than “critical limb” or “severe limb”.

Guideline authors Michael S Conte (Division of Vascular and Endovascular Surgery, Department of Surgery, and Cardiovascular Research Institute, UCSF, San Francisco, USA) and colleagues write in the online document that CLTI denotes “the universe of patients with advanced lower limb ischaemia, wounds, neuropathy, and infection, and who are commonly referred to vascular specialists for evaluation and management”. They add that critical ischaemia and severe ischaemia “connotes specific haemodynamic thresholds and fail to recognise the full spectrum and inter-relatedness of components beyond ischaemia that contribute to major limb amputation and/or long-term disability”.

The importance of staging the degree of limb threat across this broad spectrum of presentations is stressed in the document, and the SVS threatened limb classification system (based on grading wound, ischemia, and foot infection or “WIfI”) is recommended for standard use and further prospective validation.

When it comes to revascularisation for CLTI, a critical concept in the guideline is to structure decision making around patient risk, limb severity, and anatomic

Anyone is welcome to review the draft guidelines and provide comments.

Michael Conte

complexity—“PLAN”—of disease (in that order). This is considered as a central step forward towards evidence-based revascularisation. Patient-risk estimation for both perioperative (30 day) and longterm (two-year) survival is an important step, with “high risk” defined as expected perioperative mortality >5% or two-year survival <50%.

Another key element of the guidelines is a new anatomical staging system for assessing CLTI—the global anatomic staging system or “GLASS”. Speaking at VEITHsymposium 2018 (13–17 November, New York, USA), Conte reported that a new approach to assessing CTLI was needed because existing approaches were “inadequate”. He said: “Schemes focused on individual lesions (e.g. TASC) or the overall burden of disease (e.g. Bollinger) are not useful for defining evidence-based revascularisation CTLI).” The primary anatomic goal of revascularisation in CLTI is to restore direct in-line flow to the ankle and foot.

Therefore, GLASS was developed as an integrated limb-based system rather than “lesion by lesion”. Importantly, Conte explained, GLASS is designed from an endovascular mindset to stage the overall anatomic complexity of disease into three categories based on estimated technical success and one-year limb-based patency.

Using a high-quality angiogram of the leg including ankle and foot, the treating physician identifies the preferred target artery pathway (TAP). Conte stated that the TAP usually involves the

least diseased part of the infrapopliteal artery or may be angiosome-based but added that the choice of the TAP is the “clinician’s decision”.

Once the TAP is selected, the femoropopliteal and infrapopliteal segments are assessed separately on a scale of 0 to 4. The grades are based on lesion characteristics including length, occlusion vs. stenosis, and location.

These two scores are then combined to find the overall GLASS stage (I,II, III) using a consensus-based matrix. For example, with the matrix, a patient with score of 4 in the femoropopliteal segment and a score of 2 in the infrapopliteal segment would, overall, be categorised as GLASS stage of III (high complexity disease). Conte commented that a GLASS stage III means “extensive femoropopliteal or infrapopliteal occlusions, alone or in combination with any disease in the other segment, and/or popliteal chronic total occlusion”. GLASS stages I and II mean, respectively, “short-intermediate length femoropopliteal disease and/ or short length infrapopliteal disease with no/minimal popliteal disease” and

“intermediate-long length femoropopliteal disease, may include popliteal stenosis, and/or short-intermediate length infrapopliteal disease”.

The guideline then describes preferred interventional approaches based on the PLAN matrix. For example, for an average risk patient with WIfi stage 2 limb and a GLASS stage of II, endovascular therapy would be the preferred initial approach. Open bypass with vein is recommended for average risk patients with GLASS stage III/WIfi stage 3 and GLASS stage III/ WIfi stage 4. Other intermediate combinations are within the grey area of equipoise of the writing group and data from clinical trials such as BESTCLI and BASIL-2,3 are awaited.

In the draft document, Conte et al say that the “the primary goal” of the guidelines “is to improve the quality of care for all patients with CLTI, as well as for those at risk for CLTI. An important secondary goal is to identify key research priorities in need of further basic, translational, clinical and/or health services investigation to advance those aims”.

GORE® VIABAHN® Endoprosthesis INDICATIONS FOR USE IN THE U.S.: The GORE® VIABAHN® Endoprosthesis is indicated for improving blood flow in patients with symptomatic peripheral arterial disease in superficial femoral artery de novo and restenotic lesions up to 270 mm in length with reference vessel diameters ranging from 4.0 – 7.5 mm, in superficial femoral artery in-stent restenotic lesions up to 270 mm in length with reference vessel diameters ranging from 4.0 – 6.5 mm, and in iliac artery lesions up to 80 mm in length with reference vessel diameters ranging from 4.0 – 12 mm. The GORE® VIABAHN® Endoprosthesis is also indicated for the treatment of stenosis or thrombotic occlusion at the venous anastomosis of synthetic arteriovenous (AV) access grafts.

CONTRAINDICATIONS The GORE® VIABAHN® Endoprosthesis with Heparin Bioactive Surface is contraindicated for noncompliant lesions where full expansion of an angioplasty balloon catheter was not achieved during pre-dilatation, or where lesions cannot be dilated sufficiently to allow passage of the delivery system.

Do not use the GORE® VIABAHN® Endoprosthesis with Heparin Bioactive Surface in patients with known hypersensitivity to heparin, including those patients who have had a previous incidence of Heparin-Induced Thrombocytopenia (HIT) type II. Refer to Instructions for Use at goremedical.com for a complete description of all warnings, precautions and adverse events.

Products listed may not be available in all markets.

GORE®, VIABAHN®, and designs are trademarks of W. L. Gore & Associates. ©2011, 2017, 2018 W. L. Gore & Associates, Inc. AQ0162-EN3 JANUARY 2018

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Fenestrated endovascular repair

“FEVAR necks do not seem to dilate” Michael P Jenkins (St Mary’s Hospital, Imperial College Healthcare NHS Trust, London, UK) told delegates at VEITHsymposium 2018 (13–17 November, New York, USA) that—based on early data from GLOBALSTAR II—significant neck dilatation does not appear to occur in patients who have undergone fenestrated endovascular aneurysm repair (FEVAR). He also noted that aortic neck dilatation occurs in about 25% of patients who undergo endovascular aneurysm repair (EVAR) and is one of the main causes of reintervention.

JENKINS COMMENTED: “When the EUROSTAR registry reported on reinterventions 17 years ago [showing a risk of late failure of 3% per year with EVAR], we all thought that reinterventions would go away in time. Yet, that has not been the case. If you look at the latest publications for EVAR, reinterventions are still there”.

He added that he suspected proximal neck remodelling, “i.e. aortic neck dilatation”, was one of the main reasons why reinterventions occur. “The jury is still out whether dilatation is a result of range of force from the device or dilatation of the native aorta itself.

But, I think it is a combination of both.

Either way, loss of the seal zone is what happens,” Jenkins observed.

He noted that “taking the seal zone more proximally with a fenestrated device” has been one of the approaches

used over the last 10 years to address this risk of loss of seal zone, adding that he hoped that the available data showed that this could be done “without an adverse effect on mortality or morbidity”.

Data from the GLOBALSTAR (British Society for endovascular therapy: Global collaborators on advanced stent graft techniques for aneurysm repair) registry has provide further support for FEVAR. “This was real-world data from 318 FEVAR implants in the UK. FEVAR was with a Zenith device (Cook Medical) and was associated with reasonable mortality and good three-year outcomes. But, this was at the cost of reinterventions,” Jenkins observed.

However, these data were only for implants performed between 2007 and 2010; a second iteration of GLOBASTAR (GLOBALSTAR II)

When the EUROSTAR registry reported on reinterventions 17 years ago, we all thought that they would go away in time.

Michael P Jenkins

reviewed implants performed up until 2017. He reported: “We aimed to look at available data for the original cohort and for all implants since then, using both FEVAR devices now available in the UK (Terumo Aortic’s Anaconda as well as the Zenith device). There was an increase in mortality [33 deaths at 30 days vs. 22 deaths at 30 days in the original cohort] and this does reflect a slightly more proximal neck in the

overall cohort being treated than the original cohort”. Furthermore, at five years, just two-thirds of patients were still alive. However, again, this was at the cost of reinterventions.

Additionally, Jenkins reviewed data for 42 patients enrolled from Imperial College (where he is based) who had a mean follow-up of 7.8 years. Comparing the latest available computed tomography (CT) scan with the CT that was taken immediately after the operation, he reviewed the median diameter change in three areas: 30mm proximal to stent struts (A); proximal Dacron edge (B); and distal end of lowest renal fenestration (C). During the follow-up period, the median change was +0.1mm (interquartile range [IQR] -1mm to +3.3mm) for “A”, +2.2mm (IQR +0.5mm to 4.8mm) for “B”, and 0.5mm (IQR 0.4mm to +4.4mm) for “C”. Overall, Jenkins noted, these findings show that “no significant aortic neck dilatation” had occurred.

He concluded: “It is well established that a proportion of EVAR seal zones are lost over time and this is more prevalent in ‘difficult necks’. FEVAR necks do not seem to dilate and early GlOBALSTAR II data are encouraging.”

Study finds increased risk of abdominal cancer associated with EVAR A population-based cohort study by Viknesh Sounderajah and colleagues at Imperial College in London, UK, found an increased risk of abdomincal cancer associated with endovascular anurysm repair—irrespective of whether or not CT surveillance was included in follow-up post-EVAR. Presenting the data at the Vascular Societies’ Annual Scientific Meeting (VSASM; 27–29 November, Glasgow, UK), Sounderajah commented the data “feeds in to the National Institute of Health and Care Excellence (NICE) abdominal aortic aneurysm guidelines debate.“

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he study included patients in England, UK, over the age of 50 who had received open or endovascular repair of an abdominal aortic aneurysm (AAA) between April 2005 and March 2013, in either elective or emergency setting, and who received a post-operative diagnosis of cancer.

“Over the last 10 to 15 years, endovascular aneurysm repair (EVAR) has supplanted open repair in many senses for the treatment of symptomatic and threshold aneurysms. As noted in well-known randomised controlled trials, EVAR is traditionally associated with short-term benefits with respect to mortality, morbidity and length of stay,” Sounderajah said at VSASM. “However,” he continued, “more contemporary data suggest that there is a catch-up in late mortality and increased risk of reintervention with respect to the EVAR group. Sounderajah explained there is a hypothesis that part of the late-stage mortality following EVAR may be due to malignancy burden—an idea which he says is “not often talked about.” The question posed in the study is whether exposure to external radiation from EVAR procedures or CT surveillance as part of the follow-up protocol contributes to abdominal cancerrelated mortality in abdominal aortic aneurysm patients receiving EVAR in comparison to open repair. Indeed, Sounderajah notes this hypothesis is in line with findings

of oncological studies examining radiotherapy-based treatment for breast cancer and lymphoma, “which shows that there are new instances of malignancy following radiotherapy treatment”.

The primary outcomes of the study were survival free from abdominal malignancy and death from abdominal malignancy, with the secondary outcomes of overall malignancy-free survival and freedom from lung and non-abdominal obesity related cancer. Sounderajah and colleagues also decided to perform a subgroup analysis, comparing patients who received CT scan surveillance on follow-up to those who did not. At baseline, EVAR patients were older (median 76 years versus median 73 years in the open repair arm) with significantly higher percentages of comorbidities.

“With regards to the cause of death”, Sounderajah said, “it is noted that 18% of patients who undergo EVAR succumb to cancer.” This is in comparison to 14.7% for the open repair. At seven years, an increase was found in the proportion of patients admitted with abdominal cancer or abdominal cancer as cause of death in the EVAR group (HR 1.14; 95% CI 1.03–1.27) as well as an increase in the proportion of patients admitted with any type of cancer or cancer as cause of death (HR 1.14; 95% CI 1.03–1.27). Furthermore, the subgroup analysis found no difference in the incidence of abdominal cancer

or abdominal cancer as cause of death in EVAR patients receiving CT surveillance or non-CT surveillance (HR 0.87; 95% CI 0.67–1.13; p=0.308).

Sounderajah concluded, “our study suggests there was an increased risk of abdominal malignancy associated with EVAR, irrespective of CT surveillance following the primary procedure. This is the first population-level study to assess this, however we do appreciate there are some limitations with respect to the observational design, confounders that we cannot account for with the dataset, the granularity of the dataset which is often binary in many cases, as well as an ascertainment bias—but we do hope this feeds into the current NICE guidance, as well as the radiation safety understanding.”

There was an increased risk of abdominal malignancy associated with EVAR, irrespective of CT surveillance.

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Using TEVAR to treat aortic dissection improves survival over open repair Thoracic endovascular aortic repair (TEVAR) demonstrates a oneand five-year survival advantage over the current “gold standard” practice of medical therapy in the treatment of uncomplicated type B aortic dissection, a recent study concludes. In light of these data, lead author James Iannuzzi (currently on staff at University of California San Francisco Medical Center, USA), senior author Virendra Patel (Division Chief of Vascular surgery at Columbia University Irving Medical Center, New York, USA) and colleagues call for a paradigm shift in the acute management of aortic dissection in favour of early TEVAR.

C

iting a paucity of data regarding the impact of acute treatment of uncomplicated type B aortic dissection on long-term survival in a real-world cohort, the study investigators set out to compare TEVAR to open repair and medical therapy.

In their retrospective analysis of a prospectively collected Californian administrative database analysing 9,165 acute uncomplicated type B aortic dissections, 76% of those treated with TEVAR survived to five years’ posttreatment, compared with an inferior five-year survival rate of 67% in open repair patients, and a survival rate of 60% for medical therapy recipients.

The authors hypothesise that the mechanism by which TEVAR may have a favourable impact on survival is “by covering the entry tear, leading to false lumen thrombosis and prevention of aneurysmal degeneration.” They go on to explain: “Evidence from complicated type B aortic dissections treated with TEVAR demonstrates 63% to 88% partial or complete false lumen thrombosis. TEVAR for complicated type B aortic dissection has also been associated with decreased aortic diameter; however, this remains controversial as it has not been demonstrated consistently. By prevention of aneurysmal degeneration, initiation of false lumen thrombosis, and prevention of recurrent dissection, TEVAR may improve long-term survival, as demonstrated in this study and others.”

Iannuzzi and colleagues conclude that TEVAR for uncomplicated type B aortic dissection is a relatively safe and effective approach, associated with longer survival, but note that further study is necessary to determine longer term outcomes for these patients.

Major complications were lower in TEVAR and medical therapy cases than for open repair, with 49% of patients treated with medical therapy experiencing a major complication, and 55% of TEVAR patients, compared to a major complication rate of 72% in open repair cases. Paraplegia rates were also similar between TEVAR and medical therapy (3.4% and 2.9%, respectively), but where found to be highest in the

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Thoracic endovascular repair

Virendra Patel

open repair group (9.3%).

Speaking to Vascular News about the clinical ramifications of this finding, Patel comments, “Medical therapy has historically been the gold standard in the management of uncomplicated acute type B aortic dissection, however this work and others call that strategy into question as TEVAR treated patients are associated with better long term survival.

This will not be a strategy to treat all patients; however, patients with excellent anatomy and young or healthy patients with expected long term survival should be considered for treatment in experienced centres or referral to aortic centres for TEVAR within the critical window of opportunity to stimulate beneficial remodelling, reduce late aortic events, and improve survival.”

Previous small, randomised controlled trials have found similar results. For

example, the Investigation of Stent Grafts in Aortic Dissection (INSTEAD) trial, which randomised patients to optimal medical therapy or TEVAR for treatment of subacute to chronic uncomplicated type B aortic dissection, did not demonstrate a survival benefit at one year (as published in the Journal of Thoracic Cardiovascular Surgery in 2010), but did find that patients treated with TEVAR had improved aortaspecific survival at five years’ follow up.

Iannuzzi and colleagues’ study included nearly four times as many TEVAR patients as the INSTEAD trial, and had concordant results.

Explaining the difference between the present study and the INSTEAD trial, the authors write: “A major difference between INSTEAD and this retrospective administrative study is timing of repair. The INSTEAD trial included healthier patients overall with a younger age (mean age of 60 years compared with 66 years), fewer diabetics (6% in INSTEAD vs. 12% in this study), and fewer smokers (17% in INSTEAD compared with 30% in this study). Whereas INSTEAD was a landmark study, corroboration in the real-world setting is imperative, and this study helps validate the INSTEAD findings that long-term survival is improved in patients treated with TEVAR.” A proponent of stenting more uncomplicated subacute dissections, interventional radiologist Darren Klass, Vancouver, Canada, told Vascular News: “Type B aortic dissection carries a five-year mortality of 20–45%. Since the pivotal trials including STABLE and INSTEAD XL, the question of TEVAR for complicated dissection requires no discussion and patients progress with medical therapy alone.

The IRAD demonstrated patients who survive a type A dissection and are discharged from hospital have a plateau in mortality, however patients with type B dissection have a mortality of 25% at three years. These patients therefore constitute a group of so-called ‘uncomplicated dissections’; it is this group, where medical therapy alone is clearly failing—as demonstrated yet again in the recent study by Iannuzzi et al.

“I am convinced we should be treating more uncomplicated type B dissection but two questions remain. 1) What is the ideal timing interval for intervention, and 2) Which patients should be treated?

“We have multiple studies quoting risk factors for aortic progression (entry tear, false lumen and overall aortic

Type B aortic dissection carries a five-year mortality of 20–45%. Since the pivotal trials ... the question of TEVAR for complicated dissection requires no discussion and patients progress with medical therapy alone.

Darren Klass

size) as well as risks for significantly higher mortality (more than three antihypertensive medications), however are these the only surrogates for a more complex disease we do not fully understand? Desai et al (Division of Cardiovascular Surgery, Perelman School of Medicine, University of Pennsylvania, USA) demonstrated a significantly lower complication rate if TEVAR occurred two to six weeks post event. If we could demonstrate reliably an extremely low periprocedural complication rate with an agreed method for TEVAR (PETTICOAT or stent grafting to the celiac), is it possible all uncomplicated dissections would be treated with TEVAR? We do not have the answer yet, but I know if I was unfortunate enough to become a patient, regardless of risk factors for progression, I know what treatment I would demand. Retrospective data or not, I know which Kaplan-Meier curve I want to be on, and it is not the medical therapy one.”

However, TEVAR is twice as expensive as medical therapy in the USA. Costs averaged US$58,000 for medical therapy, compared with US$133,000 and US$200,000 for TEVAR and open repair, respectively.

The present study is the first to include cost data when comparing these treatment options in type B aortic dissections, and no prior costeffectiveness analysis has evaluated TEVAR for uncomplicated dissection.

The price tag associated with TEVAR differs dramatically between countries, though, as is expected from vastly differing healthcare systems. Whilst the cost in this US study is not comparable with medical therapy, in a recent Canadian trial, TEVAR cost as little as CA$61,000, less than half of the US expense. Furthermore, a German study of complicated aortic dissection demonstrated TEVAR to be more costeffective than open repair.

Despite the initial increased cost of TEVAR compared with medical therapy, and the post-therapy surveillance costs incurred by both treatment modalities, the study authors postulate that over a longer time period, TEVAR may demonstrate an improved costeffectiveness, “given the 25% to 40% increased risk for aneurysmal degeneration over time” present in medical therapy.

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Drug-eluting stents

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IMPERIAL long-lesion cohort shows good 12-month outcomes with Eluvia Patients in the IMPERIAL long lesion sub-study with long femoropopliteal lesions treated with the Eluvia drug-eluting stent (Boston Scientific) demonstrated an “excellent” primary patency rate at 12 months (87.9%), significant improvement in patient outcomes through one year, and a good safety profile, the investigators report.

THE DATA WERE presented by William Gray from the Lankenau Heart Institute (Wynnewood, Pennsylvania, USA) at Vascular InterVentional Advances (VIVA; 5–8 November, Las Vegas, USA) during a late-breaking clinical trials session. The results of the IMPERIAL randomised controlled trial showed a primary patency at 12 months of 88.5% for Eluvia compared with 79.5% for Zilver PTX (Cook Medical).

The Eluvia stent gained FDA approval in September 2018. The drug-eluting stent (DES) has a biostable fluorinated polymer matrix and is self-expanding, with a diameter of 6–7mm and a length of 40–150mm.

The primary IMPERIAL clinical study was a 2:1 randomised, single-blinded, non-inferiority trial, including 465 patients, which compared the Eluvia

DES (n=309) with the Zilver PTX DES (n=156) in 65 global study centres.

Sub-study details

Gray described the long lesion sub-study, which was a single arm study involving 50 subjects, from the larger IMPERIAL clinical trial. To be included in the substudy, patients had to have a total lesion length of 140–190mm.

Other inclusion criteria and exclusion criteria were as for the main IMPERIAL trial. Inclusion criteria were for patients with Rutherford category of 2, 3 or 4, as well as lesions in the native superficial femoral artery (SFA) and/or proximal popliteal artery (PPA), stenosis of at least 70% by visual angiographic assessment, and a vessel diameter of 4–6mm. Patients with a target lesion/vessel previously treated with DCB (<12 months prior)

or previously stented, prior surgery of the SFA/PPA in the target limb, use of atherectomy, laser or other debulking devices, or dialysis were excluded.

With regard to baseline lesion characteristics, the average lesion length in the sub-study (162.8mm ±34.7) was approximately twice the lesion length of subjects in the primary trial. There was moderate to severe calcification in 70% of patients, and chronic total occlusion was found in a third of patients in the sub-study. The Kaplan-Meier estimate for primary patency at 12 months was 87.9% at 12 months (compared with 88.5% in the primary trial). The safety profile was shown to be consistent with the IMPERIAL randomised controlled trial (RCT). There were no target limb major amputations or stent thromboses; while clinically driven target lesion

revascularisation (CD-TLR) was 6.5% (compared with 4.5% in the RCT). One patient had stent fractures (an incidence of 2.1%).

Gray stated that the Rutherford class improved from baseline to one month and was maintained after 12 months, with 91.5% of patients improving by at least one category without the need for TLR and 87.2% having no or minimal symptoms (a Rutherford category of 0–1) at 12 months. He also described a significant improvement in Walking Impairment Questionnaire from baseline in all components (p<0.0001).

Gray concluded “the results observed in this IMPERIAL long lesion cohort, when combined with IMPERIAL, MAJESTIC, and an independent registry, suggest excellent performance, regardless of lesion complexity.”

New Zilver PTX global data find 76% freedom from TLR at five years Results from an aggregated data analysis of the use of the Zilver PTX drug-eluting peripheral stent (DES; Cook Medical) in challenging patient populations concluded that risk factors such as Rutherford classification, sex, calcification and diabetes did not have a significant impact on the target lesion revascularisation (TLR) rate in patients treated with the Zilver PTX stent.

“I

t is generally thought that sex, calcification and diabetes may have an impact on TLR, but these data demonstrate that these factors do not,” said Mark Breedlove, vice president of Cook Medical’s Vascular division. “In this global analysis of Zilver PTX patients, these characteristics did not have a significant impact on TLR.” The global data analysis on the world’s first drugeluting stent in the superficial femoral artery (SFA) included nearly 2,400 patients from 16 countries who participated in one of five Zilver PTX studies. This included three pre-market studies in North America, Asia and Europe and two post-market studies in the USA and Japan. The study sought to identify the impact of patient and lesion factors on freedom from TLR at one year. The results indicated that factors typically impacting reintervention rates did not have an impact on the reintervention rates for patients treated with the Zilver PTX stent.

In terms of both patient and lesion characteristics, this cohort represented a challenging population to treat.

Half of the patients enrolled in this study were diabetic, the average lesion length was 11.1cm, 36% had total occlusions, 13% had in-stent restenosis, and 14.7% of patients had critical limb ischaemia (Rutherford category 4–6).

Patients treated with the Zilver PTX stent achieved a higher percentage of freedom from TLR compared to standard of care endovascular treatment, resulting in 91% freedom from TLR at one year and 76% at five years.

When questioning what patient and lesion factors impact TLR rates, the study investigators considered a number of factors that could be considered high risk for TLR. The patient factors included sex, smoking status, Rutherford category, the number of patient runoff

vessels, and if the patient was diabetic or not. The lesion factors included lesion length (arbitrarily divided into short and long, with anything over 15cm classified as long), total occlusion, in-stent restenosis, degree of calcification (on a scale of non-moderate to severe), reference vessel diameter, stent diameter, and stent oversizing (using 30% as the discriminator).

Dake et al performed both a classification tree analysis to rank factors in terms of their contribution towards TLR: most impact, moderate impact, or minimal impact. In-stent restenosis, lesion length, reference vessel diameter and total occlusion were all found to have the most impact on TLR, while Rutherford category, sex, degree of calcification and presence of diabetes all had minimal impact.

In a separate analysis, Dake and colleagues used a cox proportional hazards model to confirm the impact of the patient and lesion factors and to evaluate the interactions.

Using this model, the factors that were most impactful on TLR were in-stent restenosis (p<0.001) and total occlusion (p<0.001). In a lesion without restenosis, lesion length becomes the most important contributing factor.

Shorter lesions were found with this model to be more likely to be free from TLR. In vessels without chronic total occlusion, reference vessel diameter “comes into play and is significant in these non-CTO lesions”, as Dake informed the VIVA audience. Stent oversizing had a moderate impact on TLR: stents that were more than 30% oversized had less freedom from TLR than those that were less than 30% oversized.

Both the classification tree analysis and the cox proportional hazards model agreed that Rutherford category, sex, degree of calcification and diabetes had no significant impact on TLR. Commenting on this, panel moderator Dierk Scheinert (University-Hospital, Leipzig,

Michael Dake

Germany) asked: “The finding that calcification is of minimal importance is probably a bit contradictory to our experience. Is that potentially due to the fact that calcified lesions were not so prevalent in the studies in general, or was it more a classification issue?”

Dake responded that it was “probably a classification issue”, saying: “Of all these factors, this is the most subjective. I am not sure if we can ascribe a high level of accuracy to the calcification discrimination between heavy and not—but I think most people know heavy when they see it. Even in a randomised clinical trial with CoreLab adjudication, calcification was not necessarily as important as we might have predicted.”

Scheinert also queried if the results were surprising to Dake, adding: “The significance of in-stent restenosis is expected; we all know that it is a very significant predictor for early recurrences. Total occlusions, I would also say are not a big surprise. It is a bit surprising that lesion lengths and vessel lumen diameter are coming out so strongly.”

Dake concurs: “I think it lends some support and buttresses some of the biases we have held based on realworld data. I think that in terms of the total occlusions, there was some hope that drug-eluting therapies would erase the traditional differences in outcomes between stenotic lesions and complete occlusions—at least in the short lesions. When you get to longer lesions however, you are seeing that the outcomes for long complete obstructions will not be as good as the results for long stenotic lesions or short occlusions.”

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Chimney EVAR rising: Will the technique overcome perceived shortcomings and move to the next level in 2019 and beyond?

Konstantinos P Donas Frank J Criado Comment & Analysis In this article, Konstantinos P Donas and Frank J Criado review the evidence for endovascular aneurysm repair using the chimney technique, and consider where current guidelines and research are leading the vascular community when it comes to endovascular strategies for complex anatomy aneurysms.

HISTORICALLY, THE CHIMNEY technique for endovascular aneurysm repair (ChEVAR) emerged as a rescue technique to revascularise or preserve covered critical branches during aortic endografting. Next in its evolutionary path was the observation that ChEVAR offered a viable treatment option for complex aortic repair involving one or more branches, and particularly so in situations where fenestrated repair was not an option due to anatomical constraints or other fenestrated endovascular aneurysm repair (FEVAR) shortcomings.

In this context, it was appreciated early on that ChEVAR offered two distinct advantages: off-the-shelf availability, and lower resource-intensity that enabled performance by a larger number of operators managing patients in many centres around the world.

ChEVAR adoption grew steadily over the years, but suffered a notorious absence of strong scientific evidence to underpin the technique. This all changed in 2015 with the publication of clinical results in the landmark PERICLES Registry, demonstrating excellent outcomes in a wide range of complex-anatomy aneurysm patients treated by parallel-graft experts at key

medical centres in Europe and the USA. The next evolutionary milestone focused on specific device combinations (aortic stent-graft and chimney stent), how they influenced results, and, more pointedly, the formation of gutters and related endoleaks. The PERICLES Registry collaborators identified two key factors in the causation of persistent gutters. One was the degree of aortic stent-graft oversizing, and the other related to the length of the new seal zone. The investigators suggested treatment by Onyx and Coils embolisation in the sizing cases and by extension and lengthening of the landing zones in case of primary short new neck creation.

Critically important—and often overlooked—is the observation that the majority of ChEVAR gutter endoleaks detected on completion angiography have resolved spontaneously by the time the first postoperative computed tomography angiography (CTA) is performed. Furthermore, it is not unusual to hear during presentations and discussions at various meetings that ChEVAR gutter endoleaks tend to be lumped together as the sum-total of those detected on

ChEVAR gutter endoleaks tend to be lumped together as the sum-total of those detected on completion angiography, first CTA—and even late-onset endoleaks.

Figure 1: Type IA endoleak after endovascular aneurysm repair 12 years ago

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Figure 2: Transfemoral placement of a periscope graft (Viabahn, Gore) in the left renal artery

completion angiography, first CTA—and even lateonset endoleaks. The impact on the inexperienced can be significant, as it may create the misconception or bias against ChEVAR as a largely ineffective and flawed technique.

But on the positive upside, it is encouraging to see that ChEVAR has been included (for the first time) in the latest 2019 Abdominal Aortic Aneurysm Treatment Guidelines from the European Society for Vascular Surgery (ESVS), where the technique is recommended in urgent cases and when fenestrated repair is unfeasible or contraindicated.

Case report

Here is a case example that illustrates powerfully the significant and increasing role of ChEVAR in the management of complex aortic pathologies: An 88-year-old patient presented with a huge type IA/IB endoleak after an endovascular aneurysm repair performed in 2007. The resultant pressure in the aneurysm sac was causing severe abdominal pain. The angulated neck (Figure 1) and acute symptoms precluded treatment with FEVAR, and her advanced age at almost 90 years old, as well as severe comorbidities, excluded the feasibility of open surgical conversion. Consequently, ChEVAR emerged as the only truly viable technical option for creation of a new proximal neck.

To avoid traversing the heavily calcified supraaortic vessels and minimise stroke risk, we elected to use retrograde transfemoral access with implantation of the chimney graft in the periscope configuration (reversed chimney), and extension of the landing zone with placement of an Endurant cuff (Medtronic; Figure 2).

The patient did well and recovered uneventfully.

Worth noting is that the just published ESVS Guidelines assign the same level of evidence (C) to both ChEVAR and FEVAR. In this context, the ongoing multicentre and absolute prospective trial of ChEVAR (ENCHANT) with prearranged endpoints will bring the technique to a higher level (B) of evidence.

In the end, there is little doubt the controversy surrounding ChEVAR will live on in the foreseeable future, at least to some extent. However, we feel confident that dissemination of the ENCHANT study results and, notably, ChEVAR inclusion as an important treatment option in the 2019 AAA Guidelines by the ESVS will go a long way to propel ChEVAR to its next level in the armamentarium of surgeons managing complex aneurysms. In so doing, the rise of ChEVAR will result in an improved perception of the technique in the vascular community regarding its utility and efficacy.

Konstantinos P Donas is a vascular surgeon at St Franziskus Hospital in Münster, Germany.

Frank J Criado is a vascular surgeon at MedStar Union Memorial Hospital in Baltimore, USA.

Figure 3: Super selective angiography of the left renal artery after placement of the periscope graft

Figure 4: Exclusion of the type IA endoleak by additional placement of an Endurant II cuff after placement of the periscope graft at the orifice of the right renal artery

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SPONSORED BY ENDOLOGIX

EVAR leaders recognised for innovation and impact in aortic therapy

Last year saw a growing debate around the durability of endovascular aneurysm repair (EVAR), and while policy and guidelines have been much debated in the vascular field, in many ways the vascular community united behind the value of the treatment that has grown to prominence in recent decades. At the 2018 VEITHsymposium (13–17 November, New York, USA), an Endologix-sponsored symposium honoured four EVAR innovators and triallists, and provided a forum for discussion of the future of EVAR.

Michael DeBakey pioneered open surgical aortic repair for aneurysm patients, introducing the graft technique to the abdominal aorta in the 1950’s.

T

he panel and four recipients of this recognition were Jean-Pierre Becquemin, Jan Blankensteijn, Roger Greenhalgh and Frank Veith.

Other acknowledged pioneers included Ted Dietrich, Roy Greenberg, Frank Lederle, Michael Marin, Juan Parodi and Nikolai Volodos. Moderating the session and leading discussion with the panel was Endologix’ chief medical officer, Matt Thompson. The purpose of the session, Thompson explained, was “to celebrate some of the real pioneers in the treatment of patients with abdominal aortic aneurysm (AAA).”

History and lessons learned

The evolution of aortic technology is long and richly filled with visionary individuals who sought better treatments for their patients, and rigorously investigated new techniques. . In the mid-1900’s, aneurysm repairs were pioneered by, among others, Denton Cooley and Michael DeBakey, who in 1955 repaired a thoracic aneurysm using a graft from a cadaver. For nearly 40 years, this revolutionary idea continued to be implemented in AAA patients—saving countless lives. This open surgical repair approach remains

effective and in use today. However, as became clear in the 20th century, an unmet need persisted in the group of patients too unfit or unable to undergo open surgery.

On 7 September 1990, a 70-year-old man with severe chronic obstructive pulmonary disease and severe back pain caused by a 6cm abdominal aortic aneurysm underwent the first successful endovascular aneurysm repair in the Western world. The case, conceptualised and performed by Juan Parodi, Julio Palmaz and colleagues, became the first widely known endovascular repair of the aorta and was described the following year in the Annals of Vascular Surgery.

In 1992, Frank Veith led the team that performed the first EVAR procedure in the USA, thereby cementing the course for clinical studies and therapeutic advancement that would define the field of endovascular aneurysm repair.

Remembering his early career as a vascular surgeon, Thompson reminisced about Parodi’s first EVAR publication and what it meant to him and his peers: “We had aspirations when endovascular aneurysm repair was introduced, that we could impact the hierarchy of outcomes that we described to our patients; we had

Juan Parodi is widely recognised as the originator of the endovascular aortic stent graft in the Western world. Parodi performed the first EVAR procedure in Argentina together with Julio Palmaz in 1990. He later brought the technique to the USA, where he performed the first EVAR together with Claudio Schonholz, Frank Veith and Michael Marin in New York, 1992.

aspirations towards all-cause mortality, and to reduce aneurysm-related mortality—particularly the perioperative mortality associated with open surgery, and reduce the number of therapy complications, and obviously, make the surgery easier and safer.”

For a more vulnerable patient population, EVAR provided a minimally invasive technique that began to challenge the gold standard of open repair for AAAs. To investigate the comparative merit of EVAR versus open repair, randomised controlled trials were instigated in Europe and the USA: first of these large-scale studies was EVAR 1 in the 1990’s, led by chief investigator Roger Greenhalgh of Imperial College in London, UK. The DREAM trial, with Jan Blankensteijn as principal investigator, was subsequently rolled out in the early 2000’s at centres in the Netherlands. The OVER and ACE trials followed, the former by Frank Lederle and colleagues at centres across the USA; the latter with Jean-Pierre Becquemin as study chair of the trial in Paris, France.

Developing a considerable amount of evidence, these trials paved the way for understanding of the treatment that was revolutionising vascular surgery, and helped to form new paths for innovation in endovascular graft devices. As the evidence amassed across the studies for benefits of EVAR in the short-term, new challenges were identified in long-term outcomes and follow-up protocols. As a result, a new era of vascular device technology development began, leading to the range of endoluminal devices that are currently available to endovascular specialists across the world.

However, large-scale randomised controlled trials have since dwindled, and only long-term outcomes of these early trials remain to compare evidence for open versus endovascular repair. The Endologix symposium in November 2018 therefore sought to inspire triallists to follow in the footsteps of the pioneers in the field, to produce new data using latest generation devices and techniques, and to continue to improve treatment options for all patient populations with abdominal aortic aneurysms.

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Advertorial

SPONSORED BY ENDOLOGIX

Trials and tribulations of EVAR The symposium in honour of the four triallists and innovators served, in part, to highlight the anatomy in vitro and create grafts that achievements and seminal works produced by the panel. Looking back at their careers, these vascular can handle each anatomy securely—I surgeons trace the history of endovascular aneurysm repair treatments through the challenges they think that is the future.” faced in their efforts to introduce EVAR to the field.

Jean-Pierre Becquemin

Frank Veith and Jean-Pierre Becquemin

Frank Veith

“Frank Veith has been a visionary in the field for many years,” Matt Thompson said at the symposium. Working with Juan Parodi and others to perform the first US endovascular repair, as well as the first ruptured aneurysm repair, Veith’s work extends far beyond the VEITHsymposium—one of the largest annual vascular meetings in the USA— which he started and still chairs. “He remains an inspiration to all of us,” Thompson said.

In the early 1990’s, Veith worked in what he described as a “very disadvantaged hospital” in the Bronx area of New York, USA. With a patient population that was poor and very sick, Veith said he was always an endovascular enthusiast, hoping the

Parodi and succeeded in bringing him to their centre in the Bronx to perform with them the first ever US EVAR— despite “tremendous resistance” from the hospital, Veith adds.

When Parodi and Schonholz arrived at Veith and Marin’s operating room, they were reportedly shocked to find the equipment being used, which Veith said was a “primitive” range of machines, including a fluoroscopy imaging machine that had previously been discarded by the hospital’s canine cardiology laboratory. Nevertheless, “the case went magnificently,” and the collaborators set out to create an endovascular stent graft programme.

Veith remembers a significant amount of opposition to the idea in the early stages. In pioneering the technology,

I think all of us here around this table are convinced that EVAR is best for the patient—so now we must convince others. technique could provide his patients with an alternative treatment option.

Having seen Parodi’s concept of the stent graft procedure, Veith became intensely interested and involved with Parodi. When he and his colleague Michael Marin received an aneurysm patient too old and sick to undergo an operation, they started a dialogue with

Veith was warned he was taking risks that were too great, that his championing of these procedures could tarnish the associations he took part in, and that, due to his purported medical recklessness, he might even go to jail. To these warnings, Veith said he knew he was taking risks, “but we thought they were worthwhile.

So we kept persisting.”

On the struggle to drive practice towards EVAR, Veith pointed to the lack of options for the patients that were first provided with this treatment, rather than simply the momentum of the large randomised trials. He explained: “A lot of things drive practice. What drove us was that we had patients we could not treat in any other way. We had patients who were incredibly sick, whereas the clinical trials were performed in relatively easy patients, and that is where the value of the randomised trials came in. I am a great believer in randomised trials, but I am also somewhat critical of some of them, because they can contain design flaws and other flaws—and they are influenced by the bias of the people that conduct them. We, of course, are all influenced by our own biases, and my bias was that endovascular treatment for sick patients was better because they survived it. They died when we did big open operations.”

As president of the Society for Vascular Surgery (SVS), Veith dedicated his presidential address in 1996 to raising awareness of the endovascular technique for aneurysm repair. The message, he said, was lost on many ears, but luckily it reached the younger and open-minded members of the audience, who went on to herald in the new era of vascular surgery.

Imagining the future of vascular surgery is an exciting prospect for Veith, as technology develops to create patientspecific devices. “I think the concept of using computerised techniques to model

The study chair of the ACE trials, Becquemin’s “many contributions to vascular surgery cannot be underestimated”, Thompson stated, adding: “His commitment to education goes through the randomised trials and into all aspects of vascular surgery.”

Becquemin also chairs a European annual meeting, Controversies and Updates in Vascular Surgery (CACVS), which takes place each year in Paris, France. The meeting is co-chaired by Stéphan Haulon.

For Becquemin, reading the first EVAR publication by Parodi as a board member for the Annals of Vascular Surgery was a “revelation”. While some readers of the paper dismissed it, Becquemin pushed for the journal to accept it for publication. In France, even as data started to emerge from the EUROSTAR registry and other studies showing the merits of endovascular repair, surgeons were largely against the new development. The only way to begin to implement the use of endografts, Becquemin said, was to organise a randomised controlled trial.

The ACE trial was a multicentre, prospective randomised trial aimed at assessing the results of EVAR as compared to open repair in “relatively good-risk patients” presenting with an asymptomatic abdominal aortic or aortoiliac aneurysm.

Unfortunately, unlike EVAR 1, the ACE trial never reached long-term outcomes. “We could not get the funding for long-term results,” Becquemin said, “so we had to stop at mid-term.” In fact, the trial experienced several years of delay and struggled with financial difficulties related to stent grafts for the EVAR procedures. The five-year results, which became the final results of the trial, were presented in 2010, showing that EVAR offered no advantages over open surgery in patients who are low risk for the latter procedure and who have a favourable anatomy for EVAR. However, as is echoed in other trials, early impact on mortality/morbidity was better for endovascular procedures—an outcome which many believe is the most important for aneurysm patients, who are often in their 70s and 80s. “It is a tricky thing,” Becquemin said of arguing for government funding of EVAR procedures, “but I think all of us here around this table are convinced that EVAR is best for the patient—so now we must convince others, so that the government can pay for this technology.”

Jan Blankensteijn

The youngest member of the panel being recognised for his contributions,

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Jan Blankensteijn

Blankensteijn was principal investigator of the DREAM trials. Blankensteijn recalls, he was hired by Bert Eikelboom to work in Utrecht, the Netherlands, with the first commercially available endograft. “My very first EVAR case,” he told the audience at VEITHsymposium, “turned out within a couple of weeks to have an anchor— one of the hooks—which had broken.

So at this point [in 1993], all of the initial enthusiasm turned around into a sort of realisation that there might be a dark side to this treatment, that it is not like sewing a graft into the aorta: it is different. So that was where we decided, we need to compare this treatment headto-head with the existing therapy.”

It took Blankensteijn and his team another five years to secure the grant for the DREAM trial, which started around 2000. “By that time,” Blankensteijn said, “there were a lot of people who no longer wanted to include patients in the trial because they were already convinced that it was ethically wrong to withhold endovascular repair for these patients.” In other words, physicians were unwilling to let their patients risk randomisation into the open repair arm of the trial, rather than EVAR. “You do not need proof that a parachute works” was a statement put to Blankensteijn at the time, suggesting the trial to investigate the safety and efficacy of EVAR compared to open repair was unnecessary. However, pointing to the quality of the devices used at the time, Blankensteijn argued a more appropriate description of EVAR in 2000 would be “jumping out of airplanes with umbrellas, not parachutes.”

The DREAM trial showed negative results for EVAR in the long-term,

underlining the argument that thoughtful and considered progress is necessary to evaluate the treatment and the improvements that remain to be produced for device durability and anatomy-specific designs. Moreover, as Blankensteijn observed, randomised controlled trials are a necessary tool to guide development, rather than be dismissed as a superfluous expense.

Roger Greenhalgh

Roger Greenhalgh’s considerable influence in the vascular field is evident, as chief investigator of the UK Small Aneurysm Trial (UKSAT) and the EVAR 1 and EVAR 2 trials, as well as founder of the Charing Cross Symposium, a significant international vascular meeting taking place each year in London, UK. In 2018, Greenhalgh celebrated the 40th year of the Charing Cross Symposium, a meeting which Thompson describes as “the seminal vascular meeting in Europe”. Greenhalgh has now appointed a CX Executive Board for the meeting’s 41st edition, yet he shows no signs of retiring as he spent a great part of the year involved in studies on aneurysmal sac growth, follow-up protocols for EVAR patients, and stroke from thoracic endovascular procedures.

Greenhalgh’s continued dedication to producing new EVAR data may be driven by a need to improve the understanding of EVAR 1 results. The “elephant in the room”, Greenhalgh suggested, was the National Institute for Health and Care Excellence (NICE) draft aortic guidelines, the final version of which have not yet been published at the time of writing. While the draft guidelines reportedly were based upon the data from EVAR 1 long-

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Roger Greenhalgh

term results, causing the committee to advise in favour of open repair in an effort to increase cost efficiency for the UK National Health Service (NHS), these data were criticised—not least by Greenhalgh—as outdated and misunderstood.

“This is one of the most embarrassing findings I have ever experienced,” Greenhalgh said of the EVAR trials.

“I feel very guilty that some data that I

and as the authors put it, “its subsequent erosion” as open repair caught up to EVAR within three years. Survival curves remained converged up to eight years of follow-up.

“At 10 years, the lines of all-cause mortality and aneurysm-related mortality came worryingly close together. We modelled this at 15 years to see which way the curves would go.” In the process of this 15-year outcome analysis,

What in retrospect went wrong, is that the devices were not expected to remain in use for over a decade. am associated with is being interpreted by people in the wrong way.” On what went wrong in the interpretation of the outcomes, Greenhalgh commented, “the average age of the patients in EVAR 1 was 74 years; the devices used were designed by brilliant engineers, who expected the patients to live about 10 years, but actually they lived longer than 10 years. What in retrospect went wrong, is that the devices were not expected to remain in use for over a decade—and they were designed in 1996.” The lack of knowledge at the time in terms of the amount of follow-up that would be required was another limitation in the trial design, Greenhalgh suggested.

In 2017, an Independent Patient Data meta-analysis of EVAR 1, ACE, DREAM, and Frank Lederle’s OVER trial, was published in the British Journal of Surgery. The analysis confirmed the early benefit of EVAR,

Greenhalgh and colleagues found “to our horror” that follow-up was being discontinued. “We know now that it was important to follow EVAR patients.”

Greenhalgh is currently working with colleagues in the UK and Finland on modelling of “what would have happened if we had a perfect follow-up with EVAR 1.” Had patients all been followed, and the trial design had access to current guidelines, Greenhalgh said the data indicate improved long-term outcomes for endovascular repair.

Monitoring, particularly of sac growth, is for this reason an issue which may determine future EVAR guidelines and gold standard follow-up protocols.

Summarising his continued impact in the field, Thompson stated, “Greenhalgh has been an inspiration to all vascular surgeons working in the UK, with his commitment to evidence sustained over many years.”

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Advertorial

SPONSORED BY ENDOLOGIX

Where do we go from here?

Looking back at the history of EVAR makes evident a stark contrast between now and then, as the large-scale randomised controlled trials have increasingly had to give way to single-centre safety and efficacy studies. Endovascular stent grafts are less likely to be tested against each other, unlike drug-coated balloons which have seen recent large-scale trials such as IMPERIAL compare two treatments head-to-head. The physicians honoured in the Endologix-sponsored session at the 2018 VEITHsymposium were chosen for their contributions to clinical evidence, signalling a call to investigators to follow in the footsteps of these previous trials.

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s Greenhalgh described, devices and tools at the start of the EVAR era relied upon more or less crude technology. “Parodi introduced a treatment for the patients who had no alternative, for whom open repair was not an option. There was nothing else we could do for them, apart from EVAR. So we did that. It was not until companies started to produce devices which had quality— not until about 1999—when it became clear that good devices would be available, with some hope of durability, that it was going to be an option for a larger population.”

Whilst short-term perioperative results were clearly in favour of EVAR over open repair, Thompson explained “we are now in a situation where we are looking at the long-term results and they are perhaps a little bit more controversial with regards to durability.”

For Veith however, long-term results are less important than the perioperative benefits of EVAR. “I do not need long-term results,” he stated, “if I were an aneurysm patient, I would want a lower risk of death in the immediate future—I would be less worried about complications eight years from now.

So for me, the outcomes of these trials were terrific. They enabled us to perform this procedure in better-risk patients.”

Like Greenhalgh, Veith suggests that the

From left to right: Frank Veith, Jean-Pierre Becquemin, Jan Blankensteijn, Roger Greenhalgh and Matt Thompson

average age and health of the aneurysm patient population who cannot undergo open surgery should be considered, as they may be likely to opt for a better chance of survival in the immediate few years, albeit with potential reinterventions later on.

To illustrate this problem, Veith pointed to his early EVAR experiences.

“Out of our first 100 patients, we had one or two that survived beyond five years—I think one patient made it past 10 years. For aneurysm patients, the

that, regarding reinterventions after EVAR and the cost of a more rigorous follow-up protocol to measure sac growth and other risk factors, emerging technology may simplify this process significantly. Devices that allow patients to monitor their aneurysm sac and flag any growth to their clinician could provide a cost-saving and safe alternative. Similarly, improvements to device design and imaging technology is cause for excitement on the panel, who hope to see patient-specific devices

How do we produce evidence in the best way going forward? Is it with registries? More randomised trials? National databases? average age is 74, many of them are over 80. It is what happens in the first five years that counts. Then, most of the others die or are in a nursing home. I just think that these conclusions from the NICE draft guidelines have to be fought.

The medical and surgical profession within the UK should rise up against them. The problem is that some of the surgeons are still living in the 1980’s, and are anti-endovascular therapy. That, of course, weakens our case.”

Greenhalgh further pointed out

for complicated anatomy, and advanced imaging to ensure accurate deployment, further reducing risk of reintervention.

So are new large-scale randomised controlled trials needed at this stage, to produce evidence based on treatment with more current devices, and incorporating sac-growth monitoring and rigorous follow-up protocol in order to prevent late rupture deaths? Thompson noted that although “most of us are convinced that endovascular therapy is the way forward,” he questioned the

panel on the way to produce data on EVAR. “We now have a huge range of devices. We have this great wealth of data from the randomised trials and we have good patient selection tools, so how do we refine our evidence going forward? Because we are not seeing new randomised trials. We may be in an era where we simply are not going to see them. We certainly, unlike the cardiologists, do not compare how devices work in comparison, against each other. So how do we produce evidence in the best way going forward?

Is it with registries? More randomised trials? National databases?”

To Thompson’s questions, Blankensteijn argued that while the economics of randomised controlled trials pose an obstacle, they remain important for producing reliable data. “I realise it is becoming increasingly difficult to find the funds to run randomised trials, and it is becoming increasingly difficult to find the differences to randomise to: these differences are getting smaller and smaller.” Blankensteijn highlighted the grey areas that registries and current device trials cannot elucidate on, such as whether to use an infrarenal device or a fenestrated device in a short neck anatomy. Other than conducting a randomised trial, Blankensteijn said “I see no other solution. Registries are not going to solve these issues.”

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Percutaneous bypass safe and effective in long, complex femoropopliteal lesions Initial results of the largest prospective series evaluating the percutaneous treatment of long, complex SFA lesions demonstrate “excellent long term safety” and “promising durability” at 18 months, preliminary results from the DETOUR I study show. Ehrin Armstrong (Rocky Mountain Regional VA Medical Center, Denver, USA) presented these data at the Vascular InterVentional Advances annual conference (VIVA; 5–8 November, 2018) in Las Vegas, USA. ENDOVASCULAR THERAPY IS now generally considered the first choice treatment option for simple, short lesions (often in the realm of 80–120mm), for which there is a wealth of device data demonstrating a high patency rate. However, there is a dearth of data investigating long-segment femoropopliteal disease—hence the ongoing DETOUR I study. In real-world practice, physicians encounter a high percentage of long, complex lesions: with severe calcification, in-stent restenosis, or long segment chronic total occlusions (CTOs). Endovascular performance endpoints from meta-analyses investigating long, complex lesions are often in the range of 59.5% primary patency at 12 months, according to Armstrong, who suggests this describes “a large, unmet

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Late-breaking trials

need for finding an endovascular solution for these more complex lesions, and to obtain a durability more in line with that of surgical bypass.”

As the prospective, single-arm, multicentre DETOUR I trial met both its primary safety and primary efficacy endpoints at 18 months, this is exactly what the DETOUR procedure— percutaneous endovascular bypass— achieves. Of the 81 lesions under study, 96% had CTOs, 68% were severely calcified, and the mean lesion length was 370mm, the longest reported in any study to date (essentially all of the lesions were over 250mm, and more than one third of them were over 40cm).

Armstrong describes the DETOUR procedure as utilising surgical principles whilst using an endovascular approach.

Ehrin Armstrong

From the common femoral artery, the DETOUR device passes through to the femoral vein, and then returns to the popliteal artery, thereby forging an endoluminal stent graft bypass via the femoral vein. This involves using a TORUS stent graft, a specialised DETOUR crossing kit—which allows access via the posterior tibial vein—and a SNARE catheter (both PQ Bypass) to capture the wire, go into the vein, and then puncture back into the popliteal artery.

Results

The DETOUR I study was a clinical evaluation of the DETOUR procedure for percutaneous bypass. A total of 77 patients with 81 limbs were enrolled, and follow-up was initiated at 30 days, and will continue up to 36 months.

Eighteen months after percutaneous

endovascular bypass, primary patency was maintained relative to 12 months, with a primary patency estimate of 67.6%. The primary assisted patency was 78.9%, and the secondary patency was 94.4%.

With regards to safety outcomes through 18 months, Armstrong reports an “excellent freedom from death”, a 74.6% freedom from clinically driven target lesion revascularisation (TLR), 98.8% freedom from acute limb ischaemia, and a 98.6% freedom from major amputation, “consistent with the excellent safety profile of this [DETOUR] device”.

As the device travels through the femoral vein in addition to the common femoral artery, venous health was also assessed at baseline at 18 months. Scoring scales including the venous clinical severity score (VCSS) demonstrated no significant change from baseline.

The study investigators also report “very significant” in functional improvement at 18 months: while the majority of patients were classified as Rutherford Class III at baseline, by 18 months more than 80% of patients enrolled in the study were Rutherford Class 0, and had no significant claudication. The ankle branchial index was maintained through to 18 months.

The DETOUR II investigational device exemption (IDE) trial is currently enrolling at 40 centres across Europe and the USA, and up to 292 patients with long, complex femoropopliteal lesions will be included in this second prospective, single-arm, multicentre study that will include follow-up through to three years.

Preliminary findings from the MIMICS-3 registry find “clear clinical benefit” of BioMimics 3D stent Data from three MIMICS studies support the haemodynamic, biomechanical, and clinical benefits of the BioMimics 3D swirling flow stent design (Veryan Medical). Thomas Zeller (University Heart Center Freiburg, Bad Krozingen, Germany) presented the most recent interim results of the MIMICS-3D registry at the Vascular InterVentional Advances annual conference (VIVA; 5–8 November, 2018, Las Vegas, USA).

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n initial prospective, randomised, controlled trial investigating the BioMimics stent vs. the straight LifeStent (Bard, now BD) at eight German centres demonstrated safety and promising clinical performance at 12 months in the treatment of peripheral arterial disease (PAD) patients undergoing femoropopliteal artery intervention to two years’ followup. Those treated with BioMimics 3D also had better primary stent patency at 24 months (P<0.05).

Next, physicians enrolled 271 patients in the MIMICS-2 trial, a multinational, prospective investigation following IDE approval in the USA, Japan and Europe. This met 30-day safety and 12-month primary patency endpoints, and longer-term outcome data are accruing in the ongoing follow-up through three years.

These most recent results represent interim data from the MIMICS-3D European registry, investigating the nitinol stent in a challenging population of PAD patients.

A total of 505 patients across 23 sites are enrolled in this ongoing study. The primary safety endpoint is a composite of major adverse events or clinicallydriven target lesion revascularisation (CD-TLR) through 30 days, and the primary outcome measure for effectiveness is freedom from CD-TLR through 12 months. An independent clinical events committee adjudicated major adverse events.

Interim data on the first 200 enrolled patients

demonstrated “a clear, clinical benefit”, and the primary safety and efficacy endpoints were met at 12 months.

Technical success of the BioMimics 3D procedure assessed by the operator for the entire enrolled population was 98%. Early results also show a 12-month freedom from TLR of 90%, which closely tracks the values for the MIMICS randomised controlled trial and MIMICS-2 study, despite treatment of more complex disease.

The mean Rutherford category of this subset of the enrolled patient population was reduced: from 2.2 at baseline to 1.2 at 30 days, and 1.1 at 12 months. The percentage of patients with improvement of at least one Rutherford category or more compared to baseline was 88.5% (115/157). In addition to the persistent decrease in Rutherford category over time, the MIMICS-3D study also witnessed a significant improvement in the ankle-brachial index through to one year.

The PAD patients enrolled in the MIMICS-3D study have longer, more complex lesions than in the previous two MIMICS trials; complementary use of a drug-coated balloons occurred in 50% of procedures.

Approximately 25% of the included patient population had critical limb ischaemia, which Zeller noted was an exclusion criterion for previous studies. There was also a significant degree of calcification: grade 3 and 4 calcification on the PACSS scale was found in approximately 20% of the cohort. The longest stent

implanted in the study was 15cm; in about a quarter of the lesions, more than one stent was implanted.

The BioMimics 3D stent is designed “to provide optimal radical support, flexibility, durability, visualisation, and delivery accuracy for femoropopliteal intervention,” according to Veryan Medical. Zeller describes how the unique, 3D helical design of the stent “imitates nature, as arteries are rarely straight.”

He elaborates: “[The BioMimics 3D stent] induces a helical shape to the artery. So it changes a straight vessel segment—this is of particular importance in the SFA [superior femoral artery] segment, which is mostly a straight vessel. By changing the shape of the artery, it changes the shape of the flow pattern inside the stent to a helical laminar flow. This laminar flow resides in a higher pressure applied by the arterial flow towards the vessel wall (the shear stress), and there is a threshold where it is protective against stenosis development.

That is the difference to regular slotted tube stents.

Additionally, the helical design of the stent better absorbs extra compression forces compared to a straight stent.

In all three MIMICS studies, there have been no confirmed stent fractures. These emerging data continue to support the hypothesis that intentionally rendering the stented femoropopliteal artery segment helical (and thus imparting swirling blood flow) improves the outcome of peripheral intervention.

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Critical limb ischaemia

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ADVERTORIAL

CASE REPORT: SFA-CTO Recanalization by using the novel 0.035” UltraScoreTM Focused Force PTA Balloon and DCB Ralf Langhoff, chief, Angiology/Vascular Medicine, Sankt Gertrauden-Krankenhaus, Berlin, Germany, reports on a case in which his team used a novel 0.035” UltraScore™ Focused Force PTA Balloon (Bard, now BD) as an adjunctive therapy with the LUTONIX® drugcoated balloon (DCB) to recanalise a chronic total occlusion (CTO) in the superficial femoral artery (SFA).

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68-year-old female was referred to our vascular center for intermittent claudication primarily in the right leg (Rutherford category 3). She is a current smoker with additional risk factors for atherosclerosis, which are arterial hypertension and dyslipidemia with high cholesterol levels. She had a pain free walking distance below 50 meters, with an Ankle Brachial Index (ABI) of 0.63 on the right side.

After the referring angiologist performed a duplex examination, the test revealed a diseased SFA from the origin of the artery with an occlusion at the distal end. The total length of the diseased segment was 260mm (Fig. 1).

To avoid long segment stenting and to prepare the vessel for better drug-uptake, we intended to intraluminally cross the occlusion and follow with a dedicated scoring balloon for percutaneous transluminal angioplasty (PTA) and vessel preparation.

We used a cross-over access from the left transfemoral with a 6F Fortress Introducer Sheath, 45cm length (Biotronik) and passed the lesion with a 0.035” GLIDEWIRE® , 260cm length (Terumo).

As support, we used a 4F multi-purpose catheter, TEMPO AQUA ® (Cordis, now Cardinal Health).

Subsequently, vessel preparation was performed with the novel Ultra S core™ 5mm x 200mm scoring balloon (Bard/BD), which runs on a 0.035” wire (Fig. 2). The intention of vessel preparation is to minimize the risk of dissections, and maximize luminal gain to prepare the vessel for local drug delivery and/or stents.

The balloon was inflated slowly, which allowed the wires to provide concentrated force on the diseased vessel wall. This focused force dilatation led to a controlled plaque fracture, improved luminal gain. Additionally, the objective was to limit risk of major dissections (SOGA 2018) as severe dissections are related to negative longterm outcomes in femoro-popliteal interventions (FUJIHARA 2017). After seeing a very good and promising result after the use of the Ultra S core™ balloon, we decided to use DCBs to deliver paclitaxel to the entire lesion.

Furthermore, there is the idea that by using scoring elements during vessel preparation the drug-uptake of DCBs can be increased and optimized (CREMERS 2013). We used two 5mm x 150mm LUTONIX ® DCBs (Bard/BD) with a 1cm overlap to avoid a geographical miss. We chose a longer balloon inflation time of three minutes

Figure 8 Posteroanterior view

Figure 1

Figure 1

Figure 2

Figure 2

Figure 3

Figure 4

Angiogram, not ankle brachial index, best for critical limb ischaemia assessment In a strong message delivered at VEITHsymposium (13–17 November, New York, USA), Raghu Kolluri (OhioHealth Heart and Vascular, Columbus, USA) maintained that in the absence of better tissue perfusion imaging, an angiogram is the best option for assessing ulcer healing accurately and caution should be taken when using only ankle brachial index.

KOLLURI NOTED, HOWEVER, that the current guidelines mostly indicate ankle brachial index as the central point in terms of management of critical limb ischaemia (CLI) patients, and showed a case of a patient who was assessed in this manner and treated accordingly, but still presented with an ulcer at followup due to CLI that was not apparent with ankle brachial index assessment. “The point of this is that the clinical examination of the patient and continued close followup is very important and we should not just depend on ankle brachial index,” he explained.

To further this discussion., Kolluri referenced data (Bunte, M, et al Validation of the relationship between ankle brachial and to brachial indices and infragenicular arterial patency in CLI; Vascular Medicine) from Cleveland Clinic (Cleveland, USA) which found that 29% of patients with critical limb ischaemia were noted

to have ankle brachial index scores that were almost normal (between 0.7 and 1.4).

Additionally, data from an analysis of the IN.PACT DEEP trial which looked at 350 critical limb ischaemia patients and the haemodynamic parameters used to

Clinical examination and continued close follow-up is very important, and we should not just depend on ankle brachial index.

because we revealed a short, minor dissection in the former occluded part of the lesion. We decided against provisional stenting because results of the large DCB trials reported strong effects of positive remodeling after application of paclitaxel to the vessel wall via a balloon (TEPE 2013).

Control angiography demonstrated a very good result, with a small minor dissection which was not flow limiting in several projections.

The intervention was finished without any complications and a good outflow (Fig. 3). We used a MYNXGRIP ® device (Cordis/Cardinal Health) for hemostasis and vessel closure.

After the case, the patient was free of any ischemic pain while walking.

Figure 3

Figure 11

References 1. Soga Y, Ando K. Effect of an NSE PTA balloon in experimental lesion models. Cardiovasc Interv Ther. 2018 Jan;33(1):35–39.

2. Fujihara M, et al. Angiographic dissection patterns and patency outcomes after balloon angioplasty for superficial femoral artery disease. J Endovasc Ther. 2017;24:367–75.

3. Cremers B, et al. Inhibition of neo-intimal hyperplasiain porcine coronary arteries utilizing a novel paclitaxel-coated scoring balloon catheter. Catheter Cardiovasc Interv. 2014 Dec 1;84(7):1089–98.

4. Tepe G, et al. High-grade, non-flow limiting dissections do not negatively impact long-term outcome after paclitaxel-coated balloon angioplasty: an additional analysis from the THUNDER study. J Endovasc Ther. 2013;20:792–800.

diagnose it showed that even though these patients had CLI, over 28% had normal ankle brachial index and many had ankle brachial index >1.4. “So ankle brachial index is probably not a good measure to assess critical limb ischaemia,” Kolluri said.

Finally, data from a group in Michigan, USA (Sukul, D, et al, JACC Intervention, 2018) looking at heterogeneity in ankle brachial index prior to revascularisation for CLI in 4,391 patients found that a quarter of CLI patients had normal ankle brachial index. “The other disturbing fact is that when you look at non-compressible ankle brachial index scores, a majority of these patients—especially in the posterior tibial artery—could potentially be upwards of 80% occlusions. So basically, if you get noncompressible vessels, you could be looking at having a potential occlusion in the below-the-knee vessel,” Kolluri explained.

He summarised, reiterating that approximately 30% of patients with CLI will have normal ankle brachial index or non-compressible ankle brachial index, and if they have non-compressible ankle brachial index, upwards of 80% will have potential occlusion or severe stenosis.

“So, at this time, in the absence of better tissue perfusion imaging, angiogram is probably the better way to assess, and we need to consider toe brachial index pulse volume recordings in patients with Rutherford 5 and 6,” Kolluri maintained.

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Interview

Profile

Alberto Muñoz

Alberto Muñoz tells Vascular News about his 35 years in vascular surgery, including his involvement in the World Federation of Vascular Societies, and discusses the landmark advances made in these decades and what he hopes is yet to come.

Why did you choose medicine as a career and how did you decide to become a vascular surgeon?

My father was a born on his family farm near a town called Libano (Tolima), where he grew up. From elementary to high school he was a very dedicated student and he was accepted to medical school at the National University of Colombia in Bogotá, the capital city. He dedicated his life to his patients as a specialist in Internal and Pulmonary Medicine. His main area of interest was tuberculosis (TB) and based on his research he started short-term ambulatory treatment of tuberculosis in our country. This changed the history of TB treatment in Colombia. His approach to patients and medicine influenced me to go to medical school.

At the end of the fourth year, December 1997, I went for a vacation to a small, remote village at the Colombian Pacific Ocean. There was no physician in the village, only a nurse and a small nursery with some sterile instruments, medicines, and sutures. The 1st of January, just after celebrating the new year, I was sleeping and was called because a fight had happened and there where four patients with stab wound injuries in the extremities, that I had to treat. One of the patients had a pulsatile bleeding from his radial artery and the nurse was compressing it when I arrived. This was my first vascular intervention, an arterial ligation. The four patients did well with the apprentice surgeon sutures.

Who have been your career mentors and what did you learn from them?

I studied General Surgery at Javeriana University in a programme with the National Cancer Institute in Bogotá. There I met my first mentor in Vascular Surgery, Professor Jorge Ulloa Dominguez, from whom I learned lymphography, lymphoedema management, vascular tumours, malformations and varicose vein treatment. I also met another of my mentors, Professor Alvaro Caro, who gave me my first job, as an instructor of Surgery at Samaritana University Hospital, a very active trauma centre, once I finished my residency. With him, I learned trauma. I remember treating subclavian, carotid, aortic, retro-hepatic vena cava, extremity vascular trauma, and emergency surgery. There was not a residency programme for Vascular Surgery in Colombia at that time, so I decided to train in Cardiovascular Surgery at Hospital Militar Central in Bogotá. My mentors Gilberto Clavijo and Tulio Parra, taught me great vessel reconstruction and bypass. The service performed cardiac, vascular, thoracic, transplant and vascular surgery. In 1990 I had the privilege of participating at the UCLA Symposium, a full week course with an outstanding review of all vascular surgery. There I met Dr Wesley Moore and many top vascular surgeons who inspired me. Dr Moore, through this course and his book, was one of my mentors.

In 1993, I met Dr Eugene Strandness from the University of Washington in Seattle, who visited us twice in Colombia, helped us to start our vascular laboratory and gave us the strength to start duplex scanning. Dr Herbert Dardik, who also visited us twice and received me at Englewood, mentored me in complex lower extremities revascularisation.

After the endovascular revolution I felt the need to receive training. In 2009, through a very altruistic and charismatic Canadian from Toronto, Bill Blair, I was

introduced to Tom Forbes, Guy de Rose and Kirk Lawlor at the University of Western Ontario in London, receiving the Vicky Blair Fellowship and performing a one-year Clinical Fellowship, where I participated in more than 350 Aortic Surgeries, 60% endovascular. Working with them changed my career. Dr de Rose impressed me for being a very talented surgeon.

How have you seen the field of vascular surgery change and develop in your 35 years as a surgeon?

It is amazing how it has changed since I started my surgical practice, from pulse palpation and angiography to duplex scanning, CTA, MRA, and digital subtraction angiography, and from open surgery to minimally invasive endovascular or hybrid interventions. The two most outstanding advances in vascular surgery during these 35 years have been non-invasive vascular diagnosis and endovascular interventions. Also, evidence-based medicine and the controlled randomised trial in Europe and the USA for carotid artery disease treatment, EVAR trials, BASIL trial and many others.

What is the state of vascular surgery in Latin America as compared to the rest of the world?

Today, vascular surgery is an independent specialty and 16 countries have a Society for Vascular Surgery.

The Latin American Association for Vascular Surgery (ALCVA) is a Federation that includes all these national vascular societies and is a member of the World Federation of Vascular Societies.

Latin-America vascular surgery has been growing parallel to the rest of the world and has a place in the history of vascular surgery. Significant contributions, from Pirovano, a friend of Alexis Carrel, in Argentina performed the reconstruction of iliac and femoral artery aneurysm with a cadaveric homograft in 1910, lumbar sympathectomy (Diez, 1924), closure of patent ductus arteriosus (Goñi Moreno, 1937), correction of aortic coarctation (Albanese 1939), carotid reconstruction (Carrea Molins 1951), venous femorofemoral bypass (Palma Esperon, 1958) to Parodi’s endovascular repair of abdominal aortic aneurysm (1990), have been made by Latin American surgeons. From its early days, vascular surgery in Latin America has been in constant development and evolution. Patients with different vascular pathologies, including trauma, have received treatment with endarterectomy, aneurysm repair, and bypass surgery techniques. The treatment of venous disease and the practice of ultrasonography and endovascular surgery are also currently performed by vascular surgeons.

Education in vascular surgery varies considerably across Latin American countries. Some have a four-year training programme that includes two years of general surgery and two years of vascular surgery. Others have training in general surgery and cardiovascular surgery. And in other countries, a complete training and certification in general surgery and then two years of vascular surgery. The number of physicians dedicated to vascular care has increased rapidly over the past two decades. The development of endovascular surgery in the past 20 years has also created the need for training.

This demand has been met since it is now part of vascular

surgery training. The practice of vascular surgery is similar in Latin America to the rest of the world, but resources for practice may vary in the different countries.

Which areas have room for change and improvement? How can this be achieved?

We need more technology and resources in public hospitals. Also better organisation of the health system in order to centralise patients with vascular disease. It is very important to maintain training in open surgery. Many of the young trained vascular surgeons are better trained in endovascular surgery and need to be good at both to offer each patient the best treatment.

There is a shortage of vascular surgeons in many countries. One solution is to offer an integrated programme (0–5) in more countries, and to ensure that the title of vascular surgeons trained abroad is recognised in order for them to be accepted to practice, since there are countries where general surgery training is required.

You are the President of the World Federation of Vascular Societies­—why is an organisation like this important?

The WFVS was established by the major vascular societies of the world to provide a forum for the international exchange of educational, political, and scientific issues related to the diagnosis, treatment, and prevention of vascular diseases. Its member societies, representing the major geographic regions of the world are: Society for Vascular Surgery (SVS) representing North America, European Society for Vascular Surgery (ESVS) representing Europe, Australian and New Zealand

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Interview with the co-editors and authors of the Global Vascular Guidelines. Also collaborating on different projects of the WFVS, such as the Global Amputation, that we have been working on under the leadership of Professor Martin Björck from Upsala, Sweden.

And just starting the project of writing the Guidelines for the Management of Carotid Body Tumour.

I hope the WFVS will continue to fulfil its mission of integrating vascular surgeons around the world and that the WFVS annual meetings generate more interest. Also, that it continues to develop projects that benefit the world population in the prevention and management of vascular disease.

What new vascular technology are you watching closely and why?

Technology is developing in such a fast way that I would have to mention many for the diagnosis and treatment of aortic, arterial, carotid and venous disease: fusion technology systems that are used even with a C-Arm or a cath-lab and allow endovascular 3D navigation at a low cost. Tomographic ultrasound is of great value for diagnosis and follow-up of different vascular diseases and treatments.

Fenestrated and branched endografts for the treatment of complex aortic aneurysms and dissection of the ascending, arch, descending and thoracoabdominal aorta. New devices for the treatment of central venous obstruction and cryo-preserved human tissue grafts are among many other new technologies that I am watching closely, because they all represent very useful technologies that will benefit the quality of life of many patients and simplify complex treatments.

Society for Vascular Surgery (ANZSVS) representing Australia and New Zealand, Japanese Society for Vascular Surgery (JVS) representing Japan, Vascular Society of Southern Africa (VASSA) representing Southern Africa, Vascular Society of India (VSI) representing India and the Latin American Association for Vascular Surgery and Angiology (ALCVA) representing Latin America.

A Symposium of the World Federation is held annually at the same time and place as the congress of one of the member societies. This is important since the diagnosis and treatment of patients with vascular disease are in constant evolution. New technologies appear and we need to be aware of them and train ourselves in order to take good care of our patients. The idea is that relevant topics of vascular surgery be exchanged between the various World Vascular Societies in order to provide the best possible management in every corner of the world.

What have you achieved in your term as President and what are your hopes for the future of the organisation?

I have represented the WFVS in different meetings like the SVS Boston, ESVS Valencia, VASA Capetown, Charing Cross London, Padova International Congress, Panamerican Rio de Janeiro, Ecuador Society Quito, Argentinian College of Cardiovascular Surgery (CACCV) Buenos Aires and continue the work of my predecessors in organizing the annual meeting of the WFVS, LatinAmerican Association for Vascular Surgery (ALCVA) and Uruguayan Society for Vascular and Endovascular Surgery (SUCIVE) that was held in Montevideo, Uruguay from 5–8 December, with great success. Collaborating

What is the most interesting paper or presentation that you have seen recently?

The new Global Vascular Guidelines for the management of Chronic Limb Threatening Ischemia (CLTI) that will be published at the JVS and EJVS next year. They are the product of a big effort of the SVS, ESVS and WFVS: an international collaboration in which co-editors Micahel Conte (SVS), Phillippe Kolh (ESVS) and Andrew Bradbury (WFVS) and 58 authors from around the world and different disciplines involved in the diagnosis and management of CLTI have written a document on the clinical classification and staging, anatomical staging and evidence-based treatment of an individual patient with CLTI. It also has recommendations to orient future research in CLTI.

You have had the opportunity to train in many countries—how did you benefit from these experiences?

I have received the benefit of learning from many vascular surgeons from different countries and cities the art, science and practice of the speciality. Learning from them what is not written, through observing surgeries, interventions or by comments and explanations kindly received. Also by observing the differences between patients’ psychology, anatomy and pathology that may vary from one country to another.

What are your interests outside of medicine?

Spending time with my family and travelling for vacation in Colombia or around the world. Reading a good book. Playing basketball or watching the NBA. Waterskiing.

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Fact File

Society appointments

2017–2018 President of the World Federation of Vascular Societies and Councillor for Latin America 2014–2017 Secretary General of the World Federation of Vascular Societies and Councillor for Latin America 2012–2014 President of the Latin American Association for Vascular Surgery and Angiology 2002–2004 President of the Colombian Association for Vascular Surgery and Angiology

Professional career (selected)

2016–present Chief of Vascular Surgery at the Hospital Universitario Nacional de Colombia in Bogota, Colombia 2010–present Vascular and Endovascular Surgeon at the Hospital Universitario Fundacion Santafe de Bogota in Bogota, Colombia 1993–present Vascular Surgeon at the Asociación Colombiana de Diabetes in Bogota, Colombia 1992–present Director and Founder of the Clinica Vascular De Bogota in Bogota, Colombia

Teaching appointments

2008–present Associate Professor of Surgery at the Universidad Nacional de Colombia in Bogota, Colombia 2005–2008 Director of the Graduate Program of Vascular Surgery and Angiology at the Universidad El Bosque in Bogota, Colombia

Education

2009–2010 Clinical Fellow at the University of Western Ontario in London, Canada 2005 Degree in Vascular Surgery and Angiology at the Universidad Militar Nueva Granada-Hospital Militar Central in Bogota, Colombia 1988–1990 Degree in Cardiovascular Surgery at the Universidad Militar Nueva GranadaHospital Militar Central in Bogota, Colombia 1981–1984 Specialist degree in General Surgery at the Universidad JaverianaInstituto Nacional de Cancerología, Bogota, Colombia 1974–1980 Medical Doctor and Surgeon at the Colegio Mayor de Nuestra Señora Rosario in Bogota, Colombia

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Multinational survey highlights lack of consensus on physicians’ preferences on vascular access management after kidney transplantation Through a survey that investigated physicians’ preference for management of vascular access after kidney transplantation, Bram M Voorzaat (Leiden University Medical Center, Leiden, the Netherlands) and colleagues, concluded that no clear consensus on management or treatment preference was reached. The results of this online, multinational survey were published in the Journal of Vascular Access.

F

rom the accumulated 585 responses, Voorzaat et al were able to deduce the factors that were associated with a higher preference for arteriovenous fistula ligation; the two most prominent being a reduced left ventricular ejection fraction, and a high arteriovenous fistula flow. Despite this, in terms of arteriovenous fistula management strategies, disagreement among respondents remained considerable.

In their paper, Voorzaat and colleagues acknowledge that while small observational studies suggest that left ventricular mass could improve after arteriovenous fistula ligation in kidney transplantation patients, large observational studies or interventional trials have yet to be performed. They write: “Data on the current practice of vascular access management after kidney transplantation and recommendations in guidelines on this topic are scarce.” In light of this, the authors set out to investigate physicians’ preferences for fistula preservation or ligation in asymptomatic patients after successful kidney transplantation. Additionally, they aimed to identify the factors influencing these preferences.

The survey, that included eight case vignettes of asymptomatic patients with a functioning arteriovenous fistula following kidney transplantation, was sent to members of eight national and international nephrology and vascular surgery societies. In addition to examining the characteristics associated with treatment preferences, respondents were also asked to state their preference as whether to maintain or ligate the arteriovenous fistula.

In terms of the respondents, the majority were surgeons (55%) or nephrologists (38%), with a median of 13 years of clinical experience and 80 vascular access related treatment decisions in the past year. Regarding treatment preference, the authors argue that the disagreement was “considerable”, with less than 70% of respondents preferring either arteriovenous fistula maintenance or ligation in four out of eight cases. In patients with less pronounced risk factors, the variability in preference was even greater. In discussion of these findings, Voorzaat and colleagues postulated that the best treatment for these patients may remain unknown, as no consensus was reached.

A high arteriovenous fistula flow of 2500 mL/min (beta 0.46; 95% confidence interval [CI]: 0.41, 0.51) and a reduced left ventricular ejection fraction of 30% (beta 0.6; 95% CI: 0.55, 0.65) were found to be independently associated with an increased preference to ligate the arteriovenous fistula. Regardless of this, age was not significantly associated with treatment preferences.

Offering a reason for the latter finding, the authors write: “In elderly patients, the major cause for kidney allograft loss is death with functioning allograft, [whereas] if arteriovenous fistula ligation improves long-term cardiovascular outcomes, young patients could benefit more from timely ligation.”

The authors acknowledge certain caveats present in the current study. Voorzaat and colleagues point to the fact that the survey only elicits information on preferences for prophylactic arteriovenous fistula ligation to improve long-term cardiovascular outcomes, but fails to reflect physicians’ preferences for the fistula management to treat current heart failure or local symptoms. Additionally, the authors emphasise that the responses solely reflect physicians’ preference, which may not match or reliably reflect clinical practice.

In light of the significant variability in physician preference, Voorzaat and colleagues concluded that the current evidence is not convincing enough to recommend routine preservation or ligation of arteriovenous fistulae in kidney transplantation recipients. Instead, the authors write: “We hope that this research stimulates the discussion about optimal care for vascular access after kidney transplantation and results in future studies on this underexposed part of vascular access management.”

The authors further theorised that it may be of value to gain a further insight into the protocols for surveillance that are currently being used globally, in order to propose a consensus-based guideline. Moving forward in this field, Voorzaat et al write that they aim to explore patients’ attitudes towards their arteriovenous fistula in an upcoming surgery. Ultimately, however, they aim to perform a randomised clinical trial examining the effect of prophylactic arteriovenous fistula ligation on renal allograft function, cardiac parameters, cardiac and allcause mortality as well as vascular access complications in patients who restart haemodialysis.

Fewer interventions and lower costs for endoAVF patients compared with SAVF patients

New results show that both incident and prevalent patients with an endovascularly created fistula (endoAVF) using the WavelinQ endoAVF system required fewer interventions and had lower costs within the first year compared with matched patients with a surgical haemodialysis arteriovenous fistula (SAVF). The study was carried out by Renée J G Arnold (Icahn School of Medicine at Mount Sinai, New York, USA) and colleagues and has recently been published in the Journal of Vascular Interventional Radiology.

THE AUTHORS FOUND that in matched incident patients, the event rate was 0.74 per patient-year (PY) for endoAVF versus 7.22/PY for SAVF (p<0.0001), with a difference in expenditures of US$16,494. Similarly, they note that in matched prevalent patients the event rate was 0.46/PY for endoAVF vs. 4.10/PY for SAVF (p<0.0001), resulting in a cost difference of US$13,389. Their time-to-event analysis showed that at one year, 70% of endoAVF patients experienced freedom from intervention versus only 18% of SAVF patients for incident patients; these numbers were 62% and 18% for endoAVF and SAVF prevalent patients, respectively (p<0.0001 for both).

The investigators conclude that freedom from intervention was significantly higher in both incident and prevalent endoAVF patients. Compared with the SAVF patients, endoAVF patients had a significantly lower rate of creation procedures after AVF, resulting in a significantly lower AVF maintenance cost in the first year following AVF creation in these patients.

The aims of the study were to compare the rates of interventions and associated healthcare costs, with the use of Medicare payment rates as a proxy for actual hospital cost data, and interventionfree survival in patients with an endoAVF created using the WavelinQ magnetic-guided RF catheter system to propensity score-matched cohorts in both incident and prevalent end-stage kidney disease Continued on page 36

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Fewer interventions and lower costs for endoAVF patients compared with SAVF patients Continued from page 35

patients who had traditional SAVFs (SAVF cohort) in the United States Renal Data System (USRDS).

Arnold and colleagues note that of the 103,420 patients in the USRDS that met the inclusion criteria, 13,265 were incident patients and 90,105 were prevalent patients. The authors describe the inclusion criteria for the SAVF cohort as follows: traditional SAVF creation during 2011–2013 (Current Procedural Terminology [CPT] codes

Renée J G Arnold

36818, 36819, 36820, and 36821); 18 years of age or older on the date of AVF creation; and continuously enrolled in Medicare Parts A and B during the six-month baseline period before the AVF creation date and the six-month follow-up period after the AVF creation date. The endoAVF cohort included all evaluable NEAT participants (n=60).

Demographic and clinical information for the SAVF cohort was obtained from the US Centre for Medicare & Medicaid services end-stage kidney disease SAFs. Baseline information included age, BMI, sex, race/ethnicity, select medical conditions, and having ever received dialysis. The corresponding data for the endoAVF cohort was extracted from the Novel Endovascular Access Trial (NEAT).

Arnold and colleagues describe how data from the USRDS were abstracted to determine the rate of AVF interventions performed in the first year and associated costs (based on Medicare payment rates) for SAVFs created from 2011 to 2013 in the incident and prevalent patient cohorts. Comparative data for endoAVF were obtained from NEAT. The investigators compared event rates, intervention-free survival, and costs between endoAVF and SAVF cohorts after 1:1 propensity

score matching.

The authors mention a previous study,

by Yang et al, which compared AVF interventions to achieve maturation and maintain vascular access and their associated costs in patients with a new endoAVF versus SAVF patients from a 5% random sample from Medicare Standard Analytical Files (SAFs).

Arnold and colleagues suggest their results are possibly “more illuminating” owing to their “more comprehensive”

Medicare claims, so it is possible that procedure or diagnostic codes may have been entered incorrectly. Additionally, the NEAT population is composed of individuals from Canada, Australia and New Zealand, populations which may differ from the US comparison cohort in unmeasured ways that propensity score matching does not address (e.g., process of care issues, such as use of multidisciplinary care). Finally, the USRDS database does not distinguish between

This device, as well as the procedure, is a revolutionary step forward for haemodialysis access creation and care. end-stage kidney disease patient sample, the ability to analyse incident and prevalent cohorts separately with the use of USRDS, inclusion of BMI in the PS matching, and the use of national Medicare payment rates as the basis for determining costs because the payment rates are consistent across the country and for every hospital.

According to the authors, the study has a few limitations. Interventions in the SAVF cohort were identified from

types of SAVFs placed.

In summary, senior author, Dheeraj Rajan, notes, “Our study found that use of the WavelinQ endoAVF system results in fewer interventions postcreation and greatly reduces costs compared to surgically created AVFs. This device, as well as the procedure, is a revolutionary step forward for haemodialysis access creation and care with benefits for all stakeholders but most importantly for the patients.”

ADVERTORIAL

COVERATM Vascular Covered Stent for the treatment of venous anastomotic stenosis in dialysis access Panagiotis M Kitrou, consultant interventional radiologist, and Dimitrios Karnabatidis, professor of Interventional Radiology, both at Patras University Hospital, Patras, Greece, report on a case in which they successfully used a COVERATM Vascular Covered Stent (Bard, now BD) in combination with a high pressure balloon to treat two significant stenoses.

A

62-year-old patient with a brachio-axillary arterio-venous graft (AVG) was referred from his dialysis center with signs of inadequate dialysis.

The patient’s venogram revealed a significant stenosis at the graft-vein anastomosis and a second stenosis just distal with presence of extensive venous-tributary network (Figure 1).

A 7mm diameter, 80mm length DORADO® High Pressure Balloon (BDPI, Tempe, Arizona, USA) was used to “beat” the stenosis. A flared 8mm diameter 80mm length COVERA™ Vascular Covered Stent was placed to cover both lesions. The final result is shown in Figure 2.

More than 50% of stenosis in AV Access Grafts present within 1cm around the venous anastomosis.1 Therefore, most new technologies have been tested and evaluated in this specific AV Graft segment. A study of paramount importance, published by Haskal et al in 2010, demonstrated a significant patency improvement over plain balloon angioplasty in both Access Circuit and Target Lesion when the FLAIR® Endovascular Stent Graft was used.2 Since then, several studies supported the above mentioned results showing consistency of data.3, 4 Until today, stent grafts are the only devices to provide significant patency improvement at six months compared to plain balloon angioplasty in multicentre randomized controlled trials.

The COVERA™ Vascular Covered Stent is used in our department for the treatment of venous-graft anastomotic stenosis. With our experience of more than 100 devices, the COVERA™ Covered Stent has proven to be an excellent

Figure 1: Stenosis (white arrow) at the anastomosis of a graft (black arrowhead) with a vein (white arrowhead) and a second stenosis (black arrow). Venous tributaries are filled with backflowing contrast medium (white stars). The wire in place can help separating the AVG from the venous tributaries.

and durable solution for the treatment of those resistant and frequently re-occurring lesions. Additionally, the ease of the deploying mechanism is an advantage because it can be controlled by fellows that have limited interventional experience. Data from the AVeVA study (prospective, multicentre, non-randomised, single-arm clinical study) showed a freedom from primary safety events rate of 96.4% and a six-month target lesion primary patency rate of 70.3% for the COVERA™ Covered Stent.

Our algorithmic approach suggests using a Covered Stent at the venous-anastomotic stenosis as a primary treatment in grafts older than 18 months and for patients with symptoms recurring within a short period of time (<3 months) after balloon angioplasty.

Figure 2: COVERATM Vascular Covered Stent deployment at the site of stenosis (white arrow). The synthetic graft can now clearly be seen (black arrowhead) due to complete absence of venous tributaries.

References 1. Kanterman RY, Vesely TM, Pilgram TK, Guy BW, Windus DW, Picus D. Dialysis access grafts: anatomic location of venous stenosis and results of angioplasty. Radiology. 1995;195(1):135-9.

2. Haskal ZJ, Trerotola S, Dolmatch B, Schuman E, Altman S, Mietling S, et al. Stent graft versus balloon angioplasty for failing dialysis-access grafts. The New England journal of medicine. 2010;362(6):494-503.

3. Haskal ZJ, Saad TF, Hoggard JG, Cooper RI, Lipkowitz GS, Gerges A, et al.

Prospective, Randomized, Concurrently-Controlled Study of a Stent Graft versus Balloon Angioplasty for Treatment of Arteriovenous Access Graft Stenosis: 2-Year Results of the RENOVA Study. Journal of vascular and interventional radiology: JVIR. 2016;27(8):1105-14 e3.

4. Karnabatidis D, Kitrou P, Spiliopoulos S, Katsanos K, Diamantopoulos A, Christeas N, et al. Stent-grafts versus angioplasty and/or bare metal stents for failing arteriovenous grafts: a cross-over longitudinal study. Journal of nephrology. 2013;26(2):389-95.

The opinions and clinical experiences presented herein are for informational purposes only. The results from this case study may not be predictive for all patients. Individual results may vary depending on a variety of patient specific attributes. The physician has been compensated by BD for the time and effort in preparing the above case study for BD’s further use and distribution.

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Lutonix Global SFA Real-World Registry. Primary Patency of the target lesion is by investigator assessment based on presenting symptoms and clinical exam and by absence of CEC adjudicated TLR event. Total of 614 subjects were evaluable for primary patency at 12 months. The primary patency success rate at 12 months as determined by subject counts was 83.1%. The primary patency rate for all subjects as measured by Kaplan-Meier estimates resulted in 85.4% for 12 months. ** PK1400100 Rev. 2 04/18 † Virmani et al. Comparison of Particulate Embolization after Femoral Artery Treatment with In.Pact Admiral versus Lutonix 035 Paclitaxel-Coated Balloons in Healthy Swine. J Vasc Interv Radiol. 2016 Nov;27(11):1676-1685.e2. doi: 10.1016/j.jvir.2016.06.036. *

Preclinical data is not indicative of clinical results.

Please consult product labels and instructions for indications, contraindications, hazards, warnings, and precautions. © 2018 BD. BD, BD Logo, Bard and Lutonix are trademarks of Becton, Dickinson and Company. All Rights Reserved. All other trademarks are properties of their respective owners. Bard Ltd. | Forest House, Brighton Road | Crawley, West Sussex, RH11 98P, United Kingdom BPV/LTNX/1218/0296b(1)

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Percutaneous endovascular dialysis fistulae: Here today and gone tomorrow or here to stay?

Robert G Jones Comment & Analysis The first surgically created autologous arteriovenous fistula was described in 1966. Over the past five decades there is no doubt that marked surgical progress has been made in this field but fistulae are still beleaguered with significant failure rates and the need for repeat interventions to maintain patency and functionality.

The surgical creation of a fistula involves manipulation, clamping, dissection and suturing of the vein, which in part contributes to intimal hyperplasia, stenosis and fistula failure. An example of a common site for stenosis is the juxta-anastomotic segment, where lesions develop in approximately 50% of new fistulae at four to six weeks follow-up. This area of the vein is surgically dissected and maximally mobilised from surrounding tissues.

I

n recent years, two different device systems have been developed that are licensed for the percutaneous endovascular creation of dialysis fistulae (EndoAVF) in the proximal forearm without the need for surgical incision or suturing, and early results from clinical trials demonstrate high rates of creation success, patency and usability with low rates of reintervention. Both systems utilise the proximal forearm venous perforator, which is the conduit between the deep and superficial venous system and is thought to be present in up to 90% of the population. Fistula creation using the perforator is not a new concept and in the 1970â&#x20AC;&#x2122;s Gracz and Toledo-Pereyra described surgical fistulae using this vein and the adjacent brachial and radial arteries respectively.

The Technology

The WavelinQ device (BD Medical), (formerly EverlinQ, TVA) is a dual magnetic fluoroscopic-guided catheter system consisting of a venous and arterial catheter and radiofrequency (RF) energy to create a contained AV fistula between the deep arteries and veins in the proximal forearm, typically the ulnar vessels but the radial vessels can be used as well. The superficial veins are then arterialised via the perforator for maturation, and ultimately used for dialysis access. The catheter system is introduced via the brachial or wrist vessels, with the latter being more commonly utilised with the newer 4F version. Initially only a 6F system was available and was too large for wrist access.

The Ellipsys device (Avenu Medical) is a 6F single catheter system, which

Future success and acceptance of endoAVF will be reliant on many factors creates a fistula under ultrasound guidance via a single venous access point in the cubital fossa. The device creates an anastomosis between the perforator vein and adjacent proximal radial artery directly. The superficial venous system of the upper arm is then arterialised via the perforator.

Evidence

Following successful pilot studies, the NEAT (n=60) and PIVOTAL (n=107) trials reported on WavelinQ and Ellipsys individually, with procedural technical success of 98% and 95%, respectively.

Twelve-month patency was 84% for WavelinQ and 87% for Ellipsys, with time to two-needle cannulation of 112 and 114 days, respectively.

Secondary procedures to maintain patency were encountered with both devices. Angioplasty was required in 72% of cases with the Ellipsys device, and 3% with the WavelinQ. However, more recently, angioplasty of the AV anastomosis is being carried out during the primary Ellipsys procedure and has considerably reduced the need for secondary angioplasty.

When an endoAVF is created, the

deep veins are also arterialised. This may require coiling of the brachial vein proximal to the AVF to facilitate diversion of blood through the perforator into the superficial system. Generally, only a single vein is coiled and concerns regarding compromise of the deep venous drainage have not been substantiated.

The devices have demonstrated good safety profiles with serious adverse events reported in only two patients (both haematomas) with the Ellipsys device. The NEAT trial (WavelinQ) reported a 12% complication rate but the majority were related to the brachial artery access site. This is reduced with the 4F system and the ability to carry out the vast majority of these procedures using the wrist arteries, making the procedure safer and more streamlined.

Patient selection and the AV access paradigm

This is relatively straightforward and carried out with Doppler ultrasound, much the same as with surgical screening, with similar vessel size criteria being applicable. In essence, any surgical fistula candidate is potentially suitable for an endoAVF provided they have the perforator and adequately sized veins.

EndoAVF have been successfully created both in patients dialysing via a catheter and in the end stage renal disease (ESRD) pre-dialysis population who meet the criteria for pre-emptive access creation. In patients with failed surgical fistulae, endoAVF are a possibility, as the proximal forearm region is surgically unscathed. In the event of a failed endoAVF, subsequent surgical fistula creation is also possible and outflow veins may be dilated.

There is much debate as to where endoAVF will fit in the access paradigm.

Current guidelines recommend distal forearm fistulae first, but this may not be possible in those with small vessels at the wrist, and here endoAVF as an initial option would be the next logical step.

This would preserve above elbow vessels whilst promoting distal first guidelines.

This is equally relevant and important in those with failed forearm fistulae.

Pushing the boat out even further, basilic and brachial vein transposition is another potential application in the endoAVF space. Whilst all of these options will be a focus of future experience, it is unlikely that endoAVF will be a complete replacement for surgery.

Benefits of endoAVF

Potential benefits are not only the apparent improved patency rates and fewer reinterventions, but also relate to

lack of the disfigurement and scarring associated with surgical fistulae.

EndoAVF do not tend to develop into unsightly aneurysmal vessels and this is in part due to the shared flow these fistulae typically exhibit, with drainage often in a â&#x20AC;&#x2DC;dual dominanceâ&#x20AC;&#x2122; pattern shared between the cephalic and basilic veins in varying degrees.

This is beneficial in that it is attractive to patients as well as increasing the cannulation zone, potentially leading to less cannulation site-related morbidity.

Both techniques of endoAVF creation can be carried out as day case procedures and this will open up the field of specialists able to create fistulae, which gives the potential to decrease wait times for surgical fistula.

Future success and acceptance of endoAVF will be reliant on a number of factors, including securement as a stakeholder in the AV access paradigm, patient choice, continued successful real-world application and acceptable cost and coding. In the USA, both devices recently received a unique reimbursement code. To date, all UK experience has been via the ongoing EU EverlinQ trial but future more widespread use will require appropriate coding and recognition both locally and nationally. This will likely focus on the offset of higher upfront equipment costs balanced against high patency rates, less morbidity and lower rates of reintervention.

Whilst still in its infancy, the technology to create an endoAVF is arguably the most innovative step forward in AV access in decades.

However, as with many innovative devices, it remains to be seen if the promising preliminary trial results will be maintained when widespread clinical usage occurs, and whether the expense of the technology will be accepted over the traditional surgical fistula.

Robert G Jones is a consultant interventional radiologist at University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK References: 1. Rajan DK, Ebner A, Desai SB et al. Percutaneous Creation of an Arteriovenous Fistula for Hemodialysis Access. J Vasc Interv Radiol 2015;26:484-490 2. Hull JE, Elizondo-Riojas G, Bishop W et al. Thermal resistance Anastomosis Device for the Percutaneous Creation of Arteriovenous Fistulae for Hemodialysis. J Vasc Interv Radiol 2017;28:380-387 3. Lok CE, Rajan DK, Clement J et al. Endovascular Proximal Forearm Arteriovenous Fistula for Hemodialysis Access: Results of the Prospective, Multicentre Novel Endovascular Access Trial (NEAT).

Am J Kid Diseas. 2017;70(4):486-497 4. Hull JE, Jennings WC, Cooper RI et al. The Pivotal Multicentre Trial of Ultrasound-Guided Percutaneous Arteriovenous Fistula Creation for Hemodialysis Access. J Vasc Interv Radiol. 2018;29:149-58 5. Jones RG, Morgan RA. A Review of the Current Status of Percutaneous Endovascular Arteriovenous Fistula Creation for Haemodialysis Access. Cardiovasc Intervent Radiol. Published online July 20th 2018.

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Maintenance of arteriovenous accesses may decrease renal graft perfusion Results of a pilot study suggest that the closure of arteriovenous accesses may lead to better renal graft perfusion. The study was carried out by Ivo Laranjinha (Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal) and colleagues, and has recently been published in the Journal of Vascular Access.

THE RESULTS SHOWED that temporary occlusion of an arteriovenous (AV) access causes a “significant decline” in renal graft resistive index and this decline is higher with the occlusion of accesses with higher blood flow rate (Qa). These results suggest that the maintenance of arteriovenous accesses, mainly those with higher Qa, can decrease renal graft perfusion.

The investigators found that after arteriovenous access occlusion 82.4% (n=14) of the patients had a decrease in resistive index. All patients had a decrease in heart rate (67 vs. 58bpm, p<0.001) and 14 (82.4%) had an increase in mean blood pressure (98.3 vs. 101.7mmHg, p=0.044).

There was a significant decrease in the resistive index after the access occlusion (0.68 vs. 0.64, p=0.030). They found a negative correlation in Qa (r^2=0.55, p=0.022) with the decrease in resistive index, and Qa was an independent predictor of the decrease in resistive index in a model adjusted to pre-occlusion resistive index.

Laranjinha and colleagues remark that after a kidney transplant, it is unknown whether the maintenance of a functioning haemodialysis arteriovenous access could have deleterious effects on renal grafts. They hypothesise that maintaining

a functioning AV access after kidney transplant can reduce renal allograft perfusion in two ways. First, deviating a significant proportion of the cardiac output from the systemic circulation, and consequently from the renal graft artery, causing a “graft steal syndrome-like”.

Second, the functional and structural cardiac adaptations secondary to AV access can exacerbate changes in systemic circulation caused by AV access, leading to “cardio-renal graft syndrome-like”.

They aimed to investigate whether temporary closure of arteriovenous access could lead to an increase in graft perfusion.

The authors note that the inclusion criteria were patients older than 18 years who received a single kidney at least nine months before and had a stable allograft function. All patients with signs or symptoms of congestive heart failure, heart arrhythmia, biopsy-proven acute rejection episodes or chronic graft dysfunction, renal artery stenosis, hydronephrosis, perirenal fluid collection, or other anatomic abnormalities of the graft present in any radiologic examination available in the patient records or discovered during the study were excluded.

The investigators enrolled 17 patients

Ivo Laranjinha

in the pilot study. All randomly selected, nine of them were male (53%), with a median age of 56 years, and two (11.8%) were diabetics. From the 17 patients, 16 (94.1%) had an arteriovenous fistula and 10 (58.8%) had an access in a proximal position.

The investigators used the resistive index (RI) measured by Doppler ultrasound as a dynamic marker for the intrarenal vasculature adaptations during the access compression. They note how this has been used as a tool for studying renal microcirculation and is widely used in kidney transplant patients. It is also a non-invasive procedure and has a low cost. Three measurements were performed and the mean value was used

Adductor loop arteriovenous graft found to be a “reliable, safe, and long-term alternative” to autogenous venous access New results indicate that adductor loop arteriovenous grafts can be a reliable, safe and long-term alternative in those for whom fistula formation is not possible and may have a role earlier in the patient journey than previously thought, due to good patency results and fewer complications. The study was carried out over 11 years by Samantha J McEwan (Queen Alexandra Hospital, Portsmouth, UK) and colleagues. The long-term follow-up, complications and patency rates were published in the Journal of Vascular Access.

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he authors describe the adductor loop technique as involving an anastomosis between the femoral vein in the mid-thigh and the superficial femoral artery with subcutaneous tunnelling. The mid-thigh approach was chosen over a more proximal (and traditional) groin approach for several reasons. Notably, it starts as distally as possible on the limb, allowing for insertion of an AVG more proximally if necessary, and does not cross a joint line so, once healed, is less uncomfortable for the patient.

The investigators found that death-only censored primary patency at one, three and five years was 76%, 44% and 23% respectively. Secondary patency at one, three and five years was 95%, 63% and 45%. The authors note that these rates are higher than previous studies looking at lower limb arteriovenous grafts. Graft thrombosis occurred in 14 patients (28%) and six were treated for an infection (12%) but only four grafts were excised, which the authors note is much lower than in previous studies.

McEwan and colleagues remark that infection rates of just 12% may have resulted from placing the arteriovenous graft away from the groin. Parekh et al, among others, suggest this positioning carries a reduced risk of infection. All the mid-thigh adductor loop grafts presented in this study were anastomosed with the femoral vein and superficial femoral artery in the mid-thigh region, therefore avoiding the groin area completely.

The authors note how graft thrombosis was the most common complication in this cohort of patients and is similarly reflected in the published literature. A total of 28% of the cohort thrombosed their AVG at some point in the graft’s history, while six (12%) had multiple thrombotic episodes. Their data are lower than previous published studies that report both higher thrombotic and intervention rates of 36%–54%.

Between January 2006 and March 2017, 50 mid-thigh loop arteriovenous grafts were inserted into 48 patients (32 right, 18 left) and these were all followed up until

in the statistical analysis.

According to the authors, the management of arteriovenous accesses in patients who underwent successful kidney transplantation is a topic of “ongoing debate”. Although AV accesses associated with the best outcomes in dialysis patients are still the access of choice for the majority of patients, there are “growing concerns” about their potential long-term systemic toxicity.

Laranjinha and colleagues recognise that there are few studies evaluating the impact of maintaining AV access on graft function, and these are mostly retrospective and have conflicting results.

They note specifically how Weekers et al describe a faster allograft glomerular filtration rate (GFR) decline after arteriovenous fistula closure, while Vajdic et al found better graft function and better graft survival, one and five years after transplantation, respectively, in patients whose arteriovenous fistulae were closed after transplantation.

Speaking to Vascular News, Laranjinha adds that he and his colleagues concluded, “prospective studies are needed to investigate the long-term consequences of AV accesses occlusion in renal graft function/survival and which patients will benefit more from fistula occlusion”.

December 2017. Twenty-seven of the patients were men, and the median age was 52 years, with a range of 25–84 years. Two patients received a second loop; one in the contralateral leg following thrombosis of the first graft with unsuccessful salvage at approximately 16 months, and one ipsilaterally following presumed infection at just less than 18 months.

A prospective database was collected on patients receiving an arteriovenous graft at the unit by the senior author. All patients remained under the care of the unit ensuring accurate follow-up data collection and the database was updated at regular intervals.

McEwan and colleagues note that due to an expanding and ageing population, definitive access in patients requiring renal replacement therapy is an “everincreasing challenge”. In 2010, the authors published data on mid-thigh adductor loop arteriovenous grafts (AVGs), which provide an alternative route of access.

The paper described 12-month primary and secondary patency rates of 70% and 90%.

According to the authors, autogenous venous access remains the perceived “gold standard” for patients requiring dialysis for end stage renal failure. However, they believe it is time to question the traditional access pathways and offer patients lower limb access procedures with high patency and lower complication rates much earlier in their dialysis journeys.

The study has demonstrated improved long-term primary and secondary patency rates in mid-thigh arteriovenous grafts compared with other published studies with lower limb grafts, as well as lower infection rates. They suggest that mid-thigh adductor loop PTFE grafts provide a “very good” alternative long-term route of access in those patients with end-stage renal failure requiring permanent access for dialysis.

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Retrospective study finds 97% success rate with Surfacer Inside-Out access catheter The Surfacer Inside-Out Access Catheter System (Bluegrass Vascular) has demonstrated positive commercial use, consistently achieving central venous access in patients with upper body occlusions. A study presented in a poster session at the 2018 American Society of Nephrology (ASN) Annual Meeting (23–28 October, San Diego, USA) builds on positive results from the company’s post-market international SAVE Registry announced earlier this month.

THE RESULTS OF the retrospective, independent study evaluating 32 cases with the Surfacer System demonstrated an impressive 97% success rate in all patients. In one patient access was not achieved due to significant scoliosis altering the anatomy. There were zero device-related complications reported, including bleeding, haematoma and catheter-related infection, and all patients displayed similar catheter function at three months.

“The clinical application of the Surfacer System, as

shown in this study, proves to be extremely positive,” states Roman Reindel-Schwaighofer, Nephrology and Dialysis Fellow at the Medical University of Vienna in Austria and the lead author of the study. “The Surfacer System provides a safe and effective solution that both preserves and restores vascular access for patients requiring haemodialysis who otherwise have very limited options.”

The Surfacer System is a CE-marked device designed to reliably, safely and repeatedly gain

central venous access for haemodialysis patients awaiting maturation of permanent vascular access.

Failed venous access attempts may prevent permanent arteriovenous access, increasing patient morbidity and the overall cost of care.

“Based on these results, I am very optimistic about the clinical impact of the Surfacer System and its ability to treat upper body vascular occlusions,” states Gürkan Sengölge, associate professor of Medicine, Nephrology and Intensive Care Medicine at the Medical University of Vienna and the study’s senior author. “The ability to safely perform the procedure, in an outpatient setting, and have the option to repeat when necessary, has the potential to change the standard of care going forward.”

“This is an exciting study that mirrors the commercial successes recently revealed in our international post-market SAVE Registry and similar positive trends observed in our SAVE-US IDE study,” states Gabriele Niederauer, CEO and president of Bluegrass Vascular. “I look forward to announcing additional data as it becomes available and as we near completion of our SAVE-US IDE trial.”

IN.PACT Admiral drug-coated balloon found to be superior to percutaneous transluminal angioplasty for treating femoropopliteal disease at five years Five-year results from the IN.PACT SFA randomised trial were presented by John Laird Jr from Adventist Heart and Vascular Institute (St Helena, USA) at the Vascular InterVentional Advances (VIVA; 5–8 November, Las Vegas, USA). Laird stated that the study showed long-term safety of the IN.PACT Admiral drug-coated balloon (DCB), with no device-, procedure- or paclitaxel-related deaths and low thrombosis rates found in patients during the five years.

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his is the first independently adjudicated, blinded, randomised trial to demonstrate superior effectiveness of a DCB over percutaneous transluminal angioplasty (PTA) over a period of five years, Laird explained.

While numerous randomised trials with DCBs have previously shown improved outcomes of DCBs over PTA, including randomised trials evaluating the three commercially available DCBs in the USA, Laird described the need for “more long-term data from randomised trials for DCBs because there remains some uncertainty over the long-term durability of DCB angioplasty”.

The one, two and three-year results of the IN.PACT SFA Trial have previously demonstrated superiority of the IN.PACT Admiral DCB over PTA, outlined Laird.

Laird described the details of the IN.PACT SFA Trial, which was a prospective, multicentre, multinational, randomised, single-blinded trial that took part in two phases, with 331 patients enrolled and randomised 2:1 to either the IN.PACT DCB (n=220) or PTA (n=111). The results were independently assessed and monitored, with 100% source data verification, and subjects were followed up for five years, he continued.

In phase 1, 150 subjects were enrolled at 13 EU sites between September 2010 and April 2011, and in phase 2, 181 subjects were enrolled at 44 US sites from April 2012 to January 2013.

Laird reported that there was over 90%

compliance with regards to five-year follow-up.

Laird described the primary efficacy endpoint of the trial as primary patency within 12 months, defined as freedom from clinically-driven target lesion revascularisation (CD-TLR) and Duplex ultrasound (DUS)-derived restenosis (peak systolic velocity ratio (PSVR) ≤2.4).

The primary safety endpoint, he continued, was freedom from deviceand procedure-related death through 30 days, and freedom from target limb major amputation and clinically-driven target vessel revascularisation (CDTVR) within 12 months.

Laird described how five-year follow-up assessment was conducted by telephone interview, with all events then subsequently adjudicated by an independent clinical events committee.

The independent committee was blinded to the assigned treatment based on any reintervention at the target lesion due to symptoms or drop of ankle brachial index (ABI) of ≥20% or >0.15 when compared with post-procedure baseline ABI. Laird outlined how major adverse events (including all individual components of the primary endpoints and key secondary endpoints) were adjudicated by the blinded clinical events committee for five years; with restenosis assessed by the blinded Duplex and Angiographic Core Labs through three-year follow-up visits.

When looking at baseline characteristics, Laird described how the

two groups were well matched “with only 5% of patients in the trial having ischaemic rest pain”. While calcification was present in the majority of patients’ lesions, Laird stated that “severe calcification was present in only a small percentage of patients as this was an exclusionary criterion in the trial”.

Results

A durable treatment effect with regards to freedom from CD-TLR was found through five years with a rate of 74.5% for IN.PACT DCB compared with 65.3% for PTA, with a delta benefit of 9.2%, reported Laird.

Any TLR was reduced from 37.5% after PTA down to 26.6% after IN.PACT DCB, although Laird stated that this was not statistically significant. However, he reported “a statistically significant increase in the time to CD-TLR at 807.5 days after DCB compared with 474.9 days following PTA”.

The primary safety composite was seen in 70.7% of cases following DCB compared with 59.6% following PTA, which was, explained Laird “driven by an increased need for TVR”.

Laird described how the difference in all-cause deaths was not statistically significant between the two groups at four or five years; there were no deviceor procedure-related deaths, and only one major target limb amputation in the study; and there was a very low rate of vessel thrombosis, with no new thrombotic events occurring between three and five years. “A careful analysis of all deaths in the trial concluded that

John Laird

no deaths were related to the device, procedure or paclitaxel,” stated Laird.

With regard to durability of treatment, Laird reported “a primary patency of 69.5% following DCB compared with 45.1% after PTA at three years, with a delta benefit of 24.4%”, and “a durable treatment effect regarding CD-TLR, with a delta benefit with regard to CDTLR of 10.1% at five years”.

Laird concluded that “the IN.PACT SFA Trial demonstrates durable effectiveness of the IN.PACT Admiral DCB” and “the results support DCB as a first line strategy for the treatment of femoropopliteal disease”.

Panellist Matthew Menard, from Brigham and Women’s Hospital (Boston, USA), summed up the findings “with five-year data we are now seeing true durability. While we have to decide whether this is representative of the patients we see, it is compelling data.”

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Advertorial

SPONSORED BY LOMBARD MEDICAL

Behind the MiCroPort acquisition of Lombard Medical: What is next?

In April 2018, Chinese medical device company MicroPort Scientific acquired UK-based Lombard Medical, a developer, manufacturer and marketer of endovascular aortic aneurysm repair devices. The two companies had previously collaborated in a strategic partnership. Vascular News speaks to MicroPort’s chief international business officer, Jonathan Chen, about the development and future of the company.

It has been around seven months since MicroPort announced its acquisition of Lombard Medical; what were the reasons and motivation behind MicroPort making this move?

Historically, MicroPort has had a very strong performing endovascular business for our home market in China, where we are a market leader. The endovascular business is one of the fastest growing businesses within MicroPort, growing at over 30% per annum. We considered the Lombard product portfolio to be very attractive, and a good fit from a technological as well as geographical perspective. In terms of technology, we see Aorfix and Altura as two very novel and differentiated stent grafts, that will help us build one of the most comprehensive endovascular aneurysm repair (EVAR) product portfolios in the industry. As for the geography, Lombard is selling in markets (Europe and Japan) that are very complementary with MicroPort’s core endovascular markets.

How has the transition been, moving from the companies’ strategic partnership, to becoming one company?

MicroPort and Lombard have been working together for the prior two years through a strategic partnership that was entered into in December 2016. Through this strategic partnership, MicroPort has helped Lombard

to significantly reduce the manufacturing cost for its stent grafts by leveraging MicroPort’s endovascular manufacturing expertise. These cost reduction initiatives have continued since the restructuring of Lombard. We expect that the improved manufacturing costs will significantly accelerate Lombard’s ability to become a profitable EVAR business.

How do you feel the restructuring has benefitted MicroPort so far?

We see the restructuring as benefitting both Lombard and MicroPort. Firstly, Lombard has gained a very strong strategic partner to develop its EVAR business with manufacturing expertise that has allowed Lombard to demonstrably reduce manufacturing costs and has gained the most capable commercial partner to open the China market for its products, alongside other markets including Latin America. Secondly, MicroPort has gained two very innovative abdominal aortic aneurysm (AAA) stent graft technologies to further expand its market leadership in China. In addition, MicroPort has also been able to expand to new markets, and perhaps in the future there will be opportunities to open the US market for both MicroPort and Lombard.

How do you see Lombard Medical’s products supporting MicroPort in the future?

MicroPort Endovascular is currently obtaining approval from the Chinese Food and Drug Administration (CFDA) for both of Lombard’s products, to open the China market. As Lombard continues to make progress in converting European key opinion leaders to Altura and Aorfix, this will also indirectly support commercial efforts in China as more and more EVAR surgeons globally become advocates for Lombard’s technologies.

What role do you think Aorfix and Altura can play in the broader endovascular device field?

Aorfix is indicated for procedures requiring high neck angles which occurs in approximately 20% of the abdominal aortic aneurysm (AAA) procedures. Aorfix has had a very long history of successful implantations with patients. Altura is also a very innovative AAA device that allows for same day procedures for aneurysm patients. We believe in the general device industry trends for more minimally invasive procedures with better efficacy outcomes for the patient, and that Altura can be the market leader for this type of procedures because of the benefits to patients and reduction in costs to hospitals.

What can we expect to see from Lombard going forward?

Firstly, the past is behind Lombard. The company has come out of its financial restructuring in 2018 in a much stronger financial position than it has ever been.

Hospitals and clinicians should feel comfortable that Lombard is here to stay. Secondly, Lombard should be even more competitive in the marketplace as the company is able to further reduce the manufacturing costs of its two products, thereby allowing more resources to be allocated towards investing and growing the top-line sales. Finally, with MicroPort as a strong strategic partner, we hope to further improve on Lombard’s existing portfolio and bring other great EVAR technologies from MicroPort Endovascular to the Western markets through Lombard.

European centres report promising Altura endograft experiences Four-year results of a clinical trial experience of 90 endovascular aneurysm repair (EVAR) patients treated with the Altura endograft system (Lombard Medical) were presented at the 2018 VEITHsymposium (13–17 November, New York, USA) by Dainis Krievins of the Pauls Stradins Clinical University Hospital in Riga, Latvia. The trial included the first-in-human implants, with the majority of recent cases performed using the commercial version of the graft.

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he trial pooled 90 patients with abdominal aortic aneurysms, enrolled between 2011 and 2015.

Patient demographics and anatomy were “typical for EVAR”, Krievins said, in terms of aneurysm size, neck length, and angulation. Patients were followed up with CT and clinical evaluation at 30 days, six months, and annually post-implant for up to five years (mean follow-up time in this report was 2.7 years). The CT images were evaluated by a core lab.

“We are all familiar with the complexities of EVAR which include complex aortic and iliac anatomies which frequently require complex devices to resolve them”, Krievins said. “Gate cannulation, snaring and polymer handling can lead to complex procedures of unpredictable duration.

This can make planning surgical lists around EVAR cases inefficient, impacting through and the overall costs of the procedure. The Altura stent-graft was designed to make EVAR cases a

little simpler for physicians and to give better predictability for the duration of the case.”

Krievins explained Altura uses materials such as nitinol and polyester fabric to create “a very differentiated stent graft construct in the form of kissing D endografts. These grafts are repositionable during deployment, do not involve gate cannulation and their 14F delivery systems all permit injection of contrast.”

Summarising clinical events at four years, Krievins stated: “Four patients were identified with Type 1 endoleak.

One patient died of unrelated causes before the leak was treated, a second case involved a substantial calcified nodule in the aortic neck and the leak did not extend into the aneurysm sac.

The remaining two endoleaks have not caused significant sac expansion.

At three years, the patent inferior mesenteric artery of a patient with a persistently expanding sac was embolised and bilateral distal extensions

placed. At four years, the under-sized grafts that were migrating were replaced by open vascular repair.”

Krievins concluded that the Altura endograft concept has the potential to play a “major role in mainstream EVAR cases”, offering an option for EVAR day-case practice as well as ruptured aneurysm patients.

David Murray (Manchester University NHS Foundation Trust, Manchester, UK) has taken part in a UKbased clinical experience study of Altura, which has reached its three-year mark.

Murray notes that in his centre, the Altura stent graft has been used in anatomically suitable patients within the indications for use only.

Outlining the results, Murray tells Vascular News, “there were no Type 1 endoleaks, or groin complications in the elective cohort. With

this experience the operative time was very low—less than one hour—with associated low screening (median 24 minutes) and radiation exposure (median radiation dose 3,058μGy). The majority of patients that were preselected for day-case achieved discharge in <24 hours.” With the system’s 14F profile, the majority of procedures at the UK centre were percutaneous, and more likely to be selected for day-case EVAR. The registry has recently opened a cohort to include day-case recruitment, which in time will analyse outcomes and potential cost benefits to this treatment modality.

For Murray, the Altura stent graft offers “the possibility of a simplified bimodular EVAR deployment on a 14F delivery system which, once adopted, will improve operative efficiency and provide cost-saving around inpatient stay.”

Altura Endograft System

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Peripheral interventions

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TOBA II trial data suggest clinically important treatment option for focal dissection repair after balloon angioplasty The Tack Endovascular System (Intact Vascular) can effectively repair peripheral arterial dissections after percutaneous transluminal angioplast (PTA) or drug-coated balloon (DCB) angioplasty, a study has found. William Gray from the Lankenau Heart Institute (Wynnewood, Pennsylvania, USA) conducted a pivotal trial that used the Tack device to treat patients with post-PTA dissections.

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ray presented the 12-month data from the Tack optimised balloon angioplasty study for postdissection repair of the superficial femoral and proximal popliteal arteries (TOBA II) at Vascular InterVentional Advances (VIVA; 5–8 November, Las Vegas, USA) during a late-breaking clinical trials session.

“Lesions with dissections have a target lesion revascularisation (TLR) rate up to 3.5 times higher than lesions without dissection,” explained Gray. However, current tools for dissection repair have limitations, and the Tack system is designed “to address stent drawbacks with a novel design to repair dissection post-PTA”.

The TOBA II study aimed to assess the efficacy of the Tack implant in repairing post-PTA dissections. “This is the first and only pivotal trial that has enrolled 100% dissected vessels”, Gray said at VIVA. Gray described the features of the device: “it has a deployed length of 6mm, self-sizing Nitinol allows it to fit vessel diameters 2.5–6.0mm, it has a unique anchoring system that minimises migration, and gold radiopaque markers enable visibility.”

Gray explained that by using the Tack system “multiple pre-loaded implants

can be placed using a single catheter and multiple dissections can be treated with a single delivery system”.

Comparing the differences between this device and a traditional stent, Gray outlined how “the Tack implant has a low radial force compared with a stent, resulting in much less inflammation and hyperplasia. It has a lower metal burden, with a stent requiring at least 70% more metal to treat the same length dissection.

It is also self-sizing between 2.5mm and 6mm, while a stent requires more precise sizing.”

Study design

The TOBA II trial was a prospective, multicentre, single-arm, non-blinded study in 33 sites in the USA and Europe, noted Gray. In the trial, a total of 213 subjects, all with post-PTA dissection (n=90) or Lutonix (BD) DCB angioplasty (n=123) were treated with the Tack implant.

The primary safety endpoint of the trial was freedom from the occurrence of any new onset major adverse events (MAEs) at 30 days (index limb amputation above the ankle, clinical events committee [CEC] adjudicated clinically driven TLR [CD-TLR] and all-cause death at 30 days). The primary efficacy endpoint was primary patency at 12 months (freedom

from CEC adjudicated CD-TLR and from core lab adjudicated Duplex ultrasound [DUS]-derived binary restenosis [PSVR ≥2.5]). Key observational endpoints were: freedom from CEC adjudicated CD-TLR; Tack performance, dissection resolution, migration and fracture; and changes in Rutherford, ankle brachial index (ABI) and quality of life measures.

To be included in the trial, patients had to have at least one Grade A to F dissection. Other inclusion criteria were a reference vessel diameter of 2.5–6mm, a de novo or nonstented restenotic lesion in the superficial femoral artery and/or proximal popliteal artery, the presence of at least one patent infrapopliteal vessel and post-PTA residual diameter stenosis (DS) ≤30%. Patients with previous bypass in target limb, acute/subacute thrombosis and/or occlusion, a post-PTA residual DS>30% or severe calcification were excluded.

Results

Gray noted that 43.2% of patients in the trial had diabetes mellitus, the average target lesion length was 74.3mm (±40.6) and the majority of patients had moderate (53.6%) or severe (5.7%) calcification.

“The TOBA II primary safety and efficacy endpoints were met, with 30-

Multiple stent delivery system proves “promising concept” in femoropoplital lesions A multiple stent delivery system (MSDS) to treat complex femoropopliteal lesions shows “promising results” at 12 months, according to data from the LOCOMOTIVE trial.

THE STUDY’S FINDINGS have been published in the journal Cardiovascular Interventional Radiology (CVIR), in which the researchers said: “Over a 12-month post-procedural period, MSDS for focal provisional stenting of complex femoropopliteal lesions demonstrated a promising primary patency and freedom from TLR [target lesion revascularisation]. In addition, significant improvements were observed in symptom classification and haemodynamics.”

With an MSDS, as many as six short 13mm stents per delivery device can be implanted. According to the investigators, this approach “enables focal stent implantations of multiple femoropopliteal segments … optimising procedural device handling”, compared to the use of shorter individual stents.

The efficacy and safety of the MSDS approach was investigated in LOCOMOTIVE (Multi-loc for flow limiting outcomes after POBA [plain old balloon angioplasty] and/or DCB [drug-coated balloon] treatment in the infrainguinal position with the objective to implant multiple stent segments), an all-comers, single-armed observational study conducted in high-volume German vascular centres. In all, 75 patients with symptomatic peripheral arterial disease were enrolled between July

2015 and July 2016, of which about one-quarter suffer from critical limb ischaemia (CLI). The primary endpoint was the rate of all-cause TLR at 6 months. Secondary endpoints were ankle-brachial indices (ABI), walking distance, and vessel patency rates at six and 12 months.

There were no device-related complications at baseline, and all stent segments could be implanted in the target lesions.

At 12 months, the primary unassisted patency was 85.7%, and all-cause TLR rate was 9.3% in the overall cohort. Between baseline and 12 months, the target leg ABI increased from 0.62 to 0.91 (p<0.001), and the mean Rutherford class improved from 3.5 to 1.9 (p<0.001).

LOCOMOTIVE’s six-month data has previously demonstrated a TLR rate of 5.3% and a patency rate of 90.7% in claudicants and CLI patients. There were four TLRs (5.3%) at six months, and seven (9.3%) at 12 months. The difference between six- and 12-month TLR was 4.0%. Between six and 12 months, neither target leg ABI nor Rutherford-Becker class changed significantly.

The study’s authors said: “Our strategy of combining balloon dilatation with focal stenting shows technical feasibility and safety of multiple focal stenting with MSDS, promising primary patency rates and freedom

day freedom from MAEs and primary patency at 12 months,” stated Gray, with “79.3% of all dissected vessels patent at one year and 86.5% of all dissected vessels free from CD-TLR at one year.”

Before undergoing Tack repair, “69.4% of subjects had a dissection of at least Grade C.” After the treatment, “92.1% of all dissections were completely resolved angiographically,” Gray explained. He described how the bailout stent rate was low, affecting only one patient in the trial.

In relation to clinical improvements, Gray said that the Rutherford clinical category improved by at least two classes in 63% of subjects, and the ABI, Walking Impairment Questionnaire and Peripheral Arterial Questionnaire all showed statistically significant improvements after Tack repair.

Gray summed up his presentation by stating that Tack was found to effectively repair dissections after POBA and DCB with minimal metal, a low radial force, a stable and durable design, and preservation of future treatment options.

“The high patency rate (79.3%) and high freedom from CD-TLR (86.5%) position Tack to be a clinically important treatment option for focal dissection repair after balloon angioplasty”, concluded Gray.

from TLR in all-comer lesions even after plain angioplasty, and favourable clinical results. Almost half of the lesion length could be saved from stenting, as compared to the full metal jacket strategy.”

However, they conceded that the absence of a control group limited the findings’ applicability. “Our study did not include a control group. Therefore, we cannot claim superiority of the multiple stent delivery system to other devices based on these results. A larger randomised trial or a properly propensity score matched patient population are needed to compare the focal stenting strategy to conventional interventions with long stents.”

The authors also said that allowing predilatation with DCB or plain angioplasty before stenting may have been introduced centre-effects bias, as “preferences for predilatations may have correlated with the procedural routines in vascular centres”.

They hypothesised that the common practice of bailout stenting of the full lesion length in cases of post-dilatation with flow-limiting dissection or recoil offers a “major advantage” to the MSDS system compared to single stent delivery systems, because of “the possibility to release up to six short stents without changing the delivery system”.

The investigators said: “We believe that the combination of balloon dilatation (plain balloon angioplasty or DCB) and/or atherectomy with (bailout) spot stenting might be a promising concept in calcified lesions and dissections.” In conclusion, they added that future studies comparing DCB and focal stenting on one side and DCB combined with long bare metal stents “will be crucial”.

“In addition, future studies with modern paclitaxelcoated peripheral stents … in the control arm, and drug-coated MSDS may also be a research avenue to be explored.”

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Aneurysm guidelines

New clinical practice guidelines for management of abdominal aortoiliac artery aneurysm: What is new and how does it differ from other guidelines?

Anders Wanhainen Gert Jan de Borst Comment & Analysis The first European Society for Vascular Surgery (ESVS) guideline on treatment of abdominal aortic aneurysm (AAA), published in the European Journal of Vascular and Endovascular Surgery in 2011,1 has had a major impact on clinical practice and research. However, due to the rapid developments of the field it has become outdated. In 2015, the process to update the ESVS AAA guideline was initiated. A writing committee consisting of 16 vascular surgeons from all over Europe worked out a comprehensive document, comprising 97 pages, including 790 references with a total of 125 recommendations. For the first time, ESVS guidelines were written in collaboration with patient representatives. The document has undergone three review rounds by 13 external reviewers from Europe, the USA, Asia and Australia, as well as by the 10 members of the ESVS guideline committee. The resulting â&#x20AC;&#x153;European Society for Vascular Surgery (ESVS) 2019 clinical practice guidelines on the management of abdominal aorto-iliac artery aneurysmâ&#x20AC;? were presented at the ESVS annual general meeting (25â&#x20AC;&#x201C;28 September, Valencia, Spain), published online in November 2018, and will appear in the January 2019 issue of the printed journal.2

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ere we summarise some news of importance to vascular specialists as well as policy makers, and briefly discuss notable differences between the ESVS guidelines and other contemporary guidelines; the Society for Vascular Surgery (SVS) AAA guidelines published in 2017,3 and the draft of the upcoming National Institute for Health and Care Excellence (NICE) aortic guideline targeting England and Wales.4 Level of evidence A

Data derived from multiple randomized clincal trials or metaanalyses.

Level of evidence B

Data derived from a single randomized clinical trial or large nonrandomized studies.

Level of evidence C

Consensus of opinion of the experts and/or small studies, retrospective studies, registries.

Service standard

The management of AAA has changed profoundly with the introduction of endovascular treatment. Studies have convincingly shown the benefit of endovascular aneurysm repair (EVAR) in both elective and emergency AAA repair in patients with suitable anatomy. At the same time, it is evident that some patients are not suitable for standard EVAR, or more complex endovascular treatment options, but should be offered open surgery. Consequently, one technique cannot entirely replace the other. Compromising the anatomical requirements for standard EVAR, using complex and partially experimental endovascular techniques to avoid established open surgical solution at all cost, or solely offering major open surgery when there are proven minimally invasive techniques, just because it is outside

office hours, is not in accordance with good clinical practice. Thus, today it is not acceptable to perform abdominal aortic interventions without the ability to offer both endovascular and open surgical technologies 24/7 (Recommendation 2; Class I, Level B).

The firm evidence of a volume-outcome relationship of surgery in general, and AAA repair in particular, makes it necessary and justifiable to make a recommendation on minimal surgical volume. No clear threshold was possible to identify in the literature, however. Various cut-off levels have been suggested,

and other aspects have to be taken into account, such as population density and geographical distances.

Based on the literature, the ESVS guideline writing committee (ESVS-WC) concluded that there is enough evidence for a rather weak recommendation on a desired minimum hospital volume of at least 30 cases annually (Recommendation 3; Class IIa, Level C) while a stronger recommendation can be issued on a minimum yearly case load of at least 20 repairs to perform aortic surgery at all (Recommendation 4; Class III, Level B). This is essentially in line with what the SVS recommends (an annual minimum volume of 10 cases for each open surgical repair and EVAR), and justifies a continued centralisation to medium and high volume centres. The NICE guidelines draft does not address this topic.

There are limited data concerning a reasonable waiting time for treatment once the threshold for repair has been reached. Although there is no strong evidence to support exact timings, it is reasonable to adopt a similar approach as for other life threatening diseases, such as cancer. Based on the rupture risk, as well as the psychological consequences, a suggested upper limit for the total pathway from referral to treatment is eight weeks, once the intervention threshold is reached. This applies, however, only to standard AAA cases, whereas in more complex aneurysms or comorbid patients a longer planning and/or work-up time is justified.

Correspondingly, a shorter time frame should be pursued for larger AAAs (Recommendation 5; Class I, Level C).

Those of us who fail to meet this requirement should promptly develop routines for fast-track pre-operative imaging and work-up. Modern cancer care often has well-structured treatment pathways with clearly defined deadlines, and may serve as a role model.

Elective AAA repair

Classes of recommendations

Definition

Suggested wording to use

Class I

Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, effective.

Is recommended/is indicated

Class II

Conflicting evidence and/ or a divergence or opinion about the usefulness/efficacy or the given treatment or procedure.

Class IIa

Weight of evidence/opinion is in favour of usefulness/ efficacy.

Should be considered

Class IIb

Usefulness/efficacy is less well established by evidence/opinion.

May be considered

Class III

Evidence or general Is not recommended agreement that the given treatment or procedure is not useful/effective: and in soe cases may be harmful.

Figure. The recommendations in the ESVS guidelines are based on the European Society of Cardiology (ESC) grading system

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Due to rapid technological and medical development, the existing randomised controlled trials comparing open surgical repair (OSR) and EVAR are partly outdated and thereby not entirely relevant for today’s situation. The evidence from randomised controlled trials (RCTs) also has the limitation that they mainly apply to patients <80 years of age, whereas today the greatest increases in AAA repair is among those >80 years. This group has also seen the most pronounced improvement in outcome after AAA repair, likely related to the preferential use of EVAR for treatment among octogenarians. It is therefore necessary to also include more recent case series and registry studies in the overall evaluation of the evidence base. Thus, despite data from multiple RCTs and meta-analysis, representing the highest level of evidence, we rate the existing level of evidence as mediocre (Level B).

Overall, evidence suggests a significant short-term survival benefit of EVAR over OSR, with similar longterm outcome up until 10–15 years of follow-up. Thus, in patients with suitable anatomy and reasonable life expectancy, EVAR should be considered as the preferred treatment modality (Recommendation 60; Class IIb, Level B). Yet, there are indications that increased rate of complications may occur after eight to 10 years with earlier generation EVAR devices and an uncertain durability of current devices, particularly the low profile devices. Thus, although EVAR should be considered the preferred treatment modality in most patients, it is reasonable to suggest an OSR first strategy in younger, fit patients with long life expectancy, i.e. >10–15 years (Recommendation 61; Class IIa, Level B).

These recommendations, which more clearly than before favour EVAR over OSR in most scenarios, differ significantly from the NICE guideline draft, where EVAR is not recommended at all in the elective setting.

It is obvious that the ESVS-WC has interpreted the literature completely differently, taking into account the fact that the RCTs comparing OSR and EVAR are outdated, while the NICE committee has not done the same assessment. The SVS makes no clear recommendation on the choice of surgical technique, but leave this decision to the individual surgeon, emphasising the importance of patient involvement.

Ruptured AAA repair

When pooled together, the one-year results of the three recent RCTs (IMPROVE, AJAX, ECAR) suggest that there is a consistent but non-significant trend for lower mortality post EVAR. The IMPROVE trial found faster discharge with better quality of life post EVAR, which therefore was cost effective. The recently published three-year results of the IMPROVE trial suggest that, compared with OSR, an endovascular strategy for suspected ruptured AAA was associated with a survival advantage, a gain in quality of life adjusted years, similar levels of reintervention, reduced costs, and this strategy was cost effective. These findings, together with observational studies and registry data, support a strong recommendation of an EVAR first strategy for ruptured AAA repair (Recommendation 74; Class I, Level B). This recommendation—a major change from the previous ESVS guidelines—is in agreement with both the SVS guidelines and the NICE guideline draft.

New devices

In recent years, manufacturers have developed new stent grafts and delivery systems with lower profiles to allow an endovascular approach even in patients with small access vessels. Although there are some series reporting favourable midterm outcomes for last-generation lowprofile stent grafts compared to standard profile stent grafts, more experience and longer-term outcome data, especially about the durability, are needed to confirm those findings. Therefore, when upgrades of existing platforms are used in clinical practice, the need for longterm follow-up should be recognised, and evaluation in prospective registries with complete follow-up is strongly recommended (Recommendation 57; Class I, Level C).

Aneurysm guidelines Novel new techniques and treatment concepts, such as endovascular aneurysm sealing with polymer-filled endobags (EVAS) has only been commercially available for a limited time, and their effectiveness and durability are still under investigation. We issue a strong negative recommendation of its use in clinical practice outside studies approved by research ethics committees and with informed consent from the patients, until adequately evaluated (Recommendation 58; Class III, Level C).

This approach is supported by recent alarming reports of higher-than-expected rates of leaks around the implant, device movement, and aneurysm enlargement after EVAS. Neither the SVS guidelines, nor the NICE guideline draft, address this topic, which we consider of great importance given the continued rapid industry-driven technical development. CE marking (or approval) is a certification mark for products sold within the European Economic Area (EEA), i.e. European Union (EU) and European Free Trade Association (EFTA).

Unlike the rigorous evaluation of efficiency and safety required for Food and Drug Administration (FDA) approval in the USA, CE marking has nothing to do with efficiency or safety. Thus, the role for several new innovative CE marked technologies on the market is still unclear and further data are needed before these can be recommended to be used in routine clinical practice.

Follow-up after EVAR

Due to the risk of graft-related complications and rupture after EVAR, regular imaging follow-up has been regarded as mandatory. The true value of prophylactic regular follow-up imaging after EVAR is uncertain, however.

Routine surveillance seldom identifies significant findings requiring reintervention, and most patients who require reintervention after EVAR present with symptoms.

Compliance with annual prophylactic imaging guidelines is suboptimal and lack of adherence to follow-up does not seem to affect long-term mortality or post-implantation rupture rate. Thus, annual imaging after EVAR for all patients is neither evidence-based nor feasible.

An early post-operative clinical and imaging followup after EVAR is required to assess the success of the performed intervention (Recommendation 91; Class I, Level B). Recent data suggest that patients considered at low risk for endovascular aortic repair failure after their first postoperative computer tomography angiography, i.e. no endoleak, anatomy within IFU, adequate overlap and seal of ≥10mm proximal and distal stent graft apposition to arterial wall, may be considered to be stratified to less frequent follow-ups, with delayed imaging up until five years after repair (Recommendation 92; Class IIb, Level C). Patients who do not meet these requirements should be assessed for the need for reintervention or continued frequent monitoring.

In contrast to the above approach with risk stratification, the SVS guidelines recommend continued annual imaging follow-up for all patients post EVAR. While the NICE guideline draft does not indicate a specific frequency for follow-up, it supports that it should be guided by the individual patients’ estimated risk of graft-related complications.

Juxtarenal AAA

Given the rarity and complexity of JRAAA treatment centralisation to specialised high volume centres that can offer both open and complex endovascular repair seems justified and is recommended (Recommendation 94; Class I, Level C).

Complex endovascular techniques have emerged as promising alternatives, or complement, to OSR for the treatment of JRAAA. However, reliable comparative and health-economic studies are still missing. Consequently, decision making is complex and should be tailored to each individual patient and local health economies.

Stratification of cases by anatomy and surgical risk may be useful in patients with JRAAA (Recommendation 95; Class IIa, Level C). OSR with an anastomosis below the renal arteries and short renal clamping time may be a

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preferable and durable option for fit patients with a short aortic neck. With more complex anatomy or high surgical risk due to comorbidities an endovascular solution may be preferable.

Despite limited data, it is the ESVS-WC assessment that fenestrated technology has a small advantage over parallel graft technique when it comes to proven feasibility and durability, as there are more multicentre reports and longer follow-up data available, and thus it should be the preferable endovascular technique for elective JRAAA repair (Recommendation 96; Class IIa, Level C).

Parallel graft techniques may, however, be considered as an alternative technique in the emergency setting or as a bailout (Recommendation 97; Class IIb, Level C), but one should then aim for a proximal landing zone of at least 15 mm, ensure a proper stent graft-oversizing of 30%, and use a maximum of two chimneys.

As for standard AAA repair, novel new techniques and treatment principles, such as EVAS, Endostaples and in situ fenestration are not recommended in clinical practice for JRAAA repair but should be limited to studies approved by research ethics committees and with informed consent from the patients (Recommendation 98; Class III, Level C).

Data is even more scarce for ruptured JRAAA, but the risk aversion is lower in such an immediate life threatening and complex situation. Therefore, in patients with ruptured JRAAA open repair or complex endovascular repair (with physician modified fenestrated stent grafts, off-the-shelf branched stent graft, or parallel graft) may be considered based on patient status, anatomy, local routines, team experience and patient preference (Recommendation 99; Class IIb, Level C).

JRAAA is not covered by the SVS guidelines, while the NICE guideline draft clearly recommend against any use of complex EVAR outside randomised clinical trials. Again, a big difference with potential huge clinical impact compared with the recommendations made in ESVS guidelines, and our views of the current knowledge are remarkably different. With today’s rather extensive experience of complex EVAR (especially fEVAR), showing generally good results, and the ability to offer treatment to many patients less suitable for major open surgery; it is difficult to motivate a strong preference for OSR over complex EVAR for JRAAA. Instead, we favour a more pragmatic approach, with OSR and EVAR complementing each other.

Conclusion

We encourage everyone to carefully read the new ESVS aortic guidelines document in its entirety.

It is an extensive document but offers many more recommendations of clinical importance (including recommendations on medical management, screening, iliac aneurysms, mycotic and inflammatory aneurysms, concomitant malignant disease, etc.) and a comprehensive supporting text that summarises the literature and motivates our positions. We hope you will find the document relevant and useful for your practice.

Anders Wanhainen is chair and corresponding author of the ESVS AAA Guideline Writing Committee. He is also professor of Surgery, Department of Surgical Sciences at Uppsala University in Uppsala, Sweden.

Gert J. de Borst is chair of the ESVS Guidelines Committee and professor of Vascular Surgery, Department of Vascular Surgery at University Medical Center Utrecht in Utrecht, the Netherlands.

References 1. Moll FL, et al. European Society for Vascular Surgery. Management of abdominal aortic aneurysms clinical practice guidelines of the European society for vascular surgery. Eur J Vasc Endovasc Surg 2011;41:S1e58 2. Wanhainen A, et al. European Society for Vascular Surgery (ESVS) 2019 Clinical Practice Guidelines on the Management of Abdominal Aorto-iliac Artery Aneurysms, European Journal of Vascular and Endovascular Surgery (2018), https://doi.org/10.1016/j.ejvs.2018.09.020 3. Chaikof EL, et al. The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm. J Vasc Surg. 2018 Jan;67(1):2-7 4. https://www.nice.org.uk/guidance/indevelopment/gid-cgwave0769/ documents

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Innovation

BIBABriefings

Medtronic leads European market for endovascular repair of infrarenal aneurysms

The BIBA MedTech Aortic Segmentation Monitor shows that, in Q2 (1 April–30 June), the Western European market for the endovascular repair of infrarenal abdominal aneurysms was worth US$62M and that Medtronic was the market leader with its Endurant II/IIs stent grafts (US$29.4M/47% of the market value). Gore, with its Excluder device (US$12.4M/20%) and Cook Medical with its Zenith devices (US$10.4M/17%) were second and third in the market respectively. See Figure 1.

Nearly 60% of aortic procedures performed in Q2 were for the management of infrarenal aneurysms, making them the most common presentation for an aortic procedure: 11,590 (57%) vs. 6,814 (33%) for thoracic aortic disease (aneurysm/dissections) vs. 2,075 (10%) for thoracoabdominal aneurysms (20,479 procedures overall). Furthermore, with infrarenal aneurysms, endovascular repair was the dominant approach—8,093 (70%) vs. 3,497 (30%) for open repair (11,590 overall).

Mixed results for new therapies presented at VIVA 18

At the 2018 Vascular InterVentional Advances (VIVA 2018) meeting (5–8 November, Las Vegas, USA), data for five new therapies were presented. While the data for the Venovo venous stent (BD Interventional), the Temporary Spur stent system (Reflow Medical), using an occlusion perfusion catheter (Advanced Catheter Therapeutics) to deliver paclitaxel, and the B-Laser (Eximo Medical) were promising, the data for JVS-100 (Juventas Therapeutics) did not show a benefit compared with placebo.

The aim of the STOP-PAD trial, which was presented at VIVA 2018

by Mehdi Shishehbor (Harrington Heart & Vascular Institute, University Hospitals, Cleveland, USA), was to examine the impact of complementary revascularisation therapy with intramuscular JVS 100 compared with placebo. According to a VIVA 2018 press release, JVS-100 is a “non-viral gene therapy that activates endogenous regenerative repair pathways on wound healing”.

The primary efficacy endpoint was six-month wound healing and the primary safety endpoint was major adverse limb events. Among 109 patients

enrolled in the study (all with critical limb ischaemia), only 32% of wounds completely healed at six months with no differences between three groups evaluated (8mg JVS-100, 16mg JVS100, and placebo). There were also no significant changes in toe branchial index at six months. The conclusion of the study, the press release notes, was that “although safe, JVS-100 failed to improve wound healing or haemodynamic measures at six months”.

By contrast, the VERNACULAR trial showed that the Venovo venous stent could be deployed successfully in obstructive iliac and femoral vein lesions with a 12-month primary patency rate of 88.3%, the DEEPER study showed that the majority of patients treated with the Temporary Spur stent system (in conjunction with a drug-coated balloon) for the management of below-

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Choice of repair approach depends on type of thoracoabdominal aneurysm

Overall, the endovascular approach was the dominant repair method for thoracoabdominal aneurysms: 1,072 (52%) vs. 1,003 (48%) for open repair (2,075 overall). However, this did change depending on the type of thoracoabdominal aneurysms. For example, open repair was the most common repair approach used for juxtarenal aneurysms (369 [51%] vs.

361 [49%], 730 overall), but endovascular repair was the most common approach for type IV aneurysms (236 [64%] vs. 131 [36%], 367 procedures overall). See Figure 2.

Of note, juxtarenal aneurysms represented the most common presentation of thoracoabdominal aneurysms in Q2 (730 of 2,075 procedures overall) while type V (80 of 2,075) were the least common presentation. For all presentations, Cook Medical was the market leader (US$8M/35%) and the overall market was worth US$14M.

the-knee lesions saw an improvement in clinical outcomes at six months, and the six-month results from the COPPER BTK cohort showed that using a novel occlusion perfusion catheter that administers liquid paclitaxel after percutaneous transluminal angioplasty was associated with a primary patency rate of 85.7% at six months in patients with peripheral arterial disease.

Additionally, John Laird (UC Davis Health System, Sacramento, USA) presented results for the B-Laser for the treatment of infrainguinal peripheral arterial disease. The press release describes the laser as a “novel atherectomy device using an array of optical fibres transmitting short pulses

BIBA Briefings

of 355nm waves surrounded by a blunt blade”.

In the study of 50 patients with peripheral arterial disease (with a total of 53 B-Laser treated lesions), clinical success was achieved in 100% of lesions. The press release states “core lab evaluation of baseline stenosis, post B-Laser and residual stenosis, and average reduction in stenosis post B-Laser were 93.6% ±13.6%, 58.7%±15.1%, and 35.04%±14.78%, respectively”.

Therefore, the conclusion of the study was that the B-Laser technology was a promising technology for atherectomy of complex heterogeneous lesions. The laser received FDA approval in October 2018 and is CE marked.

BIBA Briefings is a new platform that provides in-depth analysis of the latest market intelligence from BIBA MedTech Insights, which provides consulting and market analysis services to medical professionals and organisations in the medical device industry in Europe and North America.

The platform also reviews data and news.

The aim of every each report report isis to to give give an an overview overview of of the the key key information information affecting the medical device industry, enabling those working in the industry to keep abreast of the latest developments and make knowledgeable decisions.

For more information about BIBA Briefings or BIBA MedTech Insights, please contact Laura James at laura@bibamedical.com laura@bibamedical.com

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Conference coverage

Drug-coated balloon trial highlights under-representation of women in peripheral arterial disease revascularisation studies Data from a study that compared the use of the Stellarex (Philips) drug-coated balloon (DCB) to treat femoropopliteal arterial disease in men and women were presented by Maureen Kohi, from the University of California (San Francisco, USA) at Vascular InterVentional Advances (VIVA; 5–8 November, Las Vegas, USA) during a late-breaking clinical trials session. Despite having older age and worse vessel and lesion characteristics, the study found that women had similar patency outcomes to men following treatment with the Stellarex DCB. According to Kohi, the study further highlights a need to examine enrolment of women into peripheral arterial disease DCB trials.

“PERIPHERAL ARTERIAL DISEASE (PAD) affects 5 to 10 million people in the USA and the prevalence of PAD in women is at least the same as in men, if not higher,” Kohi said at VIVA. However, despite the fact that women have a longer life expectancy than men, and will be more disproportionately affected with PAD in the future as the population ages, Kohi explained that “PAD remains underdiagnosed in women, and women are underrepresented in contemporary PAD revascularisation studies.”

With regard to studies that examine DCBs, the evidence is mixed in women, “with lower success rates reported in females versus males treated with DCBs (THUNDER, LEVANT II); while one- and two-year results from the IN.PACT SFA trial showed significant benefit with IN.PACT Admiral DCB (Medtronic) over plain angioplasty in both females and males. But there continues to be a need for evidence on the effectiveness of DCBs in females,” stated Kohi, thus prompting this study.

Kohi outlined how a subgroup analysis of the DCB cohort of the EU and US ILLUMENATE trials aimed “to evaluate for sex-related differences in the outcomes of the Stellarex DCB for the treatment of femoropopliteal arterial disease.”

A total of 418 patients were included in the analysis: 269 men (64%) and 149 women (36%). The primary efficacy and safety at 12 months were compared between men and women, and a multivariable predictor analysis was performed to identify predictive factors for patency.

Kohi described the structure of Stellarex DCB,

vessel diameter was shown to be smaller in women than men. Lesion lengths were found to be longer in women than in men.” As regards procedural characteristics, “the total fluoroscopy time was longer in women. The vessel diameter after DCB was smaller in women than men. As expected, adverse events (primarily dissections) were higher in women than in men”, continued Kohi.

Results

Maureen Kohi

which “has a low dose of paclitaxel (PTX) in a hybrid formulation with amorphous PTX that improves coating stability and provides prompt drug availability, while crystalline PTX gives sustained drug release into tissue.

A polyethylene glycol (PEG) excipient has a high affinity towards hydroxylapatite, which may limit PTX washout in the presence of calcified lesions.”

Compared with standard PTA, Kohi said that Stellarex DCB has shown better results for primary patency and lower CD-TLR at 12 months in both men and women.

Kohi described the patient characteristics in the analysis as being similar “except that women were significantly older than the men in the study”. In terms of lesion characteristics, Kohi said “we know that women have smaller blood vessels and the reference

Kohi reported that the 12-month primary patency rates were similar between the two groups, “with 81.7% primary patency in males vs. 78.8% primary patency in females (p=0.48).” Twelve-month CD-TLR was 5.2% in males vs. 9.9% in females (p=0.078) and Kohi stated that “although the result was not statistically significant, it shows a directional shift.”

The only predictor of primary patency common to men and women was previous study limb intervention.

Predictors of primary patency particular to men were found to be having a larger vessel diameter, having less calcification and not having geographic miss, while the only predictor particular to women was having smaller lesion lengths.

Kohi concluded that “women and men have different risk factors and predictors of primary patency. Even though women in the study were older and had worse vessel and lesion characteristics, they had similar patency outcomes to men following treatment with the Stellarex DCB.” Further evaluation of the efficacy of DCBs is therefore needed “to understand the disparate nature of the disease progression and to optimise treatment outcomes in women with PAD”.

Outcomes of the ANCHOR registry show consistent outcomes for endoanchors at three years Real-world outcomes in patients from the ANCHOR registry at three years show safe and effective performance of the Heli-FX EndoAnchor system (Medtronic) in complex abdominal aortic aneurysm (AAA) anatomy—particularly in hostile aortic neck anatomies.

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illiam Jordan presented threeyear data from the registry at the VEITHsymposium (13–17 November) in New York, USA. Jordan is professor of surgery and chief of the Division of Vascular Surgery and Endovascular Therapy at Emory University School of Medicine (Atlanta, USA) as well as the co-principal investigator of the ANCHOR registry.

The clinical evidence demonstrated the Heli-FX EndoAnchor system provides additional security when used with approved endovascular stent grafts in patients with hostile infrarenal AAAs. The ANCHOR registry is a prospective, multicentre international study involving sites in the USA and

in Europe, to evaluate the real-world utilisation for EndoAnchors in patients.

The registry aims to enrol 2,000 patients, with the three-year data so far including 800 patients treated for AAA with Heli-FX in combination with a graft (primarily from Medtronic, Gore, Cook or Jotec).

The majority of patients enrolled received EndoAnchor implants prophylactically, while a smaller group received them following a previously failed endovascular repair (EVAR) treatment (therapeutic revision). The data presented today includes a subset of patients from these groups who were eligible for clinical and imaging followup at three years.

William Jordanx

Patients had short, hostile neck anatomies with median neck lengths of 11.2mm in the prophylactic group, and 10.2mm in the therapeutic revision group. Specific results through three years include: Low rates of Type Ia endoleaks: 1.7% prophylactic (2/120) and 2.4% therapeutic revision (1/41) at three years.

Positive sac stability and regression despite the hostile anatomy characteristics: 96.5% prophylactic (111/115) and 80.0% therapeutic revision (32/40) at three years.

High rates of freedom from secondary procedures to treat Type Ia endoleak based on Kaplan-Meier estimate: 98.7% prophylactic and 86.3% thera-

peutic revision through three years.

High rates of freedom from aneurysm-related mortality (ARM) based on Kaplan-Meier estimate, which is notable given the short neck lengths: 98.3% prophylactic and 91.1% therapeutic revision through three years.

“Hostile aortic necks are frequently seen in clinical practice and have historically presented challenges for physicians treating patients through an endovascular approach,” said Jordan. “With these data, we are continuing to validate that by using Heli-FX in these challenging cases, we have the ability to successfully treat this critical patient population and expand applicability of EVAR to those with complex aortic anatomies.”

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Advertorial

SPONSORED BY LOMBARD MEDICAL

The case for day-case EVAR: Benefits and challenges Endovascular aneurysm repair (EVAR) is an established treatment modality in vascular practice which continues to develop, as new devices and technology continuously provide a greater range of options for the treatment of aneurysm patients. Implementing day-case EVAR into practice can further enable clinicians to increase patient satisfaction and quality of life.

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achel Bell, a vascular surgeon at Guy’s and St Thomas’ NHS Foundation Trust (London, UK), notes that “in general, most patients and their families prefer a day-case procedure, as they would like to be able to recover in the comfort of their own home.” Bell adds, “Lots of patients have worries about spending time in hospital, and being able to go home at the end of the day allay these concerns and improves their quality of life.”

Beyond the comfort of the patient, Bell also points to “obvious clinical benefits” including reduction in hospital acquired infections and reduction in the incidence of deep venous thrombosis or pulmonary embolism, which can occur as patients stay immobile in the hospital. “There is no doubt,” Bell says, “that day-case procedures encourage patients to be more mobile after surgery and help them to recover more quickly. It is common for older patients to suffer some functional decline when they have been an in-patient in hospital, and day surgery would go some way to reducing that and encourage patients to get back to normal life as quickly as possible.”

Grainne Nicholson, vascular anaesthetist at St George’s University Hospitals in London, UK, agrees: “Provided the selected patients were informed about what to expect and reassured that their care will be of the highest standard, day-case EVAR may improve patient satisfaction and quality of life. In general, patients prefer to be at home rather than in hospital.”

Nicholson further points out, “Implementation of a day-case EVAR process could potentially improve service provision, as the whole in-hospital process is streamlined, suitable patients are identified, operated on early and discharged early. Reducing the length of time any patient spends as an in-patient will have a direct cost-saving effect.”

This impact on cost as well as efficiency is an important factor, particularly in centres where bed space is a rare resource. For vascular surgeon David Murray (Manchester University NHS Foundation Trust, Manchester, UK), the main benefit of day-case EVAR is the “reduction in requirement and cost for high dependency or monitored bed days and in-patient bed days per case.” Similarly, Bell acknowledges there are “enormous pressures on most hospitals’ bed capacity, particularly over the winter months”, a problem which can be alleviated with the implementation of day-case EVAR. “However it is necessary to ensure that we provide appropriate support for the day-case patients to ensure that they are safe and appropriately supported at home, with good lines of communication to the hospital team if required”, Bell says.

Patient selection

Murray and Nicholson both place an emphasis on the importance of patient selection for day-case EVAR, with Murray arguing that patient education is paramount. He explains, “We select patients for

day-case EVAR on a number of parameters. We select anatomically straightforward abdominal aortic aneurysms for EVAR, with good access and friendly common femoral arteries for percutaneous EVAR. We exclude chronic kidney disease stage 4 and 5 patients, and patients with more than 30 minutes’ travel time to the hospital. Selected patients must also buy in to the concept and be motivated. We offer local and general anaesthesia depending on patient preference and always have the day-case EVAR as first patient on the list. If necessary, the patient can stay overnight to be discharged early next day, with less than 24 hours’ total in-patient stay.”

Nicholson similarly believes that the key issues to introducing successful day-case EVAR into practice are “careful patient selection, both with regard to the patient’s attendant co-morbidities and the anticipated complexity of the procedure as well as comprehensive preoperative assessment so that all investigations are carried out and reviewed to determine if the patient is indeed a suitable day-case candidate. Patient information and education is also important so that the patient is involved in the decision-making process and knows what to expect.”

In setting up a day-care EVAR practice, Bell adds: “It is really important that the new pathway is discussed with all stakeholders so that everyone is on board with the changes—that there is no tendency to revert to the in-patient pathway.”

Five-year PYTHAGORAS results with Aorfix stent graft in highly angulated necks The outcomes at five years of the Aorfix (Lombard Medical) PYTHAGORAS trial, published in the Journal of Vascular Surgery, provided the first long-term data from an endovascular aneurysm repair (EVAR) cohort to include a majority of highly angulated infrarenal necks. Vascular News spoke to investigator Mahmoud Malas about the trial and the implications of its findings.

What risks, difficulties or complications have typically been associated with EVAR in highly angled aortic necks?

Highly angled aortic necks (≥60° angulation between infrarenal aortic neck and the longitudinal axis of the aneurysm) increases EVAR complexity by making it difficult to introduce the delivery system and deploy the stent graft. It is also associated with several postoperative complications. More recent data have shown an association between difficult aortic anatomy and decreased long-term survival.

How does the Aorfix endograft design address these issues?

The Aorfix endograft is designed to be flexible and conformable to the vessel which makes it particularly suitable when proximal and/or distal landing zones are considerably angulated. It

employs polyester graft material surrounded by independent nitinol rings, rather than Z stents, allowing the device to conform to the angulation of the native aorta without collapsing, and be resistant to kinking. Four pairs of hooks proximal on the graft are attached within an 8mm primary sealing ring to allow transrenal fixation. When implanted, the stent graft rings reform to a saddle or “fish mouth” shape, hugging the renal artery orifice and allowing the endograft to be placed pararenally. Moreover, the troughs align with the renal arteries juxtarenally and the peak extends suprarenally, providing optimum seal positioning and reducing risk of endoleaks.

How was the PYTHAGORAS trial designed?

The PYTHAGORAS trial is the first clinical trial designed to test the use of EVAR for highly angulated (≥60°)

Mahmoud Malas

aortic necks. It is a multicentre (45 institutions), non-randomised regulatory study approved by the US FDA. The study enrolled 218 patients for an Aorfix procedure divided into two groups: standard aortic neck angulation (<60°) and highly angulated aortic necks.

Patients were followed up for a total of five years. Postoperative imaging studies (CT scans and abdominal radiographs) were reviewed to assess all components of the primary efficacy endpoints including all-cause or aneurysm related mortality, endoleaks, rupture, reintervention and graft migration.

What were the results of the trial at five years, and what data did you find noteworthy?

I believe that the most interesting findings from the PYTHAGORAS study is that it is the first clinical trial to include patients with highly angulated

aortic necks (69%), who would be deemed at high risk for EVAR with other endovascular aortic devices.

The results are favourable and support the use of this on-label endovascular option. Freedom from all-cause mortality (69%) aneurysm-related mortality (96%), secondary intervention, and aneurysm rupture rates over five years were comparable with the Lifeline Registry of United States EVAR trials in normal anatomy and were found to be equivalent to other endografts used to treat normal anatomy. Moreover, the five-year sac expansion rates (12%) were lower than those of prior studies.

The trial also reported no differences in the rate of type I/III or type II endoleaks or need for reinterventions with Aorfix among patients with standard-angle versus highly angulated aortic necks.

How do you think these results may impact practice, and what questions remain to be answered?

The use of the Aorfix has increased the number of patients eligible for EVAR, who were previously excluded from this type of treatment. However, it is important to note that the success of EVAR using the Aorfix depends on a combination of factors, including good patient selection, careful planning using multi-planar CT imaging, and appropriate graft sizing. Follow-up beyond five years in these patients might be interesting.

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Section Name

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Low embolisation risk with micromesh carotid stents

Patients treated with either the Roadsaver (Terumo) or the CGuard (InspireMD) micromesh carotid stents had similar low risk of embolisation following carotid artery stenting at one Italian centre. The results were presented by Maria Antonella Ruffino (San Giovanni Battista University Hospital, Turin, Italy) at VEITHsymposium (13–17 November, New York, USA).

THE DATA ARE FROM a prospective, single centre study of 50 consecutive patients implanted with micromesh stents (Roadsaver and CGuard) for carotid artery stenosis. The study sought to identify plaque activity at baseline using a diffusion weighted (DWI) magnetic resonance (MR) scan, and to evaluate the real incidence to new ischaemic lesions related to the interaction between the plaque and the two micromesh stents (plaque remodelling), with a DWI MR scan one hour after carotid artery stenting.

Investigators also wanted to identify whether there is a relationship between plaque activity (as demonstrated by DWI MR) and new ischaemic brain lesions at 24 hours after stenting with either micromesh stent, and whether DWI MR plaque positivity can predict the risk of new ischaemic lesions after CAS and so helping to identify high-risk patients.

Ruffino reported no significant difference between the two stents in terms of outcome following carotid artery stenting. One hour following stenting the Roadsaver stent group had zero incidences of new ischaemic lesions and the CGuard group had three (p=0.23). After 24 hours, the DWI MR scans showed that the Roadsaver group had six incidences of new ischaemic lesions and the CGuard group had 10 incidences (p=0.36).

Overall after 24 hours, new ischaemic lesions were found in 38% of patients (19/50) with a total of 34 lesions (1.79 lesions per patient) and 82% (28/34) of those new ischaemic lesions were ipsilateral. The majority of new ischaemic lesions (88.2%) appeared after 24 hours, while only 12% (4/34) appeared at the one-hour post-procedure scan.

Ruffino explained that while the study found no difference in terms of which carotid stent was used as it relates to the risk of embolisation, they did learn something about plaque activity. She explained that plaque activity can be easily and promptly evaluated by DWI MR and, when positive, it is predictive of a higher risk of new ischaemic lesions at 24 hours following carotid artery stenting (LR+ 6.26, p<0.0001).

All patients enrolled in the study underwent Doppler ultrasound at six, 12 and 24 months to evaluate in-stent restenosis and new external carotid artery stenosis or occlusion. Ruffino reported that again, there was no significant difference between the stents used. At 24-month follow-up, in-stent restenosis was recorded in 10% of patients (5/50, with one occurring at six months and four at one year)—three in the Roadsaver group and two in the CGuard group (p=0.19). In terms of new external carotid artery stenosis, Ruffino said that it was found in 4% of patients (2/50), all of which occurred

in the Roadsaver group at six months follow-up.

Comparing their work with that of a meta-analysis of restenosis after carotid interventions and its relationship with recurrent ipsilateral stroke (Kumar et al, Eur J Vasc Endovasc Surg 2017), Ruffino indicated that the rate of instent restenosis was the same—10%.

Similarly, compared to conventional carotid artery stenting (Brown et al,

Journal of Vascular Surgery 2013), Ruffino’s series had 0% external carotid artery occlusion and 4% external carotid artery stenosis, while conventional carotid artery stenting mentioned in Brown’s work was associated with a 3.8% rate of external carotid artery occlusion.

Ruffino concluded that if these findings are confirmed by a larger cohort of patients and long-term follow-up, it

can be said that the incidence of in-stent restenosis and external carotid artery stenosis following carotid artery stenting with micromesh stents is consistent with what has been reported for conventional carotid artery stents. She added that no difference was found between the two micromesh stents and that these stents may exert intrinsic embolic protection and impact positively on carotid artery stenting outcomes.

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Vascular scoring systems

Assessing the “danger” of over-reliance on vascular scoring systems Speaking on the topic of whether a reliance on scoring systems in vascular surgery can be harmful for patients and surgeons, Chris Twine, a consultant vascular surgeon at North Bristol NHS Trust, Bristol, UK, argued that although such systems can outperform surgeons, individualise care, and assist in decision making, they may be harmful or even “dangerous”, especially if used for morality prediction. This conclusion was recently presented at the Vascular Society’s Annual Scientific Meeting (28–30 November, Glasgow, UK).

PRESENTING A SERIES of papers to the audience, Twine pointed to the fact that while some guidelines suggest using patient risk assessment tools, others deduce the opposite, or that standardised systems documenting the severity are more useful. Attempting to disentangle the literature, Twine contrasts a classification system, defined as “A system describing a clinical situation, such as Rutherford, with no prognostic implication”, with a true scoring system; “Those generated in the first place to hold prognostic information and aid decision making—to essentially try and help physicians do their job”. Yet, to achieve the latter, the scoring systems must be both reliable and valid.

In terms of their utility, Twine pointed to previous work he was involved with, regarding a systematic review of surgeon’s assessment of risk (across all surgical specialties), compared to the use of scoring systems. The investigation, inclusive of 27 studies, 20,989 patients and multiple outcomes, led Twine to conclude: “In some situations, they [scoring systems] can outperform our clinical assessment, while in other circumstances they are equal to us. However, they are almost never worse than us, when you look at the literature.” Offering a reason as to why, Twine said

“We, as surgeons, overestimate risk, especially in the case of mortality. If we have early negative experience of patients dying, there is evidence that we go on to overestimate the risk of that procedure for the rest of our career.”

Nevertheless, Twine addressed the issues surrounding the reliability of scoring systems. While he stated that there are no major problems with reliability specific to vascular surgery, he stated that confidence intervals, which come with all risk prediction percentage risks, are unacceptably wide for some prognostic values and seem to be continually ignored. Secondly, Twine acknowledged that alongside the digital growth of society, a specific problem with scoring systems on phone apps has arisen. He gave the example of the Wifi scoring system: “When this system was shrunk into the app, definitions lack the detail they have in the literature which means the operator may unknowingly choose the wrong definition of for example, a shallow ulcer.”

Regardless of this issue, Twine surmised “Overall, I would not say that reliability is a huge issue; validity is a bigger issue.”

According to Twine, both expert opinion and regression modelling from retrospective data allow for the assessment of construct validity of scoring

systems. Additionally, criteria-related validity is subsequently evaluated, ideally by looking at the predictive validity of a scoring system within another dataset, then by addressing its discriminant validity through comparing it with others.

Although Twine Chris Twine acknowledged data indicative of promising outcomes for predictive validity through modern techniques for expert opinion, he pointed to the fact that regression modelling is a more common means of assessment throughout vascular surgery. In contrast with the Hardman score—a scoring system for ruptured aneurysms generated from 136 patients in the 1980’s—the more recently Ambler AAA (abdominal aortic aneurysm) score (The Cambridge Group), was generated using ‘big data’ based on 8000 ruptured aneurysms from the national vascular registry treated in the UK. In order to assess the latter system, researchers applied several models to over 2,500 patients and found that the Ambler AAA model came out on top, in terms of both predictive validity as well as discriminant validity.

Yet, Twine postulated that a scoring system generated from a particular dataset will always validate well in a similar patient dataset, but not necessarily in an alternate dataset. However, regardless of a paper from

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the IMPROVE trial concluding that predictive validity varies quite markedly between different patient datasets and therefore patients, Twine said: “With big data now available, construct validity should continue to get better with time.”

Nevertheless, Twine maintained that scoring systems are not good enough for use in a mortality setting, and further stated that he was in agreement with the National Institute for Health and Care Excellence (NICE) guidelines recommending against the use of scoring systems to determine whether aneurysm repair is suitable for a person with a ruptured AAA. “The reality is even more complicated, as it is not just about whether the patient is to live or die given a particular circumstance, it is about quality of life, discharge to home, and patient choice”, said Twine.

Therefore, in conclusion on whether scoring systems in vascular surgery are useful or dangerous for patients and surgeons, Twine elucidated: “They can outperform

us, individualise care, and assist in decision making [...], but in certain circumstances, their use can be dangerous, and while there is no perfect scoring system applicable to all patients, some are far better than others”. Further, Twine noted that they are generally more useful in elective settings where results can be carefully discussed with patients. In terms of moving forward with scoring systems in vascular surgery, Twine maintained that the evolution of expert opinion alongside the use of randomised and big data means that their validity and influence will only continue to improve.

Following the presentation, members of the audience questioned whether a scoring system with the ability to remove all uncertainty will ever be generated. In response, Twine said that it would be more beneficial to validate existing scoring systems and work on using them more effectively—as opposed to generating new ones. Another audience member questioned whether surgeons should stop quoting an absolute risk

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altogether, to which Twine replied that presenting the best predictive figure to patients alongside the national figure and the associated unit figure is good enough, and valid. “Not, however, for mortality prediction in an emergency setting”, he emphasised.

A further audience member highlighted the fact that there are two aspects that scoring systems should take into account: patient fitness in terms of how long it takes to get from table to hospital bed, but also how long the patient will benefit from a particular intervention. “Taking into consideration how long a patient is predicted to survive with or without the intervention is important”, the audience member proclaimed. In agreement, Twine said that this consideration, as well as other aspects of quality of life are often more important to the patients than the “binary live or die.” Although Twine said that scoring systems are not yet able to assess both of these aspects, he surmised that as these systems evolve, they should

Endovascular resuscitation and trauma management: Vascular surgeons and interventionalists should take the lead Tal Hörer Comment & Analysis In the last 20 years, there have been major developments in the use of endovascular and hybrid haemorrhage control tools, especially in the treatment of ruptured abdominal aortic aneurysm (rAAA).

I

t has been shown that total endovascular aortic repair (EVAR) for rAAA is feasible, with good results from the use of endovascular and hybrid methods and tools (Mayer et al. Annals of Surgery 2012). Use of embolisation, endografts, balloons and other tools for bleeding control has grown rapidly as well, and these methods are now also being used for gastrointestinal, tumour, iatrogenic and medical bleeders and post-partum bleedings. Endovascular methods developments have not been limited to bleeding patients, but also expanded to other fields, with the use of extracorporeal membrane oxygenation (ECMO) and the evolving eCPR concept for cardiac arrest. The collection of tools described here can be subsumed under the recently established concept of endovascular resuscitation and trauma management (EVTM). It requires a multidisciplinary platform on which surgeons, vascular surgeons, interventionists and ICU and trauma surgeons work together on the unstable patient from arrival to the achievement of effective haemorrhage control and resuscitation. Indeed, the use of endografts for traumatic thoracic aorta bleeding, and bleedings in subclavian and other major vessels, is in use today in trauma, as it is in embolisation for visceral bleedings and pelvic bleeding in trauma patients resuscitative endovascular balloon occlusion of the aorta (REBOA), or aortic balloon

occlusion (known as ABO, or I-ABO), has been used for many years in vascular surgery, and is a part of the endovascular arsenal, with a crucial role in unstable patients with rAAA. In the last eight to 10 years, endovascular techniques including REBOA have expanded into trauma surgery, with major application to patients with non-compressible torso haemorrhage (NCTH) in both the hospital and an austere or military environment. NCTH is a major cause of death, both in civilians and from military injuries, and an open-surgery approach and damage control have for many years been the gold standard. Lately, with increasing use and limited reports and studies, REBOA has gained popularity (and also given rise to substantial controversy) in the trauma world.

REBOA has now been adopted in some practical trauma guidelines; and, for example, pelvic traumatic bleeding has, to some extent, replaced thoracotomy or laparotomy and open aortic clamping (figures 1 and 2). While endovascular technology evolved in the last 10 years, imaging has also undergone tremendous developments. Computed tomography (CT), ultrasound, hybrid suites and other imaging modalities have become faster and more accurate, specific and accessible in many centres. Historically, just several years back, CT may have been regarded in the trauma world as “the tunnel of death” due to long scanning time and availability as well as

its location. It is still a common belief and praxis that embolisation neecessitates transfer of the patient and long procedure times. The introduction of EVTM multidisciplinary collaboration, as well as modern endo tools and imaging, hybrid suites and the emerging CT-onrails and hybrid ER, now allows the fast use of minimally invasive methods, immediately on patient arrival, in one place with minimal delay.

The EVTM concept is still developing, and hard data supporting its benefits have not yet been presented. In some areas in trauma, however, the use of minimally invasive tools is clearly supported by data, as in the cases of treatment for thoracic aortic injuries and embolisation for pelvic bleeding (as mentioned above). REBOA for NCTH is not yet established, and, so far, there are no prospective randomised data to support its widespread use. As EVTM develops to include also no-bleeders and resuscitation, there is a great need for the multidisciplinary evaluation and implementation of methods such as REBOA and ECMO, as other endo or hybrid techniques. There are some ongoing studies that we hope will supply firmer data in the coming two years. There is also massive work on the development of the EVTM concept and its recognition. This has been achieved partially by the EVTM symposiums (four meetings done by Dec 2018, with two more planned for 2019), workshops, seminars, registry studies, animal studies, multicentre studies and the Journal of Endovascular Resuscitation and Trauma Management (JEVTM), as well as by the expanding EVTM community. All the activities have aimed at sharing and gathering data to support medical practice and science.

The motto of the EVTM movement is simple: “no ego, just good science and cooperation”. Vascular surgeons and interventional radiologists should play the leading role in using these methods clinically as needed, and in the gathering and sharing of data to support or reject their application to our patients.

Tal Hörer is a Vascular and General surgeon at the Örebro University hospital in Örebro, Sweden, founder of the European EVTM Symposium, and editorin-chief of JVETM.

Figure 1: REBOA in three different zones: Zone I supraceliac (or descending) aorta, Zone II para visceral, and Zone III infra-renal. Partial REBOA (pREBOA) or intermitted REBOA (iREBOA) can be used for haemodynamic stabilisation in a wide range of instabilities, as a bridge to definitive treatment.

Figure 2: Zone-I REBOA in a trauma patient on a CT scan. Partial balloon occlusion (pREBOA) was used in this patient and contrast media is seen distally to the balloon. pREBOA can be used for blood pressure control while maintaining some perfusion distal to the balloon and bleeding localisation on CT.

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Product News Tack Endovascular System launches in the EU with first commercial use in Germany

The first commercial use of the Tack Endovascular System (Intact Vascular) has taken place in multiple hospitals within Germany. A novel therapy for dissection repair following balloon angioplasty, the Tack implant is a first-of-its kind device for patients with peripheral arterial disease (PAD) and/or critical limb ischaemia (CLI).

“The Tack System provides a much needed therapeutic option for treating dissections in the superficial femoral or popliteal arteries following balloon angioplasty,” says Christian Wissgott, assistant director at Westküstenklinikum Heide in Heide, Germany. “I am very pleased with my experience using the implant and I am excited to incorporate this technology into my above and below the knee treatment algorithms going forward.”

Patients treated with balloon angioplasty frequently suffer from dissections. Often overlooked, undiagnosed and untreated, dissections can lead to acute thrombosis and arterial occlusions, which lower longterm patency rates and require repeat procedures. Designed to resolve these dissections while leaving minimal metal behind, the Tack implant is designed to preserve vessel integrity, minimise vessel inflammation and enhance blood flow.

“With the Tack System, balloon angioplasty results are improved regardless if it is drug-eluting or not,” notes Michael KW Lichtenberg, chief of the Angiology Clinic and Venous Center in Klinikum Arnsberg, Germany. “Based on my initial experience, I am confident this new paradigm of focal dissection repair will become standard of care for patients undergoing PAD interventions.”

This follows the recent news that the Tack Optimised Balloon Angioplasty II below-the-knee (TOBA II BTK) clinical trial has successfully completed enrolment, ahead of schedule.

Unrestricted sales of the Nellix System to cease as use is limited to current indications

Unrestricted sales and use of the Nellix System (Endologix) will cease immediately, in order to ensure optimal outcomes for patients, according to Endologix. The product will only be available for use under clinical protocol with pre-screened patients that adhere to the current indications.

“We monitor the performance of the Nellix System through clinical trials, our complaint monitoring system, physician interaction and available publications,” says Matt Thompson, Chief Medical Officer of Endologix.

“Our independently adjudicated data from the EVAS1 IDE [Investigational Device Exemption] clinical trial indicates that the Nellix System has performed

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well when used consistently with the current indications. However, data from recent Nellix publications leave us concerned that outcomes are suboptimal when the system is used outside current instructions for use.”

To ensure optimal clinical outcomes, the Nellix System will, for the foreseeable future, only be available for use under clinical protocol with pre-screened patients that adhere to the current indications. All cases will be pre-screened by a physician panel and supported by Endologix clinical specialists to ensure adherence to protocol. Compassionate use requests will be reviewed in accordance with the process established by the company and associated national competent authorities.

The existing inventory will be voluntarily recalled. These actions are described in a Field Safety Notification (FSN) issued on 7 January 2019.

“Ensuring patient safety and optimal clinical outcomes is our top priority, and the current level of off-label use of the Nellix System cannot continue if we are to protect and preserve the potential for transformative EndoVascular Aneurysm Sealing (EVAS) therapy,” explains John Onopchenko, Chief Executive Officer of Endologix. “Taking these actions aligns with clinical practice standards, allows us to control off-label use and will help us ensure appropriate application of the therapy.”

This decision is one of several actions taken by Endologix following a new management mandate in August 2018 to ensure the most appropriate use of each of its devices and is in alignment with a recent publication by the European Society for Vascular Surgery (ESVS). Endologix has been in contact with regulatory authorities regarding the Nellix System recall and related matters to help ensure patient safety and continued appropriate access to the Nellix System.

Endologix refined the technical procedure of EVAS and delivered clinical practice updates and advisories regarding use of the Nellix System through a series of FSNs developed in collaboration with regulatory authorities worldwide.

Nevertheless, Endologix has determined that off-label use is occurring at an unacceptable level, with the consequence of sub-optimal results. The company is taking action to ensure optimal outcomes for patients, a press release states.

EVAS therapy was designed to overcome the durability issues of conventional EndoVascular Aneurysm Repair (EVAR) that have led to high rates of aneurysm related mortality when compared with surgical interventions.

“When used as indicated, EVAS is associated with low rates of aneurysm sac growth, Type 2 endoleaks and all-cause mortality,” says Onopchenko. “Our actions are intended to preserve and advance this therapy. Clinical data drives

our decision making and is our basis for competing in the marketplace. Limiting the use of the Nellix System to only those cases rigorously adjudicated by a review board and performed under clinical protocol will ensure that high integrity data is generated and will enable us to deliver on the promise of this potentially disruptive therapy.”

two technologies together.”

“Accurately planning these cases using current technology and manual planning is challenging, time consuming and fraught with error,” stated Tom Douthitt, CEO of Aortica. “Consequently, surgeons tend to shy away from Fenestrated EVAR. By automating case planning to provide an accurate graft plan and coupling that with an

Valiant Navion

FDA approves Valiant NAVION for inclusion in physiciansponsored IDE

The Valiant NAVION stent graft system (Medtronic) has been approved by the US Food and Drug Administration (FDA) for inclusion in a physician-sponsored investigational device exemption (IDE) study.

The physician-sponsored IDE study is currently ongoing at the University of Washington (UW; Seattle, USA) sponsored by the principal investigator and chief of Vascular Surgery, Benjamin Starnes. The FDA decision will allow the use of Medtronic’s Valiant NAVION stent graft system as a platform for fenestrated endovascular aneurysm repair (FEVAR). Together with the AortaFit (Aortica) automated case planning software, NAVION will be evaluated for use in the treatment of complex juxtarenal abdominal aortic aneurysms (AAA). NAVION was recently approved

by FDA and also given CE mark for minimally invasive repair of lesions in the descending thoracic aorta. Starnes recently reported the successful early results for the AortaFit technology in simplifying treatment of patients with highly complex AAA disease.

“I am excited to bring Medtronic’s NAVION into this study,” stated Starnes.

“The device architecture incorporates many of the features we feel are important to simplifying fenestrated EVAR and addressing many of the issues that have limited physician acceptance of FEVAR in the past. In conjunction with Aortica’s automated graft planning technology, the NAVION provides a combination of mechanical strength with ample available fabric area for placement of fenestrations. I am optimistic about the possibilities created by bringing these

appropriately designed endograft both the upfront planning and the procedure itself are dramatically simplified, and the endograft becomes ‘personalised’ to the individual patient’s anatomy. We believe this simplified, personalised approach will significantly increase the number of patients who are candidates for less invasive and personalised EVAR.”

Vanguard IEP

Contego Medical receives 510(k) clearance for Vanguard IEP system

Contego Medical has announced that the US Food and Drug Administration (FDA) has granted 510(k) clearance for its Vanguard IEP Peripheral Balloon Angioplasty System with Integrated Embolic Protection. Contego Medical is a medical device company developing and commercialising a suite of nextgeneration devices that address unmet needs in neurovascular, coronary and peripheral vascular disease.

The Vanguard IEP System uniquely incorporates a peripheral angioplasty balloon and distal embolic filter on the same catheter. The system protects the lower limbs during angioplasty without the need for additional devices or exchanges. The Vanguard IEP System has an over-the-wire design with a sheathless integrated 150-micron pore filter distal to the angioplasty balloon. Contego Medical’s filter is the first to feature in-vivo adjustability to suit varying

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technologies to health care professionals across Australia, and we are pleased to add CGuard EPS to our portfolio of the most innovative stent products available on the market today.”

Product News vessel sizes and maximise capture efficiency. Vanguard IEP was evaluated in the ENTRAP 112-patient post-market registry in Europe in which 100% of patients met primary safety and efficacy endpoints at discharge and 30 days.

“The Vanguard IEP System is designed to protect patients at high risk for embolisation during peripheral angioplasty, such as those with acute limb ischaemia, severe calcification, and chronic total occlusions if crossed intraluminally. It is also well suited to protect patients at high risk for complications should embolisation occur, such as those with poor distal run-off,” said Professor Thomas Zeller, director of the Department of Angiology at Unversitaets Herzzentrum, Freiburg in Bad-Krozingen, Germany and principal investigator of the ENTRAP Study. “In our experience, the device has performed exactly as intended and we are impressed with the ease of use of the system, with no more exchanges required than in a typical angioplasty procedure.”

“Securing FDA clearance for Vanguard IEP represents a major milestone for Contego Medical,” said Ravish Sachar, founder and CEO of Contego Medical. “As the patient population with peripheral arterial disease continues to expand and become more complex, we believe our technology will play a critical role in protecting vulnerable patients from embolic events and thus improve procedural outcomes.” Contego Medical now has two FDA cleared devices dedicated to improving the safety profile and outcomes of interventional procedures.

The Vanguard IEP Peripheral Balloon Angioplasty System with Integrated Embolic Protection is indicated for percutaneous transluminal angioplasty (PTA) and capture and removal of embolic material during angioplasty, for the femoral, iliac, popliteal and profunda arteries. The system is not intended for use in the renal, cerebral, coronary or carotid vasculature.

INCRAFT AAA Stent Graft System receives FDA approval Cordis has announced that the US Food and Drug Administration (FDA) has approved its INCRAFT AAA Stent Graft System for use in complex access anatomies. The INCRAFT system is an ultra-low profile and flexible endovascular aneurysm repair (EVAR) system designed to treat infrarenal abdominal aortic aneurysms (AAA).

The system was given a favorable recommendation on 12 June by a Circulatory System Devices Panel of the Medical Devices Advisory Committee, following a review of clinical data from the pivotal INSPIRATION trial, a prospective, multicentre, single-arm study designed to evaluate the safety and effectiveness of the system in patients with AAA. The trial showed that

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INCRAFT met the primary safety and effectiveness endpoints, with a low rate of major adverse events at 30 days, high rates of successful aneurysm treatment and survival, and no aneurysm ruptures through four years of follow-up.

“We welcome the recent FDA approval of the INCRAFT stent graft system which offers US physicians a treatment option for patients with AAAs who otherwise might not be suitable for other EVAR devices,” said Michel Makaroun, professor and chair of vascular surgery at the University of Pittsburgh Medical Center, and co-principal investigator of the INSPIRATION study. “While EVAR systems have advanced rapidly over the years, there still remains a need for a low-profile EVAR device that is designed to be easy to deliver in complex access anatomies while facilitating precise placement.”

“INCRAFT is an attractive new ultralow profile EVAR option that allows for bilateral in-situ adjustment during the procedure, helping to minimise the need for additional components or extensions,” said Takao Ohki, chairman and professor of Surgery and chief of Vascular Surgery at the Jikei University School of Medicine in Tokyo, Japan and co-principal investigator of the INSPIRATION study.

While several EVAR devices are currently available in the USA, treatment options are limited for many AAA patients with small femoral or iliac arteries or with heavily calcified or tortuous vessels that could lead to complications during the introduction of EVAR devices.

Regulatory and reimbursement approval of CGuard Embolic Prevention System in Australia It has been announced that the CGuard Embolic Prevention System (InspireMD) has been granted regulatory approval by the Therapeutic Goods Administration (part of the Australian Government’s Department of Health) for commercial sale and reimbursement in Australia.

The launch of the CGuard Embolic Prevention System (EPS) will commence immediately in collaboration with InspireMD’s local distributor partner, Diverse Devices, of Sydney, Australia.

“Australia’s Therapeutic Goods Administration sets a high bar in terms of regulatory and reimbursement approval of new medical devices. We believe our approval reflects not only the agency’s recognition of CGuard’s differentiating features versus conventional carotid stents, but also the need for safer treatments for carotid artery disease.

We are eager to begin offering this novel technology to patients in Australia imminently,” said James Barry, chief executive officer of InspireMD. Aidan McEvoy, director of Diverse Devices, commented, “At Diverse Devices, we strive to bring the latest

Valiant Navion receives CE mark approval

CE mark approval has been granted for the Valiant Navion thoracic stent graft system (Medtronic) for the minimally invasive repair of all lesions of the descending thoracic aorta, including thoracic aortic aneurysms (TAA), blunt traumatic aortic injuries (BTAI), penetrating atherosclerotic ulcers (PAU), intramural hematomas (IMH), and type B aortic dissections (TBAD). This follows the recent US FDA approval of the Valiant Navion system.

“In clinical practice we often see patients with a wide range of thoracic aortic anatomies. For example, TEVAR in females doubles the risk of needing an adjunctive iliac access procedure, which can potentially add risk, time, and cost to the procedure,” says Fabio Verzini, associate professor of Vascular Surgery, University of Turin, Italy and

CGuard

European principal investigator for the Valiant Navion IDE study. “The approval of Valiant Navion gives us the ability to broaden the treatable patient population with thoracic aortic disease, including more female patients and those who were previously considered ineligible for TEVAR with a percutaneous approach.”

Medtronic says that the Valiant Navion system is a lower-profile evolution of the market-leading Valiant Captivia thoracic stent graft system, which has treated more than 100,000 patients globally.

Valiant Navion is built on the design philosophy of the Valiant Captivia system for improved performance and increased patient applicability. The system also features the CoveredSeal (proximal covered) and FreeFlo (proximal bare metal) stent configurations—both with tip-capture accuracy, providing physicians with two graft options to treat varying patient anatomies and pathologies.

Approval was based on 30-day primary endpoint analysis of 87 patients consecutively enrolled in the international, multicentre, prospective investigational device exemption (IDE) study analysing the safety and efficacy of Valiant Navion in patients with TAA and PAU. The results demonstrated efficacy in both FreeFlo and CoveredSeal configurations, with no instances of access or deployment failures at implant in the full study cohort. Through 30 days, data showed low rates of peri-operative mortality at 2.3% and secondary

procedures at 2.3%. The rate of Type Ia endoleaks was 1.2% at one-month imaging follow-up.

Vivasure Medical announces launch of the PerQseal large bore closure device

Vivasure Medical has announced the European launch of the PerQseal closure device for large-bore transcatheter procedures, including transcatheter aortic valve implantation (TAVI), thoracic endovascular aneurysm repair (TEVAR), and endovascular abdominal aneurysm repair (EVAR)—all of which require large bore femoral artery access.

A press release reports that PerQseal is the first sutureless, fully absorbable synthetic implant for large bore arterial punctures, adding that the PerQseal technology consists of an intravascular patch that seals the vessel from the inside, returning the artery to its natural state.

Horst Sievert (CardioVascular Center, Frankfurt, Germany) says: “Closing the artery has been a concern since we started using transcatheter techniques for valve implantation. The PerQseal device is a very innovative solution for closing large holes, and we are enthusiastic to make it part of our armamentarium.”

Gerard Brett, co-founder and CEO of Vivasure Medical, states: “We are excited that the PerQseal device is now widely available to European physicians, providing a safe and simple option for the closure of large puncture holes that leaves behind no sutures, metal implants, or collagen. This commercial launch is a key milestone for Vivasure as we journey to enable better patient outcomes in fully percutaneous large bore endovascular procedures.”

Humacyte commences phase II vascular trauma trial

Humacyte has announced the initiation of a US phase II vascular trauma clinical trial of Humacyl, its investigational human acellular vessel, for vascular replacement or reconstruction in patients with life- or limb-threatening vascular trauma.

The phase II vascular trauma study was initiated last month and will be conducted at six sites in the USA. The trial will evaluate approximately 40 adult patients with life- or limb-threatening vascular trauma that require surgical repair. Enrolment in the trial has begun and will continue for 24 months. The initial patients were enrolled at Rutgers University Hospital in Newark, USA and R Adams Cowley Shock Trauma Center in Baltimore, USA; other sites expected to enrol patients include Johns Hopkins University in Baltimore, USA; Marcus Trauma Center in Atlanta, USA; Ryder Trauma Center in Miami, USA; and Rocky Mountain Regional Trauma Center in Denver, USA. The first patient in this phase II vascular trauma study was enrolled in the USA in September 2018, and has now surpassed 30 days in the study. Humacyte anticipates top line patient data from this investigative study to be available in late 2020.

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Clinical News TOBA II BTK clinical trial completes enrolment

The Tack Optimised Balloon Angioplasty II below-the-knee (TOBA II BTK) clinical trial has successfully completed enrolment, ahead of schedule. This study, sponsored by Intact Vascular, is the first pivotal trial investigating a permanent vascular implant in arteries below the knee.

The study will examine the safety and efficacy of the Tack endovascular system (Intact Vascular) when used to repair dissections in the arteries below the knee following percutaneous transluminal angioplasty as a treatment for critical limb ischaemia (CLI).

“Patients with CLI experience painful symptoms and are at increased risk of amputation. Unfortunately, therapeutic options are very limited, and no scaffolding solutions are currently FDA-approved for BTK interventions,” commented George Adams, director of Cardiovascular and Peripheral Vascular Research, UNC Rex Hospital, Raleigh, USA, and co-principal investigator for the TOBA II BTK study. “The potential to have a treatment option that maintains vessel integrity and improves blood flow will have a significant clinical impact for treating patients with below-the-knee disease.”

With enrolment completed at 41 US and European sites, the TOBA II BTK trial is a single arm, prospective study to investigate the safety and efficacy of the Tack endovascular system for the repair of post-angioplasty dissections in the mid/distal popliteal, tibial and peroneal arteries. All 233 patients enrolled suffered from CLI, underwent standard balloon angioplasty, and consequently experienced at least one dissection requiring repair.

“Dissections are an expected consequence from balloon angioplasty, yet can have significant implications for patients,” states Patrick Geraghty, professor of Surgery and Radiology at the Washington University School of Medicine in St Louis, USA and coprincipal investigator for the TOBA II BTK trial. “Early results with the Tack implant are promising, and I look forward to integrating this technology into my below-the-knee treatment algorithm.”

“Reaching full enrolment for our TOBA II BTK study is an important milestone for below-the-knee interventions,” comments Peter Schneider, a vascular surgeon, and cofounder and Chief Medical Officer of Intact Vascular. “As the first dissection repair device purpose-built for use in these small vessels, we are excited to provide a solution for patients suffering the painful and debilitating effects of CLI and who currently do not have adequate treatment options available. The Tack implant is a novel adjunct therapy that should diminish the chance that these patients will require an amputation.”

The Tack endovascular system is designed to be used in conjunction with peripheral balloon angioplasty in the treatment of peripheral arterial disease. The system is pre-loaded with six self-expanding nitinol devices for above-the-knee interventions, or four for below-the-knee, and can be deployed to treat multiple dissections using a single catheter.

Intact Vascular is sponsoring three clinical trials to evaluate its Tack endovascular system: TOBA II, TOBA II BTK and TOBA III. TOBA II is investigating the combination of the Tack implant with plain angioplasty balloons and the BD Lutonix DCB in arteries above the knee, and successfully achieved both primary and secondary endpoints, as reported at VIVA (5–8 November, Las Vegas). TOBA II BTK is investigating the combination of the Tack implant with plain balloon angioplasty in the arteries below the knee. TOBA III has completed enrolment in Europe and is investigating the combination of the Tack implant with the Medtronic IN.PACT Admiral DCB, inclusive of long lesions.

The original TOBA BTK study in 2016 reported positive six-month results, with a primary patency at that time-point of 87.1%.

First patients treated in United States with OrbusNeich Teleport Microcatheter

The first patients in the United States have been treated using the OrbusNeich Teleport Microcatheter (Teleport; Cardiovascular Systems), which recently received US Food and Drug Administration (FDA) 510(k) clearance.

Teleport is a microcatheter designed for deliverability and support, with a tip designed to enable access in the most challenging lesions.

Annapoorna S Kini, director of the Cardiac Catheterization Laboratory at Mount Sinai Medical Center, New York, USA, and Emmanouil Brilakis, interventional cardiologist at Minneapolis Heart Institute at Abbott Northwestern Hospital, Minneapolis, USA, treated the first patients in the United States with Teleport.

Kini said, “I am excited and honoured to be the first to use Teleport microcatheter in the United States.

Teleport allowed me to deliver the microcatheter easily through tortuous coronary vasculature while maintaining catheter position for guidewire exchange treating a complex chronic total occlusion.”

Brilakis added, “I had the opportunity to use the Teleport Microcatheter in Europe and was impressed by its balance of deliverability and support. Teleport’s robust tip design is unique, enabling access to tight lesions while providing the torqueability necessary to treat very challenging lesions. I’m excited to have this device available to treat my patients

here in the United States.”

Scott Ward, CSI’s chairman, president and chief executive officer, said, “We are committed to building a comprehensive cardiovascular company and leveraging our commercial footprint and clinical value to become the partner of choice in the revascularisation of patients with complex peripheral and coronary artery disease.”

Enrolment complete in T.I.N.T.I.N. study

iVascular has announced the completion of enrolment of patients in its T.I.N.T.I.N. (Treatment with the Luminor DCB and the iVolution self-expanding stent) study.

The effectiveness of drug-coated balloons (DCB) to inhibit restenosis in symptomatic superficial femoral artery (SFA) lesions has been proven in many studies. However, the longer and the more complex these lesions are, the more bailout stenting or spot stenting is necessary. Regarding selfexpanding stents, the main advantage is the achievement of maximum arterial lumen gain. Nevertheless, the increase of restenosis in long-term results has been demonstrated in several studies, iVascular states in a press release.

The release adds, “What if we combine both therapies resulting in perfect treatment for complex lesions?

A combination between the properties of Luminor, the DCB with the best outcomes in SFA and popliteal arteries, and the iVolution self-expanding stent, known for its high flexibility and radial force, can be the solution to avoid bailout stenting and restenosis in long-term results.”

The T.I.N.T.I.N. study aims at evaluating the 12-month outcomes of a combination therapy of the Luminor DCB and iVolution stent, in long TASC C and D femoropopliteal lesions. This prospective, multicentre, physicianinitiated study’s primary endpoint is freedom from clinically-driven target lesion revascularisation (TLR) at 12 months. Secondary endpoints are defined as primary patency rate at six- and 12-month follow-up, technical success, freedom from clinically-driven TLR at six-month follow-up, clinical success at follow-up and serious adverse events.

Koen Deloose (AZ Sint Blasius Dendermonde, Belgium), T.I.N.T.I.N. study principal investigator states, “The enrolment has just been completed, and we expect outstanding results from this trial, as both Luminor DCB and iVolution self-expanding stent are products that have proven their safety and efficacy in previous studies.”

The enrolment of 100 patients has been completed and the first outcomes of the study will be presented at LINC 2019.

First European patients treated with Peripheral Orbital atherectomy system The first patients in Germany have been treated with the Stealth 360 Peripheral Orbital Atherectomy System (OAS; Cardiovascular Systems Inc).

The German cases represent the first commercial use of Peripheral OAS in

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Tobias Achenbach, head of the Radiology Department at the St Vincenz Hospital, Cologne, Germany, where the first patients in Germany were treated, says, “CSI’s minimally invasive orbital atherectomy technology allows physicians to gently modify calcified plaque and enables peripheral revascularisation for patients with severely calcified arteries. The introduction of orbital atherectomy in Germany greatly improves the treatment options for my patients suffering from peripheral arterial disease.”

Dierk Scheinert, head of the Department of Medicine, Angiology and Cardiology, Park-Krankenhaus Leipzig, and Head Department of Angiology, University Hospital Leipzig Heart Center, Leipzig, Germany says, “Of those suffering from peripheral arterial disease, many progress to critical limb ischaemia, the most severe and potentially deadly form of peripheral arterial disease. If left untreated, critical limb ischaemia can lead to amputation. The unique ability of orbital atherectomy to safely treat calcified peripheral lesions, both above and below the knee, will allow physicians in Germany to help a very challenging patient population.”

In July 2018, CSI announced that it had signed an exclusive international distribution agreement with OrbusNeich to sell its coronary and peripheral OAS outside of the USA and Japan.

First US patient enrolled in ILLUMENATE BTK study of Stellarex 0.014 DCB

The first US patient has been enrolled in the Stellarex ILLUMENATE belowthe-knee (BTK) investigational device exemption (IDE) study, led by principal investigators Bill Gray and Mahmood K Razavi. This global, prospective, randomised, multicentre trial is designed to assess safety and effectiveness of the Stellarex 0.014 drug-coated balloon (DCB) versus percutaneous transluminal angioplasty (PTA) in patients with critical limb ischaemia (CLI).

The trial will enrol 354 patients at 45 sites in USA, Europe and Australia in the next 12–18 months. The first patient in the USA was enrolled by Craig Walker at the Cardiovascular Institute of the South in Houma, Louisiana, USA. “Several studies have shown the safety and durability benefits of the Stellarex balloon,” says Mahmood K Razavi, St Joseph’s Hospital in Orange, USA and principal investigator of the ILLUMENATE BTK study.

“This study will look at findings that continue to demonstrate the benefits of the Stellarex 0.014 DCB for BTK peripheral arterial disease (PAD) and its safety and durability for patients. Given the challenging chronic nature of BTK PAD, we are hoping to find that through sustained patency using Stellarex, we can improve healing, and reduce target lesion revascularisation and major amputation.”

The Stellarex 0.014” OTW drugcoated balloon is designed to restore and maintain blood flow to arteries in patients with peripheral arterial disease.

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Industry News Unique therapeutic approach to treating uncontrolled hypertension receives US$77 million financing

Ablative Solutions has announced the first close of its US$77 million Series D funding round. The round was led by new investor Glide Healthcare, and co-led by exiting investor BioStar Ventures, as well as an undisclosed new strategic corporate investor. Existing investors, including Michigan Accelerator Fund, Novus Biotechnology, and other individual investors, also participated in the Series D funding round.

Funds from the round will be used to complete clinical trials in support of US and European regulatory submissions for the company’s minimally invasive renal denervation technology designed to help reduce blood pressure for people with uncontrolled hypertension, while taking antihypertensive medication.

“BioStar Ventures focuses on transformational health care investments, and we believe Ablative Solutions fits that model perfectly,” says Michael Fulton, senior managing director of BioStar Ventures, an investor in the company since its Series A round in 2012.

Ablative Solutions’ alcohol-mediated renal denervation procedure is performed using the investigational Peregrine system kit, which is engineered to target nerves known to influence the body’s regulation of blood pressure. The Peregrine kit delivers dehydrated alcohol in small doses directly to the space outside of the renal artery to block the overactive signalling of the sympathetic nerves.

“Hypertension creates a significant burden on the healthcare system, increasing the risk of serious cardiovascular events and stroke,” comments Gilde Healthcare’s Geoff Pardo. “We see tremendous potential for Ablative Solutions’ approach and believe the team has a solid plan for building the clinical data through the TARGET BP clinical programme.”

Ablative Solutions’ CEO and CMO Tim Fischell enthuses: “We are excited to have the support of this thoughtful and high-powered group of investors, which will allow the company to complete the studies required to seek regulatory approvals in Europe and in the USA.”

Merit Medical acquires assets of Vascular Insights

Merit Medical Systems, Inc. has announced that it has acquired substantially all of the assets of Vascular Insights, LLC, based in Quincy, USA. Vascular Insights’ primary assets are the ClariVein IC and ClariVein OC specialty infusion and occlusion catheter systems, which have been utilised in more than 120,000 cases to treat superficial venous disease, particularly below the knee (BTK), and in venous leg ulcers (VLU).

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The ClariVein systems address a $700 million global market. The ClariVein IC system has 510(k) clearance from the US FDA, the ClariVein OC system is CEmarked, and the systems are covered by 43 patents issued worldwide.

The purchase price was US$40 million plus additional milestone payments that could amount to an additional US$20 million if certain sales targets are achieved.

“We have had our eye on these products for some time,” said Fred P Lampropoulos, Merit’s chairman and CEO. “These products complement our existing peripheral intervention sales platform, add to our capability to provide many existing Merit products, such as our micropuncture and vascular access products, and increase our ability to customise the entire procedure for our customers. Additionally, our global sales footprint allows for expansion of sales in previously underserved areas.”

“We are excited to reach this agreement with Merit,” said James (Chip) Draper, chief executive officer of Vascular Insights. “This acquisition will allow ClariVein to reach more patients in more ways and in more places with the commitment to treat venous disease.”

“I am thrilled that Merit and ClariVein will bring transformative relief to millions of venous disease sufferers worldwide, especially those suffering from debilitating venous leg ulcers,” said Michael Tal, inventor of the ClariVein systems and co-founder of Vascular Insights.

The effect of the Vascular Insights acquisition on Merit’s earnings for 2018 is expected to be dilutive to Merit’s earnings per share on a GAAP basis of approximately (US$0.03) per common share and on a non-GAAP basis of approximately (US$0.02) per common share, with both Merit’s GAAP, non-GAAP gross margins, and revenue contributions expected to be inconsequential for 2018.

Otsuka Medical Devices completes aquisition of Veryan Medical Otsuka Medical Devices, a 100% subsidiary of Otsuka Holdings Co., Ltd., and Veryan Medical have announced the completion of the acquisition of Veryan

by Otsuka Medical Devices through its UK subsidiary Otsuka Medical Devices UK Ltd. Veryan’s BioMimics 3D peripheral vascular stent received approval from the US Food and Drug Administration (FDA) in October 2018. Following the acquisition, Veryan and Otsuka Medical Devices plan to collaborate in developing Swirling Flow stents for use in the treatment of vascular disease. As part of the acquisition, Veryan’s operations in Galway, Ireland, will be retained by Otsuka Medical Devices and will play a key role in the continued development of

the Swirling Flow technology.

Chas Taylor, CEO of Veryan, said: “We are delighted to become part of Otsuka Medical Devices. This will allow Veryan to build on the strong clinical data with the BioMimics stent and realise the potential to significantly advance the treatment of peripheral vascular disease.”

Noriko Tojo, CEO of Otsuka Medical Devices commented: “Veryan’s stent technology represents an excellent fit with our existing activities and has considerable future development potential.”

Otsuka Medical Devices Co., Ltd. focuses on the development and commercialisation of endovascular devices that provide new therapeutic options in areas where patient needs cannot be met through pharmaceutical or other conventional treatment.

Abiomed invests $15 million in Shockwave Medical A press release reports that Abiomed is to invest US$15 million in Shockwave Medical and the two companies will collaborate on a training and education programme in the USA and Germany focused on the benefits of complementary use of their respective technologies.

The press release states that Shockwave’s intravascular lithotripsy (IVL) technology employs sonic pressure waves to safely crack vascular calcium within the vessel wall, which enables arteries to expand under low pressure and become more compliant.

It adds that Shockwave markets its Shockwave M5 Peripheral Intravascular Lithotripsy Catheter in the USA and Europe, but notes that the Shockwave M5 catheter is increasingly being used in patients with heavily calcified Iliac arteries in order to facilitate the transfemoral delivery of sophisticated devices with catheters, including transcatheter aortic valve implantation (TAVI) and Abiomed’s Impella. IVL enables this patient group to benefit from these life-saving therapies when they would otherwise be ineligible for the procedure or would be at increased risk for procedural complications. In Europe, Shockwave also markets its coronary catheter—Shockwave C2— which is used to treat severely calcified de novo coronary artery disease.

Doug Godshall, president and CEO of Shockwave Medical, states: “While we are still early in our commercial scaling both in the US and Europe, I am pleased with how positively our Shockwave technology has been received and how many different types of patients and vessels our customers are able to safely treat with our IVL system. We are delighted to be able offer patients our solution in combination with Abiomed’s Impella technology using a minimally invasive approach, which should meaningfully improve outcomes.

With Abiomed’s best-in-class approach to training and education, Shockwave will be able to more efficiently increase awareness and introduce IVL to customers, which we believe will help

them better treat their most challenging patients. We are encouraged to see the positive clinical response we have witnessed to date.”

Boston Scientific announces recommended offer to acquire BTG

Boston Scientific has announced it has reached an agreement on the terms of a recommended offer to acquire BTG, a company headquartered in the United Kingdom, which develops and commercialises products used in minimally-invasive procedures targeting cancer and vascular diseases, as well as acute care pharmaceuticals.

The transaction has been unanimously approved by the boards of directors of Boston Scientific and BTG. Under the terms of the transaction, holders of BTG’s common shares would receive cash consideration of 840 pence per share. The total cash consideration for 100% of BTG’s equity is approximately £3.3 billion, or U.S.$4.2 billion. The transaction is intended to be effected by way of an English court-sanctioned scheme of arrangement, and is expected to close in the first half of 2019, subject to receipt of required regulatory approvals and the approval of BTG’s shareholders and the UK court.

BTG has three key businesses, the largest of which is its Interventional Medicine portfolio, which encompasses several peripheral interventional product lines. The interventional oncology franchise includes the TheraSphere Y-90 radiotherapy microspheres and the GALIL cryoablation system, used to treat patients with liver, kidney and other cancers. More than 840,000 people are expected to be diagnosed with liver cancer in 2018, and that number is expected to grow to 1.1 million by 2030. Kidney cancer is among the 10 most common cancers in both men and women.

The company’s Interventional Medicine business also has a highlydifferentiated vascular portfolio, including filters, crossing catheters, microfoam and the EKOS Endovascular System. The EKOS system, in combination with clot-dissolving drugs, breaks down blood clots to restore blood flow in patients with pulmonary emboli, deep vein thrombosis and peripheral arterial occlusions, and was the first device cleared by the Food and Drug Administration for the treatment of pulmonary embolism.

Boston Scientific has received irrevocable undertakings to vote in favour of the transaction from BTG’s three largest shareholders, covering an aggregate of approximately 33% of BTG’s outstanding shares, as well as from all of BTG’s directors, who hold an additional 0.3% of BTG shares.

The transaction would be funded with a combination of cash on hand and proceeds from debt financing entered into by Boston Scientific.

The transaction is expected to be two to three cents accretive to Boston Scientific adjusted earnings per share in 2019, and increasingly accretive

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thereafter. On a GAAP basis, the transaction is expected to be dilutive in 2019, and less dilutive or increasingly accretive thereafter, as the case may be, due to amortisation expense and acquisition-related net charges.

Endologix announces public offering of common stock

Endologix has announced that it has commenced a registered underwritten public offering of US$20 million of its shares of common stock. In addition, Endologix has granted the underwriter a 30-day option to purchase up to an additional US$3 million of its shares of common stock. All of the shares in the offering are to be sold by Endologix.

BTIG, LLC is acting as sole book-running manager for the offering.

Endologix intends to use the net proceeds from this offering to redeem all of its US$18.3 million 2.25% Convertible Senior Notes due 2018 and to pay related fees, costs, expenses and other related payments, and the remaining proceeds, if any, for working capital and

general corporate purposes.

A shelf registration statement on Form S-3 relating to the public offering of the shares of common stock described above was filed with the Securities and Exchange Commission (the SEC) and became effective on 3 August, 2018. A press release advises that before you invest, you should read the prospectus in the registration statement and related preliminary prospectus supplement that Endologix will file with the SEC for more complete information about Endologix and this offering.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

Terumo Aortic acquires Serom Medical Technology

Terumo Aortic has announced the acquisition of Serom

Medical Technology S.r.l. by Vascutek Ltd and the subsequent merger with Bolton Medical S.r.l. in Italy.

Serom Medical Technology S.r.l. has successfully represented Vascutek in Italy for more than 30 years and a close partnership has been forged between the two companies over this long period of time. Aligned with this acquisition, Bolton Medical in Italy and Serom Medical Technology will merge and trade under the brand Terumo Aortic located in Rome.

A press release states that Terumo Aortic’s vision is to provide the most comprehensive portfolio of endovascular, surgical and hybrid products with an outstanding level of customer service.

Paul Holbrook, president and CEO Terumo Aortic, says: “This acquisition represents an important milestone as we continue to grow our business globally and become a world leader in driving innovation and developing devices to treat aortic disease. We very much look forward to further developing our strong relationships with clinicians in Italy and strengthening our collaboration with clinicians supported by our new combined team.”

Calendar of events 22–25 January

15–17 February

LINC: Leipzig Interventional Course Leipzig, Germany W linc2019.com

American Society of Diagnostic and Interventional Nephrology: ASDIN Atlanta, USA W asdin.org

7–9 February

CACVS: Controversies and Updates in Vascular Surgery Paris, France W cacvs.org

3–7 March

13–15 February

12–13 March

EVC: European Vascular Course Maastricht, the Netherlands W vascular-course.com

3rd Maastricht Consensus Conference on Thrombosis Maastricht, The Netherlands W mcct.eu 15–17 February

American Society of Diagnostic and Interventional Nephrology: ASDIN Atlanta, USA W asdin.org

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– poll (EVAR), but portion 30-day Yes the proximal group and . A CX audience ference in into the distal extended into lar strategy nearly 80% significant 9% revealed that the endovascu group and subgroup artery, and results of the session 94.4% primary a the 12-month the open repair a strong benefit for d them liteal artery”. and showed a agreed that encourage showed results months, E trial in women analysis at nine The trial lar strategy the IMPROV often. rate at the with Eluvia the characterarisation 2 EVAR more the endovascu men. patency rate on page at baseline, to perform similar with Continued lesion revascul the fact that Imperial College,data compared groups were 3.6% target Janet Powell, the latest of the two in each istics ters presented ual patient e manthree-quar London, UK, (Immediat with almost aneurysms Pooled individ men. “The from the IMPROVE with rupture: large with outcomesthe 12-month group being the patient trial that were also very group being data agement of presented lar repair) in this trial the Balm each in from Ron endovascu Open vs. meta-analysis outcomes followprincipal average diameters outcomes from the she said. The and reported one-year of endovascular patient data over 8cm,” trials of strategy was mortality individual d controlled AJAX of ruptured ing either a one-year outcome were reinterven randomise or open repair The s; the Dutch ted three outcomes repair first health-rela secondary aortic aneurysm. ruptured aneurysm 2013), the discharge, benefit abdominal of Surgery tions, hospital costs, quality-adjustedte no survival trial (Annals trial (EJVES 2015) life, results demonstra lar strategy for rupquality-ofiveness.

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E cost-effect and for the endovascuat one year. However, that IMPROV life-years were and the UK Powell noted the for the all trials that tured aneurysm At CX 2015, answer lar-first strategy “These were with a clinical designed to an endovascu ruptured aneurysms on patients In the trial was with a patient nt of performed aneurysm. what to do room manageme discharge of ruptured question of mortality patients faster and it is suspicion to the emergency does offer abdomitrial the 30-day ately who presents quality of life the AJAX of ruptured factors was approxim with better with a diagnosis . “What we had ive. Both these in both groups it was 22% and in also cost-effect patient and clinical an endonal aortic aneurysm for 25%, in ECAR a slightly was that using it was heard. are necessary which had anticipated aking, delegates in April in wherever IMPROVE, design, it was 35% decision-m vascular strategy, feasible, we could were published (EHJ). different study(BMJ 2014), but all These data of morphologically Heart Journal in each group operative mortality to lsbeck te the benefit the European a pragmatic, multicenreduce 30-day open repair group , Stefan Müller-Hü failed to demonstra setting. “The trial ranin the IMPROVE emergent from 47% lar repair was and one Canada)a clinical EVAR in the by the fact endovascu tre (29 UK 33% where were hampered so much patients with she said. results 613 y,” 316 domised repair performed on page 2 used extensivel “At one year, ruptured aneurysm, stratthat open Continued diagnosis of lar-first Powell added: was 41.1% for VN App an endovascu was suitable patients to y group and all-cause mortality hing morpholog lar strategy egy (if aortic if not) and 297 to open @VN_publis the endovascu and open repair drew attention to also ews repair. Powell m/VascularN

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VascularNew

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15–18 April

23–24 May

26–27 April

12–15 June

Charing Cross Symposium London, UK W cxsymposium.com 27th Annual Pennsylvania Hospital Vascular Symposium Philadelphia, USA W vascularmeeting.com

Aortic Summit 2019 Lugano, Switzerland W aorticassociation.org SVS Vascular Annual Meetings National Harbor, Maryland, USA W vascular.org 27–28 June

LINC Asia-Pacific Hong Kong W linc-around-the-world.com

Paris Endovascular Aortic Course Le Plessis-Robinson, France W peacworkshop.com

BSET: British Society of Endovascular Therapy annual meeting Wotton-under-Edge, UK W bset.co.uk

27–29 March

22–25 May

15–19 August

11–12 April

23–24 May

23–27 August

SITE: International Symposium of Endovascular Therapeutics Barcelona, Spain W sitesymposium.com 11th Congress of the Vascular Access Society Rotterdam, The Netherlands W vas2019.com

13–18 May

8th International Symposium on the Diabetic Foot The Hague, the Netherlands W diabeticfoot.nl Critical Issues in Aortic Endografting Liverpool, UK W critical-issues-congress.com

ANZSVS Annual Scientific Meeting 2019 Adelaide, Australia W anzsvs.org.au ESVS: European Society for Vascular Surgery annual meeting Hamburg, Germany W esvs.org

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