Venous News 7 — September Issue

Sept

18

“Crystal clear” evidence that higher compression reduces ulcer recurrence

Issue

7

Athanasios Giannoukas:

Managing superficial vein thrombosis Page 12

A randomised study in Serbia has found that the use of higher pressure compression stockings is associated with a lower rate of venous leg ulcer recurrence over a fiveyear period. Speaking at the European Venous Forum annual meeting (EVF; 28–30 June, Athens, Greece), Dragan Milic, Medical Center of Nis, Serbia, said that for efficient long-term prevention of ulcer recurrence, the results of his study are “crystal clear”—the stronger the compression, the better the results.

Kathleen Gibson:

Profile

Page 10

New intravascular ultrasound-based scoring system may predict future stent failure

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ilic upheld compression therapy as a “cornerstone” of venous disease treatment, which he argued should be the focus of all venous specialists, including surgeons. In a bid to recentralise the debate around this treatment, rather than interventional or pharmacological therapy, Milic reaffirmed his view that “good compression is the foundation of care”.

Venous insufficiency and venous ulcerations are an important social and healthcare problem, with an overall incidence of venous ulcers in patients older than 45 years of 3.5 per 1,000 every year.

Milic explained that, according to the Bohn Vein study, 0.1% of the adult population has an active venous ulcer and 0.6% has a healed venous ulcer.

Further, 1.5% of European adults will suffer a

Dragan Milic

venous ulcer at some point in their lives and the incidence of chronic venous insufficiency according to many studies is 0.5–3% in adults, and 70% of people with venous leg ulcers experience negative emotional impact. Finally, the treatment of venous leg ulcers is very expensive, and accounts for 1% of the healthcare budget, with annual healthcare costs for venous ulcers estimated at £300 million in the UK, €250 million in Germany and US$1 billion in the USA. Milic further reported that while there is no firm data for the Balkan region in Eastern Europe, it is believed that the cumulative prevalence of chronic venous insufficiency and venous ulceration is much higher than 1% and that in Serbia alone, 40,000 were reported as having an active venous Continued on page 2

To accompany the growing importance of intravascular ultrasound (IVUS) as an adjuvant diagnostic tool when treating deep venous disease, a study sought to create an IVUS-based scoring system able to predict stent failure in the treatment of May-Thurner Syndrome.

The findings were revealed at the Society for Vascular Surgery Vascular Annual Meeting (VAM; 20–23 June, Boston, USA) by Steven D Abramowitz, MedStar Washington Hospital Center, Washington DC, USA.

T

he prediction of stent failure qualifies a step forward in both standardising and comparing outcomes for endovascular venous treatment. In turn, the investigators suggest the use of the IVUS scoring system allows for the objective characterisation of iliac vein lesions, and may be able to predict lesions at high risk of reintervention.

The study took place within two collaborative institutions, analysing 118 patients diagnosed with May-Thurner syndrome, all of whom underwent IVUS-guided stent placement from April 2009 to May 2015. Patients included 86 (73%) females and 32 (27%) males with a mean age of 46 years (range: 17–83 years). All patients had C3–6 Continued on page 4

2

June

18

Venous leg ulcers

Issue

7

“Crystal clear” evidence that higher compression reduces ulcer recurrence Continued from page 1

ulcer 10 years ago.

The current recommendations for the treatment of chronic venous disease and venous ulcers are: correction of the underlying venous lesion (reflux, obstruction); lower limb compression/ ambulation; pharmacologic therapy; and skin grafting or tissue bioengineering.

“The EVRA study says that every correction of the underlying venous disorder will lead to faster healing time and longer ulcer free time.

But, we must acknowledge that this study included only the patients who had small venous ulcers for a short duration—they only included patients who had a venous ulcer from six weeks to six months,” Milic pointed out.

He added that ultimately, it is well established that good compression is the foundation of care. “Compression therapy is the cornerstone of venous treatment. It is the most widely-used treatment for venous leg ulcers, with published healing rates varying widely from 40–90%, and recurrence rates ranging from 25–70%. It is believed that the application of external pressure to the calf muscle raises the interstitial pressure, resulting in improved venous return and reduction in venous hypertension.”

In the reported study, Milic and colleagues sought to establish the efficacy of two different strengths of compression hosiery (Class 2 and Class 3) in the prevention of venous leg ulcer recurrences. It was an open, randomised, single centre study, with a five-year follow-up.

Three hundred and eight patients with recently healed venous leg ulcers and corrected underlying venous disease were included in the study and randomised into two groups. Group A received Class 3 compression, where the compression system consisted of a heelless open-toed elastic compression device knitted in tubular form (Tubulcus, Laboratories Innothera); and

Group B received Class 2 compression with an elastic stocking (Rudo).

Patients were instructed to wear compression stockings during the first two years of the follow-up period during the day and night. In the third, fourth and fifth year of follow-up, patients were instructed to wear elastic stockings only during the day. One pair of elastic stockings was changed every four months.

The main outcome measures were recurrence of leg ulceration and compliance with treatment. Further, Milic noted, this study is the only one of its kind to also measure the subbandage or interface pressure (using the Kikuhime device, TT MediTrade).

Giving the study results, Milic reported that the two groups were well matched for sex, age and history of venous disease. The most interesting aspect of the patient characteristics, he noted, are the size and duration of the ulcers. All the patients who were primarily treated for venous ulcers had very large ulcers of long duration, he said, hypothesising that this group of patients will be more likely to have a recurrence than the patients who had a small venous ulcer of shorter duration— like those enrolled in other trials.

Twenty eight patients did not comply with their randomised compression class, 18 (11.39%) in Class 3 and 10 (6.66%) in Class 2 (p<0.05). Overall, 47.72% (147/308) of patients had recurrent leg ulceration by five years.

Recurrence occurred in 51 (32.27%) of 158 patients in the Class 3 elastic compression group and in 96 (64%) of 150 patients in the Class 2 compression group (p<0.05).

Based on the measurement of interface pressure below the stockings, the study results show a difference of more than 10mmHg between the two types of stockings used. Group A patients, who received Class 3 stockings, had a median pressure measurement of 30.7mmHg

in the supine position, compared to a median measurement of 19.4mmHg in the Class 2 stocking group; and a median pressure measurement of 33.7mmHg in the standing position, compared to 20.7mmHg in the Class 2 group.

Further, Milic maintained, “if you look at all the parameters, you will find that only Class 2 compression was linked to the emergence of the recurrences—previous operations, previous DVTs, the female gender, body mass index, and so on, did not have any significance of the emergence of the venous leg ulcer recurrences, only Class 2 compression.”

In conclusion, Milic stated that the results obtained in this study suggest that Class 3 compression stockings provide statistically significant lower ulcer recurrence rates compared to Class 2 compression stockings.

“Although we do not have any evidence so far, it may be prudent to advise patients to wear a lower class of compression stocking during the night and to wear elastic stockings of higher compression during the day,” he added.

Responding to audience discussion relating to patient compliance with compression—especially the higher pressure compression he is suggesting—he said, “This problem of compliance and non-compliance is far more pronounced in the initial phase when we treat the venous ulcers, it is much less pronounced in the maintenance phase. In our primary study [where these patients were initially treated for their leg

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ulcers], we included patients with very large ulcers of long duration, and when we started treating them with the high pressure compression system, then we had a harder time convincing them to comply with the treatment. But that was only for the first month; after that, the patients adjusted to the high pressure compression.”

As for this study’s variation from standard practice, Milic maintained that the results of the study are “crystal clear”, adding that “for healing, you have to treat only the wound… no antibiotics, no fancy dressing, only simple dressing with compression treatment does the trick… The main thing, if we want to have sound evidence, is to measure the pressure.

As far as I know, this is the only study that really measured the pressure below the stockings. All the other studies that are published found no difference between Class 1 and Class 3 compression, but the pressure interface is not recorded. But here in this study, we have the results—the stronger the compression, definitely the better results; it is a crystal clear conclusion.”

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4

Sept

18

Venous stenting

Issue

7

New intravascular ultrasound-based scoring system may predict future stent failure Continued from page 1

venous disease, a life expectancy of over five years, and were ambulatory.

Each patient was treated in a similar fashion, with ascending venography performed on both patient’s presenting with either C3–C6 disease, or acute DVT undergoing thrombolysis. Lesions were first treated, identified, then assessed at a post-operative window of six, 12 or 24 months. If the patient was found to have a stenosis on venous duplex, they either went for a CT venogram or ascending venogram, to confirm the presence of a new lesion.

An IVUS-driven scoring system was generated, containing seven categories for assessment. The first—and only category that allows for a three-point scoring system—was lesion presentation (nonthrombotic, acute, or chronic), followed by type of May-Thurner lesion (non-occlusive or occlusive).

The IVUS-driven categories consisted of: venous disease length (<180mm or >181mm), venous inflow compliance (presence or absence of respiratory variation) and iliocaval confluence disease involvement (present or absent). Lastly, iliocaval confluence stenting obligation (stented or spared) and presence of perivenous collaterals before and after stenting (non or resolved), were assessed and scored.

Other than the first (scored 0, 1 or 2), the remaining six categories were scored 0 or 1, tabulated for each patient at the time of initial intervention.

Of all 118 patients that underwent treatment, 38 (32%) developed moderate (>50%) in-stent stenosis, required thrombolysis, or underwent additional stenting procedures, and hence were considered treatment failures. According to the investigators, there is a lack of predictability in future outcomes for asymptomatic patients with occlusions, which meant their identification of a treatment failure in

Steven D Abramowitz

this case was very broad.

Eighty (68%) patients required no additional interventions and were considered treatment successes. The overall mean IVUS score for the entire patient population was 5.22 (±1.40). The mean IVUS score in the treatment failure cohort was 5.64 (±1.20) compared with a score of 4.67 (±1.47) in the treatment success group (p=0.0081).

When breaking down the results, Abramowitz suggested that no one category was responsible for a statistically significant difference in the outcome of the patients. Instead, a significant breaking point

for the patients that had a composite score of greater than 5 was found. For example, if a patient had a composite score greater than 4, relative risk of stent failure after two years was 1.6. However, a score of 5 would mean this relative risk at two years jumps to 2.4.

A multivariate analysis allowed the investigators to determine if this risk was associated with confounding factors, such as: age, gender or race.

Yet, they found no statistically significant difference in terms of the outcome of the patients. Additionally, they looked at both presentation of disease (C3–C6 disease) and the patients’ underlying anticoagulant conditions. Again, these variables were not found to correlate with any statistical difference in outcome over the course period.

Due to the multi-factorial nature of stent-failure, Abramowitz concluded that the IVUS-based scoring system may have a role in predicting it, as higher composite scores were associated with increased stent failure, as well as an increased relative risk of it occurring. Therefore, a scoring system that can be used at the time of stent deployment enables the assessment of multiple factors regarding the vein and disease itself.

Regardless, Abramowitz noted that the IVUSbased scoring system needs further validation, either in the form of retrospective or prospective examination, potentially by expanding into other institutions. During the audience discussion, further remarks for future improvements involved controlling for the type of anticoagulation in patients—which was not controlled for in this study. Nonetheless, comments were suggestive of how IVUS may help decrease the variability that iliac lesions are being treated with across different specialties, in turn optimising treatment strategies for the future.

Early ultrasound surveillance key to predicting risk of re-intervention in deep stenting patients An analysis of post-thrombotic disease patients who received a nitinol stent has found that ultrasound surveillance should occur at frequent intervals up to two weeks post-procedure to predict risk of re-intervention.

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he results of the study were presented at the Royal Society of Medicine (RSM) Venous Forum annual meeting (25–27 June, London, UK) by Adam Gwozdz, clinical research fellow at St Thomas’ Hospital, King’s College London, London, UK. Gwozdz pointed out that endovenous nitinol stents for the treatment of postthrombotic syndrome is associated with symptomatic improvement, but that around “40% require re-intervention to maintain stent patency, and maybe duplex ultrasound surveillance is necessary to maintain stent patency.

Successful recanlisation depends on early intervention, and we know from experience that we are unable to recanalise blocked stents that are more than six weeks old, and therefore early intervention is key”.

The aim of this study, therefore,

was to examine whether ultrasound surveillance was sensitive for reintervention, and whether it was possible to predict which patients had the greatest risk of re-intervention.

To conduct the study, Gwozdz and colleagues at St Thomas’ Hospital included consecutive patients with post-thrombotic disease treated with a nitinol stent between 2012 and 2017.

Stent patency was assessed during duplex ultrasonography at 24 hours, two weeks, six weeks, three months, six months, one year and then annually after the procedure. Re-interventions were performed when there was a stent diameter reduction of >50% or occlusion.

Of the 194 patients treated, cumulative patency was 86% (median follow-up 2.4 years; range 34–295 weeks). However, Gwozdz et al found

that 79 patients required re-intervention to maintain patency, of which 51% (40/79) occurred within three weeks of their procedure. Further, they observed that stenting across the inguinal ligament was associated with a higher risk of early re-intervention.

Highlighting the importance of timely ultrasound surveillance, Gwozdz reported that re-interventions immediately followed ultrasound surveillance in 87% (70/79) of cases, and this was driven by scan results rather than symptom change. At six weeks post-procedure, in-stent stenosis of <30% was a strong predictor of being low risk for re-intervention at six months. Conversely, patients with in-stent stenosis between 30–50% at six weeks were at high risk of requiring reintervention at six months.

“Taking these results together, our recommendations are that having an ultrasound surveillance programme is an important component of deep venous stenting and that all patients should have surveillance up to two weeks post-

Adam Gwozdz

procedure. Patients with 0–30% in-stent stenosis at six weeks are at low risk of requiring re-intervention and do not need further surveillance until six months, and patients with 30–50% instent stenosis at six weeks are at high risk of requiring re-intervention and they should have further surveillance at three months,” Gwozdz concluded.

6

Sept

18

Venous leg ulcers

Issue

7

Cambridge study calls for improvement to care pathways for leg ulcer patients A Cambridge study has found that most inpatients with leg ulcers at one hospital were not referred to a vascular surgery team, indicating a need to improve pathways of care for inpatients with leg ulcerations.

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he results of the study conducted at Addenbrooke’s hospital, Cambridge, UK, were presented at the Royal Society of Medicine’s Venous Forum annual meeting (RSMVF; 25–26 June, London, UK) by Edward Lewis, fifth year medical student, University of Cambridge, UK. According to Lewis, leg ulcers are an increasing problem in the Westernised world. The associated health costs are significant and treatment is suboptimal, often resulting in limb amputations. The management of leg ulcers involves medical optimisation and urgent vascular surgical input. However, he noted, patients are often not identified early, so this study was conducted to discover the prevalence of leg ulcers in Addenbrooke’s hospital.

“We wondered whether there was a hidden burden of leg ulcer disease in the hospital which should be picked up by inpatient services. So we wanted to ascertain the burden of this disease in the inpatient population of a

large teaching hospital,” Lewis explained.

On a single day (4 January 2018), the entire inpatient population of Addenbrooke’s hospital was analysed.

Using the hospital’s computer system (EPIC), every patient had their record searched using the terms “ulcer”, “leg ulcer” and “foot ulcer”. Any patient who was younger than 55-years-old was excluded.

Each patient’s notes were reviewed to confirm an active leg ulcer and any medical comorbidities. The data collected included the ward, age and diabetes diagnosis.

Lewis reported that of the 979 patients in Addenbrooke’s hospital, 733 (74.9%) were eligible for inclusion. Of these, 75 (10.2%) had a current leg ulcer. Thirty nine of these patients had a diagnosis of diabetes, equalling 52%.

“Only 16 of these 75 patients were on a vascular surgery or diabetic foot ward, indicating that there was a large portion of this population who were not

under direct care and may not have been referred appropriately,” Lewis maintained.

Unhealing leg ulcers cost the UK National Health Service £3.2 billion/year (Guest et al 2015). This study showed that diabetes contributes in up to half of patients’ ulcers.

“In conclusion, we have discovered a very high burden of lower extremity ulcers in an inpatient population. A lot of these patients were not under a vascular surgery or tissue viability team. We therefore show that there is a definite need to improve patient pathways for referral in order that these inpatients can access vascular surgery services easily,” Lewis reported.

He added that what the research team is working on now is an algorithm for a referral pathway that can be used by healthcare professionals to expediate referrals.

“We realise that if all of these patients identified with an ulcer were referred, this would overwhelm the vascular surgery services. This algorithm provides a useful tool so that we can stratify the patients who need urgent referral and those who can be delayed.

Ultimately, we want to make sure that those patients have the right referral at the right time,” Lewis said.

Radiofrequency ablation plus compression outperforms the gold standard treatment for venous ulceration Although the multicomponent compression bandage is still regarded as the gold standard for the treatment of venous ulceration, the VUERT trial (Effects of saphenous and perforating veins radiofrequency ablation in ulcer healing) takes this into question, with mid-term data indicating that patients treated with combination therapy had better outcomes. The findings of this randomised controlled trial were presented at the Society for Vascular Surgery Vascular Annual Meeting (VAM; 20–23 June, Boston, USA) by Igor Sincos from the University of São Paulo Medical School, São Paulo, Brazil.

V

enous leg ulcers can take several weeks to heal, typically resulting in repeated cycles of ulceration, healing and recurrence, leading to high treatment costs and a negative impact on patients’ quality of life. Sincos et al’s study aimed to increase these healing rates, by pairing surgical radiofrequency ablation with a compression bandage system.

The study was a prospective randomised control trial of 56 patients with venous leg ulcers treated between January 2015 and August 2017 at the University of São Paulo Medical School. The inclusion criteria meant that the patients had to have one or more unhealed venous leg ulcer present for at least four weeks, as well as having great saphenous vein and/or small saphenous vein insufficiency plus perforating vein insufficiency.

Twenty-nine patients were allocated to the multicomponent compression bandage alone treatment group, and 27 were allocated to the combined surgical (radiofrequency ablation) and compressive treatment. All patients were stratified by ulcer duration (greater

or less than six months) and ulcer area (greater or less than 5cm). Whilst the primary endpoints included ulcer healing after six, 12 and 24 weeks, as well as ulcer recurrence after 12 months, secondary endpoints included ulcer healing velocity, VCSS (venous clinical severity score) improvement, quality of life (QoL) evaluation and economic evaluation.

Regarding the VCSS, both groups had a significant improvement in scores following the treatment. However, when analysing the recurrence rates of the patients in each treatment—the data showed a statistically significant difference in recurrence rates between the two conditions, with only one patient having a recurrence in the radiofrequency and compression group, compared with 12 patients in the isolated compression treatment group.

Although there were no statistically significant differences between groups in ulcer healing rates after six weeks, the 12 and 24-week venous ulcer healing rates were significantly greater in patients treated by endovenous radiofrequency ablation of saphenous and perforating

Igor Sincos

veins plus two-layer compressive bandages, compared with patients who were treated with compression alone.

For example, after 12 weeks, 73% of surgically treated patients had their ulcers healed versus 65% of compression alone treated patients, whilst after 24 weeks, the difference in healing rates became even more evident (100% vs. 76% for compression alone).

Despite the fact that these are mid-term results, Sincos said that the difference in these healing rates is expected to be

maintained until the end of the study.

He maintained that radiofrequency ablation can be a safe and effective way to treat saphenous and perforating insufficient veins in CEAP 6. Not only can the method be performed in damaged skin, findings suggest it avoids ulcer recurrence and could additionally help ulcer healing.

The findings of this trial were also presented by Juliana Puiginna at the American Venous Forum (AVF; 20–23 February, Tucson, USA).

Sept

18

Issue

7

Varicose veins

7

Combining VVSymQ and VCSS scores: A valid method to predict disease severity in varicose vein patients?

The utility of combining patient- and physician-reported scores to stratify disease severity and treatment rationale in patients with varicose veins has been highlighted in a recent study by Lowell Kabnick, Thomas Wakefield, Mikel Sadek, Jose Almeida and Glenn Jacobowitz, which sought to develop a tool for differentiating between patients with mild varices, and those with moderate to severe disease in need of intervention. Sadek (NYU Langone Health, New York, USA) presented the findings at the European Venous Forum annual meeting (EVF; 28–30 June, Athens, Greece). In discussion with the audience, concerns emerged regarding combining the two scores, as well as factors affecting insurance-covered and reimbursable treatment options for varicose veins, as Sadek argued “it is difficult to distinguish a truly symptomatic patient from one who wants treatment for cosmetic reasons”.

A

ccording to Sadek, there is a significant variation in the literature regarding management strategies and the threshold for intervention in patients with varicose veins: world-wide surveys show dramatic differences in how disease is treated in various countries. A paper from China illustrated this, showing that varicose veins—or CEAP clinical class 2 (C2) venous disease—is more aggressively treated in coastal China, with minimally invasive techniques used for less severe presentations, whereas open-surgical techniques for more severe presentations are used in Central and Western China.

This issue also extends to Europe, where the number of C2 patient treatment increases with a four-fold difference in the UK, Sweden and Finland as compared to the other European countries. Commercial and financial implications that dictate the management of varicose veins, Sadek noted, only heightens the discrepancy in treatment strategies.

“No single assessment tool provides accurate scoring for disease severity; most clearly exemplified by the variability seen in C2 patient clinical presentations,” Sadek added, which he argued has resulted in inconsistent treatment algorithms, patient care and payer reimbursement in the USA. The purpose of Sadek and colleagues’ study was therefore to generate an algorithm that incorporates patient-reported scores using the Varicose Vein Symptom Questionnaire (VVSymQ) and physician-reported scores, using the Venous Clinical Severity Scores (VCSS), in order to improve stratification for disease severity in C2 patients.

The VVSymQ, which relies on the HASTI symptoms—heaviness, achiness, swelling, throbbing and itching—from a validated questionnaire set (developed by BTG) that came from patients directly, was initially devised from the VANISH 1 and VANISH 2 trials. Alongside this measurement, both the VCSS and the CEAP tools were used for assessment.

Consecutive patients with symptomatic varicose veins were included in this multicentre study pooled from the VANISH 1 and 2 cohorts. Patients

Mikel Sadek

completed a seven-day electronic daily diary (the VVSymQ) to capture the type and severity of symptoms, including reporting on the HASTI symptoms.

The relationships between the VCSS and the VVSymQ were evaluated using Pearson’s correlation. The authors also performed a frequency distribution analysis used to classify patients according to VCSS and VVSymQ. Of the patients pooled from the VANISH 1 and 2 cohorts, 210 patients were identified with C2 disease; 73% female, with a mean age of 50 years.

The scoring systems revealed the mean score for VCSS was 6.32 (range: 3–16) and 8.72 for VVSymQ (range: 1.29–22.86). This indicated a weak correlation between VCSS and VVSymQ scores (r=0.22, p=0.05), which led the authors to suggest that taking the scores independently would be an invalid assessment of disease severity.

The frequency distribution analysis indicated that 61.4% of patients had a low VVSymQ and VCSS score, indicative of mild symptomatology.

Additionally, 31.3% of patients had increased VCSS (range 7–9) and VVSymQ scores (mean score 10.7), demonstrating daily symptoms of moderate severity. Furthermore, 7.3% of patients had VVSymQ and VCSS scores that were inconsistent for patients with C2 disease.

Based on these results, the authors reported that only a minority of patients fell into this category of VCSS greater than 10, meaning that these patients need to be

reassessed and in fact, Sadek explained, “most of these patients did not have C2 disease on review of the source data”.

In relation to mild symptoms (VCSS scores of 6 or less), there was a good correlation with low VVSymQ scores, as most of the averages fell below 7 or less. The patients with clinically significant disease from a physician’s perspective with VCSS scores of 7–9 similarly correlated with the average VVSymQ score of 7 or greater. The cumulative average of the three was 10.7; suggesting the scoring systems correlate well together.

The authors conclude that these data highlight the utility in combining patient reported scores and physician reported scores in order to stratify for disease severity and treatment rationale in patients with varicose veins. Specifically, for patients with combined elevated VCSS and VVSymQ scores, moderate to severe disease severity is corroborated, and interventional treatment may be warranted. For patients who do not meet the combined score criterion, the disease severity is likely mild and conservative therapy such as lifestyle modification and compression treatment may be the more appropriate treatment, yet this remains a topic of debate, as highlighted in the audience discussion outlined below.

Moving forward with this algorithm and combined approach, Sadek noted that additional prospective and populationbased studies are required to validate the efficacy of this approach.

During the discussion, members of the

audience raised some important issues regarding the criteria for patients to be considered for treatment. Although patients enrolled in this study needed a VCSS score of 7–9 for treatment to be considered, one audience member reitrated that “in the majority of studies including patients with C2 disease, the VCSS needed for treatment is lower.” However, Sadek maintained that the higher threshold for treatment is more in line with current debate in the USA, which he says is about whether to include any C2 patients at all in reimbursement and insurance coverage. In order to be able to “lead this discussion rather than to have it lead for us and completely eliminate the treatment of C2 disease all together”, the authors opted for a more conservative higher threshold. As a result, Sadek noted only approximately one third of patients evaluated in the study were treated with interventions, and added “whether it is appropriate or not, I think that is what need ongoing validation… perhaps the threshold is too high, but it is tough to tell without more data.” On further questioning, Sadek suggested that maybe the criteria should be modified so the number of patients considered appropriate for treatment is adjusted to 50–70% of patients with varicose veins.

“It is hard to distinguish a truly symptomatic patient to one who wants treatment for cosmetic reasons”, Sadek explained, and added that “physicians must be selective” due to financial, political and “all sorts of pressures” currently pushing in the direction of no treatment. Additionally, he noted that although the authors know a certain percentage of patients will deteriorate to C3 and C4 over time, they are unsure as to whether an interventional treatment strategy will decrease this risk overall.

Audience discussion further highlighted the difficulties of correlating symptoms and signs, and whether these should remain separate in assessments.

Sadek acknowledged that they in fact do not correlate, yet suggested that this was almost a justification in combining them, as it resulted in a clinically significant cohort. He recognised that this is a challenging topic—whether it is valid to combine them to begin with.

He reiterated, however, that “this just happened to be one method that seemed to find a clinically significant cohort of patients, from both the patients’ and physicians’ perspective.”

Sadek concluded that the data presented are indicative of one hypothesis-generating idea, meaning additional prospective studies are undeniably needed to validate the efficacy of this approach.

8

Sept

18

Venous stenting

Issue

7

ADVERTORIAL

Four-month follow-up for first procedures using blueflow Venous Stent The blueflow Venous Stent developed by plus medica GmbH & Co. KG received CE mark in early 2018, and has now been used in 60 patients at two centres in Europe. The stent utilises a woven nitinol design, which comes in different diameters and lengths to treat chronic venous outflow obstructions. The dedicated venous indication works as an extension stent, suitable for treatment below the inguinal ligament.

Case report 1 Dr Michael Lichtenberg

Figure 1

Nils Kucher

Michael Lichtenberg

Woven nitinol design combines flexibility with radial force

Dr Michael Lichtenberg, head of the Interventional Angiology and German Venous Center at Klinikum Arnsberg in Arnsberg, Germany, performed the first procedure with blueflow earlier this year.

Lichtenberg tells Venous News that one of the main advantages with the blueflow Venous Stent is its design: “A special characteristic of the nitinol woven design is that it is flexible, but with a strong radial force. We do not expect to see any stent fractures with blueflow.” He adds, “The woven design means we can place the stent exactly where it is needed, even in areas with high compression. It is particularly good for treatment below the inguinal ligament, as the stent gives high resistance to external force.”

Dr Nils Kucher (Clinic of Angiology, University Hospital Zurich, Zurich, Switzerland) agrees, saying “the blueflow stent is the only venous stent with a woven nitinol design, rather than steel alloy which compromises flexibility.

A benefit of this design is therefore that it has the great combination of flexibility and a strong radial force. For many indications in the venous system we do need both. We need to have flexibility, especially in the groin area, but you also have the inguinal ligament there which means that sometimes with conventional laser cut stents, we have observed stent fractures. We believe that with the blueflow Venous Stent we can avoid stent fractures, because woven nitinol can handle the force of external pressure which a laser cut stent cannot. This is one of the big advantages, and why we believe that this stent is the best stent available for the external iliac vein and the common femoral vein.”

A 44-year-old male patient with previous iliofemoral deep venous thrombosis of the right extremity, with persistent occlusion of the common femoral vein, external iliac vein and distal common iliac vein (Figures 1 and 2). Clinical symptoms included persistent swelling, lipodermatosclerosis and venous claudication (rVCSS 8, CEAP 4).

After recanalisation with a 14mm balloon, two overlapping blueflow Venous Stents (14x150mm and 14x60mm) were implanted, demonstrating good inflow and outflow (Figures 3 and 4).

Follow-up data show good patency at four months

“We now have some follow-up data for the patients treated in Arnsberg,” Lichtenberg says, “and all stents that we implanted are still patent, with no reocclusion. We did not have any feedback from patients about problems with the stent; no discomfort or pressure. Our latest follow-up was at four months.”

Kucher, who has now treated 12 patients with the blueflow Venous Stent, says he has used the device in several different scenarios, some more complicated than others, but even with difficult cases of severe obstruction he has managed to achieve “beautiful results” with this stent. “This is still early stages, but both Lichtenberg and I believe the device is an enriching addition to venous stents.”

Figure 2

Figure 3

“The benefit for us”, Kucher expands, “is that we now have an option with great flexibility for certain areas like with an occluded common femoral vein, but it can also be used for compressed veins, e.g. due to cancer.” Lichtenberg and Kucher both mentioned the stent is not indicated for May-Thurner and further investigations are needed, however, Kucher notes that “for all other indications I think the blueflow is a

Figure 4

great addition. In my opinion, there is not one stent that fits all venous disease. We have so many different indications, and of course this requires different stents, but I think in the future, this woven design will clearly have a place in the venous system.”

blueflow Venous Stent

Case report 2 Dr Nils Kucher A 62-year-old male patient with leg swelling and venous claudication.

He had a history of prostate cancer, tumour surgery and radiation therapy.

A CT scan and venography confirmed compression of the external iliac and common femoral vein.

After predilation with a 12mm balloon, a blueflow 14x100mm stent was implanted and then postdilated.

Final venogram confirmed good stent apposition.

The patients’ signs and symptoms of venous hypertension disappeared after the procedure.

Figure 1: Baseline venogram showing external iliac vein stenosis

Figure 2: Final venogram of the implanted blueflow stent in the external iliac vein

Figure 3: Fluoroscopic image of the implanted blueflow stent

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Issue

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Varicose veins

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Surgery better than foam sclerotherapy in patients with isolated AASV varicosis at one year One of the first randomised control trials comparing two therapeutic regimes—surgery and foam sclerotherapy—in patients with anterior accessory saphenous vein (AASV) varicosis, has found that surgery can outperform foam sclerotherapy in terms of duplexsonographic recurrence after one year. However, according to Stanislava Tzaneva (Medical University of Vienna, Vienna, Austria) who presented the study at the European Venous Forum Annual Meeting (EVF; 28–30 June, Athens, Greece) these findings do not extend beyond this time period; as surgery was considered comparable to sclerotherapy after three years.

T

he isolated anterior accessory great saphenous vein (AAGSV) varicose is characterised by reflux in the AAGSV, but sufficient great saphenous vein (GSV); a common pathway for both primary and recurrent varicose veins. The AASV reflux impairs a patients’ quality of life in the same way, however, the literature concerning patients with this condition is lacking, especially in relation to the optimal treatment.

A study carried out by Tzaneva et al aims to address this gap in the literature and provide answers regarding treatment for the condition by comparing two methods: crossectomy and avulsion of the varicose AASV under local anaesthesia, versus foam sclerotherapy of the AASV. The study was a prospective randomised controlled trial of 40 outpatients from the Medical University of Vienna, allocated either to the surgery group or the sclerotherapy group. The analysis found no significant difference between the median age, sex or body mass index, as well as diameter of the AASV, on the outcome measures. Follow-up was performed one and three years after intervention, with retreatment using foam sclerotherapy permitted at the first follow-up after one year.

The primary outcome measure was

duplexsonographic recurrence after three years— defined as reverse blood flow of >0.5 seconds along the AASV in the sclerotherapy group, or in new anterior thigh varicosities (NATV) connected to the previous saphenofemoral junction in the surgical group. Secondary outcomes included: duplexsonographic recurrence in the AASV or NATV after one year, clinical recurrence, as well as neovascularisation in the saphenofemoral junction after one and three years.

Of the 40 patients initially recruited, 38 patients (five males and 33 females) completed the study, with 20 in the sclerotherapy group and 18 in the surgery group. Results showed that after one year, significantly more patients in the sclerotherapy group revealed duplexsonographic recurrence compared to the surgery group (50% vs. 16% for surgery, p=0.029).

However, Tzaneva noted that if only clinical recurrence was considered, this difference was less (35% vs. 16% for surgery, p=0.021).

Additionally, after three years, duplexsonographic recurrence occurred in 52% of patients treated with sclerotherapy versus 22% of patients treated with surgery. Yet, this difference did not reach statistical significance (p=0.165). Regarding clinical

Stanislava Tzaneva

recurrences after three years, the presentation was equally distributed among both therapeutic groups: 35% in the scleotherapy vs. 22% in patients that underwent surgery (p=0.73). Lastly, neovascularisation at the groin occurred only after surgery: in 26% of patients after one year (p=0.018) and in 33% after three years (p=0.014).

Concluding her presentation on the outcomes, Tzaneva said that surgery was better than sclerotherapy in elimination of reflux in patients with isolated AASV varicosis after one and three years. However, she reiterated that this difference was only statistically significant after the one year follow-up. Additionally, if retreatment with sclerotherapy was performed or clinical recurrence was considered, the effectiveness of sclerotherapy was comparable to surgery after three years.

Study reports two- to three-fold reduction of varicose veins in pregnant women with compression therapy A new randomised controlled trial evaluated the preventative effect of compression stockings during pregnancy on the incidence of varicose veins as well as venous thromboembolism, with results suggesting that women with no venous disease using compression stockings during pregnancy were up to three times less likely to develop varicose veins. The results were presented by Dragan Milic (Medical Centre of Nis, Nis, Serbia) at the European Venous Forum annual meeting (EVF; 28–30 June, Athens, Greece).

“V

aricose veins develop in 8–20% of pregnant women,” Milic stated at the EVF meeting, noting that pregnancy increases the risk of venous thromboembolism (VTE) four- to five-fold as compared to the nonpregnant state. For varicose veins, risks increase with each pregnancy, developing in 13% of primiparous women, 30% of secundiparous women, and reaching up to 57% in multiparous women. Milic explained that varicose vein risk factors related to pregnancy include increased blood volume, high progesterone levels “allowing veins to stretch more than the normal state,” and “pressure exerted on the pelvic veins by the enlarging uterus, which causes obstruction of the flow of venous blood out of the legs.” The effects of pregnancy can result in sustained high pressure in the veins, causing them to stretch.

The study by Milic et al randomised 146 participants into three arms: group A (n=46), which prescribed Class 1 thighhigh elastic stockings with a compression of 17–20mmHg; group B (n=49) which prescribed Class 2 thigh-high elastic

stockings with a compression of 20–25mmHg; and group C (n=51), a control group which received no compression therapy. Participants were a mean age of 25 years, in fetal gestation between 6–10 weeks at enrolment, with healthy veins. This was defined as “no visible or palpable signs of venous disease, no previous history of venous disorders and normal duplex scan vein examination.”

Participants receiving compression therapy were instructed to wear compression stockings during the day, worn daily until time of delivery. One pair of stockings were provided per participant, and changed after four months.

Main outcomes were incidence of varicose veins, superficial thrombophlebitis and deep venous thrombosis.

Only one patient, enrolled in the control group, presented with thrombophlebitis. The study was therefore unable to observe any statistically significant differences or make any powered comparison for this outcome. Varicose veins, meanwhile, were developed in 14 patients of the control group (27.46%) versus five in group A (14.28%) and three

in group B (8.82%). This statistically significant difference between the arms led Milic to conclude that “the results obtained in this study suggest that compressions hosiery may reduce by two- to three-fold the incidence of varicose veins in pregnant women.”

However, of the initial 146 enrolled participants, only 121 completed the trial. “Drop-out rate was really high due to non-compliance,” Milic explained, with 11 participants in group A (23.91%) and 15 in group B (30.61%) unable or unwilling to wear the compression stockings for more than 50% of the time throughout the study period, or were without compression for more than seven consecutive days.

“I think the biggest problem in compression therapy is non-compliance”, Milic noted, pointing to the prevalence of the problem in other compression therapy trials as well as in real-world data.

In the discussion following Milic’s presentation, Marianne De Maeseneer (Erasmus MC, Rotterdam, the Netherlands) questioned the choice of using thigh-high compression stockings in the study, as “several studies have shown there is no difference in prophylactic effect between below-the-knee and thigh-high compression stockings,” but importantly, below-the-knee length stockings are often considerably more bearable for daily use. For compression therapy patients and pregnant women in particular, De Maeseneer said, below-the-knee stockings are likely to be more bearable in terms of comfort and ease of use.

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Interview

Profile

Kathleen Gibson

An accomplished vascular surgeon and prominent clinical researcher in the venous field, Kathleen Gibson (Lake Washington Vascular Surgeons, Bellevue, USA) plays an active role in a range of venous and vascular societies, and is currently involved in developing standardisation of definitions and tools for treating pelvic venous disease. In this interview, Gibson speaks to Venous News about her mentors, research interests, and the International Pelvic Vein Work Group.

What led you to become a doctor, and why did you choose to specialise in vascular surgery and the venous field?

My first interests were maths and science, and I first obtained a degree in Chemical Engineering. I enjoyed the challenges of engineering, but also had an interest in medicine, as I enjoy more direct personal interactions, so I decided to apply to medical school. I became interested in vascular surgery because of several factors: strong mentorship from Dr Eugene Strandness (a pioneer in our field), the attraction of the long-term relationships vascular surgeons have with their patients, and the intricate and complex nature of vascular procedures.

I still practice both arterial and venous surgery, but most of my clinical research interests have skewed towards the venous side of the field. I enjoy treating venous patients, as it allows me to have a significant impact on the quality of life of patients across nearly all age ranges, both healthy and ill.

What mentors have influenced you in your career and what did you learn from them?

My two most important mentors were Dr Eugene Strandness and Dr Mark Meissner. I was the first female Vascular Surgery Fellow at the University of Washington, much because of Dr Strandness’s encouragement. He taught me how to be a critical thinker, but an even more important lesson I learned from him was how to be kind and supportive of those around you. Dr Strandness was extremely supportive of the residents, fellows and vascular technologists working for him. A lot of his colleagues remember him as a great thinker and a hard-nosed interrogator at meetings, but he had a softer side. He knew the names of the housekeeping staff at the hospital and held a baby shower for me when I was in his lab.

Dr Meissner is both a mentor and a good friend. He trained under Dr Strandness as well, but was several years ahead of me. When he was a junior faculty member, I operated with him frequently and learned from his technical expertise—but I actually have learned more from him since I have been out in practice. He has been nothing but supportive of me and my career, and he is one of the smartest people I know. He has led me by his example to continue to be intellectually curious, and to always place my patients first.

What are your current areas of research?

On the arterial side, I am the principal investigator for the CREST II trial (carotid endarterectomy vs. stenting vs. medical management) for asymptomatic carotid disease and the COMPASS trial investigating the use of aspirin and Factor Xa inhibitors for the prevention of cardiovascular events.

In the venous space, I am currently involved in the venous stenting trials, and treatment of superficial venous disease with both truncal ablation and perforator treatment.

Which area of venous research do you think currently shows the most exciting or important developments?

I think some of our most exciting developments

will be coming over the next decade. With the increased interest in venous disease in the pelvis and abdomen—both reflux and obstruction—it will be critically important to have quality research that shows us how best to treat these patients.

In the last year, which papers have you found the most important for the venous field?

Two papers that I think will have significant impact are the ATTRACT trial (published in the New England Journal of Medicine in December), and the EVRA trial (published in the same journal in May). Although there are arguments that the protocols used in the ATTRACT trial are no longer up-to-date with current techniques, I think it will influence which patient groups are offered thrombolysis for acute deep venous thrombosis.

The EVRA trial showed that early endovenous ablation resulted in faster wound healing in patients with venous ulceration compared to delayed ablation—findings which may change treatment strategies for patients with advanced venous disease.

You have recently started the International Pelvic Vein Work Group together with colleagues from several different institutions. What is the aim of this initiative?

The aims of the initiative at this time are: to establish evidence-based disease definitions for pelvic venous disorders; develop discriminative tools, e.g. to categorise the various forms of pelvic venous disorders, analogous to the CEAP model for lower extremity venous disease; and develop validated disease-specific health related quality of life outcome measures that can be used as a primary endpoint in clinical trials, including drug and device trials to support labelling indications.

One of the main problems in vein care today is that there is no standard of practice in this space. While pelvic venous disorders are increasingly recognised and studied, a lack of standard terminology has hampered our understanding of the best practices for treating these patients.

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Fact File

Why do you think it is important to ensure the Work Group is interdisciplinary, and are there any challenges in that aspect?

There are many specialty groups that have an interest in the treatment of patients with pelvic venous disease. Buy-in of all physicians who care for these patients is important, in order to understand how to best develop these tools and to lead to widespread adoption by clinicians and researchers.

Standardised and validated

tools will allow us to gather the high-quality evidence needed to create guidelines for the diagnosis and treatment of patients with pelvic venous disorders across specialty groups.

Currently, the groups we have approached include representatives from the American College of Phlebology (ACP), the Society of Interventional Radiology (SIR), the American Venous Forum (AVF), the International Union of Phlebology (UIP), the European Venous Forum (EVF), the American College of Obstetrics and Gynecology (ACOG), Cardiovascular and Interventional Radiology Society of Europe (CIRSE), the International Pelvic Pain Society (IPPS), Korean Society of Interventional Radiology (KSIR), and additional organisations from Latin America and Asia.

We had a recent international meeting in Chicago, and having a multidisciplinary group was of great value—all specialists fully participated and provided an incredible breadth of experience and perspective.

What is next for you in your research?

Currently, I am working on collecting five-year data for the VeClose Venaseal (Medtronic) versus radiofrequency ablation trial, finishing enrolment for the Abre (Medtronic) venous stent trial and potentially starting several new trials next year. I am also working on writing manuscripts for the recently completed SECURE trial on laser ablation for perforator veins, and the one-year results of the WAVES Venaseal trial.

What advice would you give to someone interested in specialising in venous disorders?

Always listen to your patients: treat what is bothering them, not just what is abnormal on imaging. Make sure your treatment is always patient-centred and you are performing it for the right reasons. Be knowledgeable about the whole spectrum of venous disorders: if you do not have the expertise to manage a particular disease state, be sure to know where to send your patient.

What was the most memorable case of your career, and why?

Usually the cases that go wrong are the ones that stay with you, but one of my most memorable cases that had a happy ending was a successful deep venous stenting case for a young man who had significant venous claudication several years following a postsurgical iliofemoral deep venous thrombosis. He was on active duty with a marine search and rescue team and could no longer meet the physical training requirements, and therefore was in danger of having to end a career that he loved. Six months after his stenting (because he could not go to work on full anticoagulation), he was able to pass his personal training requirements and go back to work.

How do you prefer to spend your time outside of work?

An answer commonly given in interviews but absolutely true—I most enjoy spending time with my family: my husband, two children and three dogs. We all enjoy travelling (usually without the dogs) and have been on many adventures around the world. One of my favourite quotes is, “travelling is one of the few ways you can spend money yet grow richer.”

Current appointments (selected) 2014-

2014-

2013-

American College of Phlebology: Scientific Committee American College of Phlebology: Guidelines Committee American Venous Forum: Membership Committee, 2018 Chair

Education

2011 Endovascular Fellowship: Kaiser

Permanente Hospital, Honolulu, USA 2001 Vascular Surgery Fellowship: University

of Washington School of Medicine,

Seattle, USA 1994-99 General Surgery Residency: University

of Washington School of Medicine,

Seattle, USA 1990-94 MD: University of Washington School

of Medicine, Seattle, USA 1989 BS Chemical Engineering: University of

Washington, Seattle, USA

Board positions

2015- Board of Directors: American Board of

Venous and Lymphtatic Medicine 2014- Board of Directors: American College of

Phlebology 2010-13 Board Member: Overlake Hospital

Medical Center

Committees and editorial boards (selected)

2018- International Pelvic Vein Work Group

(co-sponsored by ACP and SIR) 2018 Program committee and registry

research co-chair: American College of Phlebology 2014- Vein Magazine: Medical Advisory Board 2013- European Journal of Vascular and

Endovascular Surgery: Selected Reviewer

Society affiliations

Society for Vascular Sugery American Venous Forum American College of Phlebology European Venous Forum Western Vascular Society Pacific Northwest Vascular Society Fellow, American College of Surgeons Alpha Omega Alpha Henry Harkins Society Washington State Medical Association

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Superficial vein thrombosis

Issue

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Current aspects in the management of superficial vein thrombosis ATHANASIOS GIANNOUKAS COMMENT & ANALYSIS Superficial vein thrombosis is not a rare disease, with an incidence of 0.64 in 1,000 annually.1 The POST, OPTIMEV and STEPH studies have shown that superficial vein thrombosis may be associated with a considerable risk of concomitant deep vein thrombosis (24.9–26.3%) or pulmonary embolism (3.9–6.8%).1-4 Additionally, even in the case of isolated superficial vein thrombosis, the risk of a subsequent symptomatic deep thrombosis or pulmonary embolism three to six months later is still high (0.6–3.1% and 0.3–0.9%, respectively).4 These observations underline the importance that superficial vein thrombosis should no longer be considered as a separate entity, but as part of venous thromboembolic disease such as deep vein thrombosis (DVT) and pulmonary embolism.

T

he most important consideration is whether superficial vein thrombosis develops in the presence of varicose veins or not. In the absence of varicose veins—which is less frequent, consistuting onle 5–10% of all superficial thromboses), the main saphenous trunk is very often involved and the possibility of the presence of malignancy, hypercoagulability and autoimmune disease should be investigated.5–7 In the presence of varicose veins, which is the most frequent scenario, superficial vein thrombosis is commonly confined to greater saphenous vein tributaries and in 5–10% may affect both limbs.2,8,9 In the course of diagnosis, colour flow duplex imaging is recommended for the confirmation of diagnosis and the extent of thrombosis, as well as for the exclusion of concomitant DVT and in follow-up.

In the management of superficial vein thrombosis there is no place for antibiotics unless there is history of placement of indwelling catheters in the affected veins.

The role of aspirin and non-steroid anti-

inflammatory drugs orally or locally and hirudoid locally is not well-defined and they are mostly used to alleviate pain and local inflammatory signs.

When superficial vein thrombosis coexists with DVT or when the extent of thrombus is close to saphenous junctions (<3cm), treatment with low molecular weight heparins (LMWHs) in therapeutic doses for three months is recommended.10 For superficial vein thrombosis away from the junction (>3cm) and with thrombus extent more than 5cm, 2.5mg of Fondaparinux for 45 days is recommended on the basis of the Calisto study.11 However, the results of this study attracted criticism, as such long-time treatment of all superifical thrombis cases in real-world practice may not be necessary, as well as issues with cost-effectiveness.12 As it has been demonstrated, treatment with intermediate doses of Tinzaparin for about two weeks was effective in about a third of superficial vein thrombosis patients, especially when the thrombosis was confined to below-the-knee veins and the patients were sufficiently mobilised.13

The use of intermediate doses of LMWHs for at least one month is recommended as compared to prophylactic doses for shorter periods.10,14 In a recent study, it was demonstrated that extended threemonth treatment with Tinzaparin in intermediate doses was more effective in terms of venous thromboembolism recurrence as compared to two-month treatment with variable Tinzaparin dose (0% vs. 15.3%, p=0.004).15 Interestingly, in the placebo group of the Calisto study,11 subgroup analysis showed an increased incidence of symptomatic venous thromboembolism complications at day 47 if one of the following characteristics was present at inclusion: age >75 years; BMI ≥30kg/ m2; CrCl <50mL/min; history of DVT or pulmonary embolism more than six months previously; history of superficial vein thrombosis more than three months previously; absence of varicose veins at inclusion; superficial vein thrombosis above the knee; superficial vein thrombosis involving the great saphenous vein; distance between the thrombus head and the saphenofemoral junction <10cm.

The Surprise study, a recent noninferiority study comparing 10mg oral administration of Rivaroxaban once daily versus subcutaneous administration of Fondararinux 2.5mg once daily for 45 days, showed that Rivaroxaban was not inferior in preventing venous thromboembolism complications in high-risk patients.

During treatment in both groups venous thromboembolism was very rare but DVT occured slightly more frequently in the Rivaroxaban group (3/211 vs.

1/224). No major bleeding occured and the incidence of minor bleeding until day 45 was the same in both groups (6%), but the clinically relevant nonmajor bleeding occured more often in the Rivaroxaban group (6/211 vs.

1/224). Additionally, during follow-up a rebound phenomenon was present in both groups resulting in primary efficacy

outcome after 90 days in 15 patients (7%) in both groups. Again, DVT was more frequent in the Rivaroxaban group (6/211 vs. 2/224).16 Finally, surgical treatment with elastic stockings was associated with lower venous thromboembolic rate and superficial vein thrombosis progression compared to elastic stockings alone,17 while a review of six studies comparing surgical therapy to anticoagulation showed that surgery was superior in rapid symptom relief, but was associated with higher incidence of venous thromboembolism and complications.18 In summary, venous thromboembolic complications of superficial vein thrombosis are not infrequent and highrisk patients, who may need a prolonged treatment, while in intermediate and low-risk patients a prophylactic dose (2.5mg) of fondaparinux for 45 days or intermediate doses of LMWHs for a month is enough. Based on the existing evidence, superficial vein thrombosis should be considered as part of venous thromboembolic disease, like DVT and pulmonary embolism.

Athanasios Giannoukas is professor and head of the Vascular Surgery Department at University Hospital of Larissa in Volos, Greece References 1. Frappé P. et al. J Thromb Haemost 2014; 12:831–838.

2. Decousus H. et al. Ann Intern Med 2010; 152:218–24.

3. Galanaud JP. et al. Thromb Hemost 2011; 105:31–39.

4. Decousus H. et al. J Thromb Haemost 2015; 13 Suppl 1:S230–237 5. Decousus H et al. Thrombosis Research 2011; 127 (3) 81-85 6. D ecousus H et al. Curr Opin Pulm Med 2003;9:393–39 7. B elcaro G, Nicolaides AN, et al. Angiology 1999;50:523–529 8. L eon L, Giannoukas A, et al. Eur J Vasc Endovasc Surg 2005;29:10–17 9. Lutter KS, et al. Surgery 1991;100:42–46 10. I nternational Consensus Statement : Prevention and Treatment on Venouς Thromboembolism. Int Angio 2013;32:237-43 11. D ecousus H, Prandoni P, Mismeti P, et al. N Engl J Med 2010;363:1222-32.

12. Goldman L, Ginsberg J. N Engl J Med 2010;363:1278-80.

13. G iannoukas A, Karathanos Ch, et al. Phlebology 2017 doi:10.1177/0268355517748540 Epub ahead of print.

14. C osmi B et al. J Thromb Haemost. 2012;10:1026-1035 15. N ikolakopoulos KM, Kakkos S, Papageorgopoulou CP, Tsolakis I. Vasc Specialist Int 2018;34:1-9.

16. B eyer-Westendorf J, Gerlach H, Rabe E, et al. Lancet Haematology 2017;4:e105-e113.

17. D iNisio M, Wichers IM, Middeldorp S. Cochrane Database Syst Rev 2008;3;00075320-100000000-0401 18. Sullivan V et al. J Am Coll Surg 2001;193:556-562

“Substantial” symptomatic resolution at two years with Vici venous stent A recent study carried out by Stephen A Black and colleagues at Guy’s and St Thomas’ NHS Trust, Kings College London (London, UK) assessed two-year outcomes in patients with chronic iliofemoral venous occlusions with placement of the of the Vici venous stent (Boston Scientific). The data indicate that the stent is associated with a good secondary patency rate, as well as substantial symptomatic resolution.

T

he paper, published in the European Journal of Vascular and Endovascular Surgery, evaluated 88 patients (101 limbs) that were treated with the stent placement between March 2014 and October 2016 for venographically verified iliofemoral venous occlusion and post-thrombotic syndrome, at least 12 months after acute deep vein thrombosis, with a Villalta score of ≥5 points. Venography and intravascular ultrasound were used peri-operatively, while duplex ultrasound was used to subsequently assess stent patency during follow-up. In relation to patency, primary, assisted primary and secondary patency rates at one year were 59%, 78%, and 87%, respectively, and fell slightly to 51%, 73% and 82% at two years. Forty-three limbs (43%) had required re-intervention (lysis, venoplasty and/or placement of stent) during the follow-up period, with the median time for re-intervention at 32 days (range: 0–520 days). Another key finding was that at 24 months, 37 of 53 limbs (70%) with available Villalta score assessment showed clinically

significant improvement (>30% reduction of baseline score, with a median pre-treatment Villalta score of 14). Additionally, Villalta scores at the six, 12 and 24-month clinical follow-up were significantly lower than before stenting (p<0.001, for all time points).

Stenting extended across the inguinal ligament in 63 limbs (62%) in order to land in a healthy venous segment. In a subset analyses of limbs with stenting terminating above and below the inguinal ligament, secondary cumulative patency rates at 24 months were 90% and 79%, respectively; clinical outcome showed 58% versus 73% of limbs with clinically significant improvement, respectively.

The latter finding led the authors to conclude that the Vici venous stent is associated with particularly good secondary patency rates, as well as durable and substantial symptomatic resolution in patients with chronic post-thrombotic occlusions, regardless of whether stents extended beneath the inguinal ligament.

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AngioJet thrombectomy can reduce dose and duration of lysis compared to thrombolysis alone

Anna Louise Pouncey revealed at the European Venous Forum annual meeting (EVF; 28–30 June, Athens, Greece) the findings of the GSTT venous team (Guy’s and St Thomas’ NHS Foundation Trust & Kings College London, London, UK) that early use of adjuvant AngioJet thrombectomy (Boston Scientific) resulted in reduction in post-thrombotic syndrome, equivalent vessel patency, and a reduction in the overall dose and duration of lysis.

D

eep vein thrombosis (DVT) causes over 24,000 deaths a year in the UK, costing around £1 billion.

For patients who have an iliofemoral DVT, the risk of developing post-thrombotic syndrome is 50%, and can result in severe consequences. In light of this, the American Venous Forum recommends that physicians should attempt early clot removal with lytic techniques. Percutaneous catheter-directed thrombolysis is often used to treat acute iliofemoral DVT, but the efficacy of this treatment and adjunctive pharmacomechanical modalities is not yet determined.

Whilst catheter-directed thrombolysis uses a multiple side-holed catheter to infuse lytic agents into the clot directly, working to soften and break it down, AngioJet rheolytic thrombectomy uses pressurised saline jets, to macerate the thrombus and aspirate material back into the catheter. The AngioJet has an additional mode—the “powerpulse” mode; involving active spraying of lytic agent into the clot, allowing time for it to soften, and, “leading to more success when using the rheolytic mode”, Pouncey noted.

Pouncey and the GSTT venous team aimed to retrospectively compare the outcome of patients who had been treated with catheter-directed thrombolysis alone, to those treated with the addition of AngioJet pharmacomechanical thrombectomy. They performed a singlecentre retrospective cohort study, selecting all patients with symptomatic acute iliofemoral DVT treated between 2011 and 2017. A total of 151 cases were identified, consisting of 81 patients treated with catheter-directed thrombolysis and 70 with adjuvant use of AngioJet thrombectomy.

Patient demographics, duration of symptoms, thrombosis risk factors and modality of treatment were collected.

Four outcome measures were chosen: the incidence of post-thrombotic syndrome (measured by Villalta scores), primary, primary-assisted and secondary patency, lytic time and dose and the incidence of complications.

Baseline demographic data and prevalence of risk factors were comparable between groups. Incidence of postthrombotic syndrome, measured by Villalta score at six months and one year, were equivalent (p=0.028). The analysis of cases treated with catheter-directed thrombolysis versus AngioJet showed no significant difference in primary, primaryassisted and secondary patency over two years. Addition of AngioJet thrombectomy resulted in a reduction in lysis duration of

40 hours (95%, CI:34–46) versus 53 hours (95%, CI:49–58, p=0.0001) and a reduction in lytic dose: 49mg (95%, CI:42–55) compared with 57mg (95%, CI:52–61) for catheter-directed thrombolysis. This reduction was accentuated in cases initially treated with “powerpulse” AngioJet thrombectomy: 27 hours (95%, CI:20–34) and 42mg (95%, CI:34–50).

Incidence of complications were found to be comparable between groups, with a major bleed rate of 0.66%—a rate in line with the current literature. The incidence of haemaglobinuria was increased following AngioJet thrombectomy (18.6% vs. 3.7%), but, no statistically significant difference in acute kidney injury was observed (4.3% vs. 1.2%, p=0.244). A slight increase in minor bleeding occurred in the catheterdirected thrombolysis group, which could be attributed to longer lytic times.

One fatality—due to a haemorrhagic stroke—occurred in the catheter-directed thrombolysis group. This occurred three hours into lysis, due to an undiagnosed arteriovenous fistula. Overall, the authors felt there was an adequate safety profile for both treatment modalities.

Results from both catheter-directed thrombolysis and AngioJet cohorts had excellent Villalta scores and a low level of post-thrombotic syndrome. Both treatment modalities resulted in equivalent vessel patency. Importantly, the study found that AngioJet reduces lysis dose and duration, which is potentially cost-effective and safer for the patient. This improvement was accentuated in patients commenced on “powerpulse” mode, which reduced lysis time to just under 27 hours.

In relation to future implications, the GSTT venous team are currently conducting a health economic analysis, with a view to optimising the acute DVT pathway. With increasing pressures on the current health system, reducing patient transit time would be of great economic advantage, all-the-while providing as many as possible with improved symptomatic relief. The GSTT venous team attribute their low rate of post-thrombotic syndrome to attention to detail at every step of the patient journey. This includes judicious patient selection, early treatment, attention to anticoagulation, stenting healthy-tohealthy, and rigorous post-operative surveillance. Pouncey stated: “This is a moving field that is improving… attention to detail and discussion about the topic is important in terms of making sure we can all provide a better service.”

Thrombectomy

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Deep venous disease

Money boost for novel venous technologies

The past few months has seen several companies invest in new and emerging venous technologies.

For example, at the beginning of July, BD announced that it had completed its acquisition of TVA Medical—a company that develops, according to a press release, minimally invasive vascular access solutions for patients requiring haemodialysis. One such solution is the endovascular everlinQ system that been designed to create arteriovenous fistulas. Data presented at ISPOR 2018 (19–23 May, Baltimore, USA) indicate that the system provides quality-of-life benefits and cost savings compared to the traditional surgical approach in end-stage renal disease patients. Furthermore, in June of this year, the US Food and Drug Administration (FDA) gave de novo marketing approval for the system. Adam L Berman, co-founder of TVA Medical, comments: “The FDA authorisation and joining BD are the culmination of many years of hard work by a dedicated team of innovators at TVA Medical.”

Another company seeing years of hard work payoff is Veniti, who Boston Scientific recently agreed to acquire—although, of note, they have been an investor in Veniti since 2016 and currently own 25% of it.

Veniti developed and marketed the Vici venous stent, which received the CE mark in 2013, and submitted a pre-market approval application for the stent to the US FDA in June. “This stent system was designed with the distinctive demands of the venous system in mind, and built to provide physicians with a highquality lumen across a variety of venous anatomies and disease states. We are excited to see this stent technology become even more accessible to physicians and the patients they treat under the leadership of Boston Scientific,” says Veniti’s president and CEO Jeff Elkins.

Although it has not [yet] been bought out by a big-

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ger company, Venclose has also had something to celebrate. It announced in July that it had completed Series B financing from new and existing investors.

The company is in the process of commercialising the Venclose radiofrequency ablation system—designed to close damaged veins and restore healthy blood flow in patients with venous reflux disease.

As well as completing the series B financing, the company has made two new appointments: Jeffrey G Carr as chief medical officer and Gregory J Vislocky to the board of directors. In a press release, Vislocky states he is “honoured” to be on the board of directors and that “with its operational excellence and management team members’ proven track record, Venclose is well positioned to benefit a large patient population.”

Pipeline insights

For more details, see venousnews.com A new study, published in the New England Journal of Medicine and presented at the 2018 European Society of Cardiology (ESC) Congress (25–29 August, Munich, Germany), shows that a non-vitamin K antagonist oral anticoagulant (Xarelto, Bayer) reduces the risk of non-fatal blood clots and pulmonary embolism in medically-ill patients.

An IVUS-based scoring system could be used to predict venous stent failure in the treatment of MayThurner syndrome. Abramowitz S D. Presentation at Society for Vascular Surgery Vascular Annual Meeting (VAM; 20–23 June, Boston, USA).

A novel endovenous therapy technology (SnakeBack, LSO Medical)—a remote catheter removal system that is integrated with a laser ablation system and is designed to work automatically without the need for fibre tension or alignment—has the potential to reduce human error in the management of varicose veins.

Rochon P. Demonstration at the 2018 Charing Cross Symposium (24–27 April, London, UK).

BIBA Briefings

BIBA Briefings is a new platform that provides in-depth analysis of the latest market intelligence from BIBA MedTech, 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.

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

Early identification strategy of patients at high risk for iliofemoral DVT may need improvement According to Fedor Lurie (Jobst Vascular Institute, Toledo, USA), who presented at the European Venous Forum Annual Meeting (EVF; 28–30 June, Athens, Greece), patients with a high probability of iliofemoral deep vein thrombosis (DVT) are not diagnosed early enough in the USA, which can become problematic. The research presented by Lurie investigated a means of identifying the anatomical location of DVT using existing risk stratifications, with a view to expedite future diagnoses and treatment of iliofemoral DVT.

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n the USA, current guidelines recommend risk stratification of patients with suspected DVT, using a clinical decision rule (such as Well’s score) and D-dimer level. However, Lurie pointed out that this strategy results in early anticoagulation and a delay in imaging tests in high risk patients.

Additionally, specific management of patients with confirmed DVT depends on the anatomical location of the thrombus (iliofemoral, femoropopliteal, or calf), which, when known, can accelerate appropriate investigation and treatment.

Given that larger thrombus volume and acuteness of thrombosis in iliofemoral DVT should result in higher concentrations of circulating products of thrombus degradation, as well as how acute iliofemoral DVT is

usually more symptomatic compared to femoropopliteal or calf DVT—which should increase the value of the Well’s score—Lurie hypothesised that acute iliofemoral DVT is associated with higher levels of D-dimer and a higher Well’s score compared to femoropopliteal and calf DVT. A nested case–control study was performed, identifying a prospective cohort of 221 patients who had a positive duplex ultrasound performed within 48 hours from onset of symptoms, who were admitted to emergency departments of seven hospitals in Northwest Ohio and Southeast Michigan from 2014 to 2016.

Each patient was matched by age and gender with a control who presented negative for DVT in a 1:5 ratio, meaning the total number of controls was 1103.

The relationships between the anatomical location of DVT, D-dimer levels, and Well’s score were examined using parametric and non-parametric (for Well’s score) tests. Receiver operating characteristic (ROC) curves were analysed to identify the best cut-off values for both Well’s score and D-dimer.

Findings of the study show that among patients with positive DVT ultrasound scans, iliofemoral DVT was found in 75, femoropopliteal in 92, and calf DVT in 54 patients. Both D-dimer and Well’s score showed high diagnostic value for identification of iliofemoral DVT with areas under the ROC curves 0.9 and 0.8, respectively (p<0.0001).

Regarding the risk stratification instruments, only D-dimer was sufficiently sensitive to identify

femoropopliteal DVT (ROC area 0.8, p<0.0001), whilst neither D-dimer nor Well’s score had sufficient sensitivity to identify calf DVT (ROC area 0.6, p=0.1). Patients who had D-dimer of 700ng/ml or more were 22.5 times more likely to have iliofemoral DVT (OR=22.5, 95%, CI 11.2–45.1) and those who had D-dimer level between 500 and 700 were 9.5 times more likely to have femoropopliteal DVT (OR=9.5, 95%, CI 5.7–16.0).

Lurie concluded that the D-dimer is more sensitive to DVT level compared to Well’s score. Importantly, he reiterated that it is possible to identify patients at high risk for iliofemoral DVT based on D-dimer level, as the findings suggested that D-dimer levels of 700ng/ml or higher is more likely to be associated with iliofemoral DVT. Lurie pointed to the practical implications of these findings, in terms of the possibility of immediate intervention, given that the cut-off point for D-dimer can be used to identify high-risk patients for iliofemoral DVT.

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Clinical News Study proves need for anticoagulant strategy post discharge for hospitalised, atrisk patients

Alex C Spyropoulos, from Feinstein Institute for Medical Research (New York, USA), has uncovered an anticoagulant treatment strategy to reduce non-fatal blood clots and pulmonary embolism in acutely-ill hospitalised patients, according to clinical findings published in The New England Journal of Medicine. This treatment strategy is associated with almost no critical or fatal bleeding and with a very low incidence of major bleeding.

These results, which were simultaneously presented at the 2018 European Society of Cardiology Annual Congress in Munich, Germany, have the potential to reduce venous thrombosis and non-fatal pulmonary embolism in up to 30% of acutely-ill hospitalised patients. With eight million acutely-ill, hospitalised patients in the USA and another 12 million in the European Union, this novel treatment strategy could potentially prevent tens of thousands of symptomatic venous thrombosis events each year.

Venous thrombosis is a condition where a blood clot forms due to surgery, cancer, immobilisation and long-term hospitalisation. This clot can travel to the lungs and block blood flow, causing death from a condition called pulmonary embolism. Medically ill patients are at greater risk for developing blood clots while in the hospital and for up to three months afterward. Medications such as anticoagulants are often provided during hospitalisations, but some clinicians and researchers feel these medications could be beneficial for medically ill patients for up to six weeks after hospital discharge when they remain at greatest risk.

Spyropoulos examined whether administering the medication rivaroxaban would help prevent symptomatic venous thrombosis and death related to blood clots after patients are discharged from a hospital.

While the trial found the medication was unable to reduce death due to blood clots, the study did identify a potential treatment strategy for those with non-fatal blood clots.

“We were able to reduce instances of non-fatal blood clots and pulmonary embolism by more than half, which shows that the use of direct oral anticoagulants such as Xarelto after the hospitalisation of medically ill patients could help prevent clots from forming,” said Spyropoulos. “Our next course of research is to further identify and refine a post-discharge treatment programme which would maximise the net clinical benefit across a defined spectrum of medically ill patients.”

In this double-blind, randomised trial, 6,007 patients were given rivaroxaban and another 6,012 participants provided placebo while in the hospital and for 45 days after discharge. Of those patients only 0.18% in the rivaroxaban group suffered from non-fatal venous thromboembolism versus 0.42% of patients in the placebo

group, a statistically significant difference.

The incidence of major bleeding was very low and not significantly different between groups (0.28% in the rivaroxaban group vs.

0.15% in the placebo group).

“Dr Spyropoulos’ discovery of a new treatment avenue for blood clots has the potential to positively benefit patients across the globe,” said Kevin J Tracey, president and CEO of the Feinstein Institute. “He is a respected leader in this field.”

Direct anticoagulant for pulmonary embolism associated with reduced hospital time and costs

New data from the MERCURY PE study have shown that patients with low-risk pulmonary embolism who were treated with the direct oral anticoagulant rivaroxaban, trade name Xarelto (Janssen Pharmaceutical), and discharged from the emergency department had significantly reduced time in the hospital and a median savings of US$2,496 in per-patient costs, compared to standard of care in-patient treatment.

Results from MERCURY PE, which evaluated the benefits of treating patients with low-risk pulmonary embolism with Xarelto and discharging them early from the emergency department to complete treatment at home, were published in Academic Emergency Medicine.

“Every year, US healthcare systems spend more than two billion dollars to manage patients with pulmonary emboli,” said principal study investigator W Frank Peacock, associate chair and research director, Emergency Medicine, Baylor College of Medicine, Houston, USA. “By avoiding hospitalisations that are not clinically necessary and transitioning patients with low-risk pulmonary embolism to out-patient treatment with Xarelto, we have seen significant cost savings, which could help alleviate the burden on healthcare systems.”

Venous thromboembolism (VTE) includes deep vein thrombosis (DVT) and pulmonary embolism. Of the approximately 900,000 Americans who experience a VTE each year, more than 250,000 are diagnosed with pulmonary embolism in the emergency department. Hospitals across the USA have varying protocols for managing pulmonary embolism, but standard of care typically requires people to be admitted for treatment, which drives up costs and substantially increases hospital-acquired conditions and infections. While people with more severe pulmonary embolism have higher mortality rates, the 30-day mortality rate in low-risk patients is less than 1%.

MERCURY PE met its primary efficacy endpoint, with Xarelto leading to significantly reduced time in the hospital due to VTE or bleeding within 30 days after randomisation compared with the standard of care (mean duration of 4.8 vs.

33.6 hours, respectively; p<0.0001). The mean difference of length of stay between the two groups was 28.8 hours. Of note,

there was no recurrence of VTE or VTErelated death or any significant differences in the bleeding-related hospitalisations or physician visits within 90 days from randomisation in either group, though this outcome should be interpreted with caution, as the study was significantly underpowered to detect any such differences.

Patients with low-risk pulmonary embolism were randomly assigned in a 1:1 ratio to open label Xarelto or standard of care within 12 hours of diagnosis. Patients randomised to the direct oral anticoagulant were discharged from the emergency department within 24 hours and were instructed to take a 15mg dose, twice daily for 21 days, then 20mg once daily until the study was completed. Patients randomised to standard of care were treated per local hospital protocol, which could include hospitalisation and any US Food and Drug Administration-approved anticoagulant strategy, including Xarelto.

Researchers also made the following observations about the anticoagulant drug in this setting: The mean length of initial and subsequent hospitalisations for any reason was shorter for patients who were discharged early on Xarelto within 90 days from randomisation compared to those receiving standard of care (p=0.024; 19.2 hours vs. 43.2 hours, respectively).

There was no major bleeding in either group within 90 days from randomisation, although two patients reported clinically relevant non-major bleeding, one in each group. There were no deaths due to bleeding in the study.

Overall, early discharge on the direct oral anticoagulant was markedly less expensive than standard of care. The cost associated with the emergency room visit and any subsequent hospitalisation at the time of diagnosis and the total costs were US$2,638 (p<0.001) and US$2,496 (p<0.001) less compared to standard of care.

MERCURY PE builds on prior research, including a June 2015 study published in Academic Emergency Medicine showing that 106 patients with low-risk pulmonary embolism or DVT, when prescribed Xarelto and immediately discharged, had no recurrent events while on therapy.

Additionally, no major or clinically relevant bleeding events were observed. A companion study found patients with lowrisk pulmonary embolism or DVT who were prescribed Xarelto had significantly lower medical costs than those admitted and given standard treatment.

The clinical and economic benefits demonstrated in the MERCURY-PE trial have been confirmed in more than 3,100 US patients in a real-world study, showing that the anticoagulant resulted in a significant one-day reduction in hospital length of stay and significantly lower total healthcare costs (approximately US$2,000).

Edoxaban emerges as alternative to dalteparin for cancer-associated VTE

A new analysis has identified patient populations with cancer-associated venous

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thromboembolism (VTE) who could benefit from treatment with oral anticoagulant edoxaban, taken once daily.

Daiichi Sankyo has announced the publication of a new analysis, focusing on the clinical presentation, course and outcome of bleeding events, and the associated tumour types from the HokusaiVTE CANCER study. The data, published in the journal Thrombosis and Haemostasis, identified that edoxaban is an appropriate alternative to dalteparin and that further consideration is needed for the treatment of patients with gastrointestinal cancer.

The study found that the rate of recurrent VTE was 3.4% lower with edoxaban compared to dalteparin (hazard ratio [HR]:0.71; p=0.09), whilst the rate of major bleeding (as defined by the International Society on Thrombosis and Haemostasis [ISTH]), was 2.9% higher (HR:1.77; p=0.04). Major bleeding occurred in 32 out of 522 patients on edoxaban, with 20 of the 32 (62.5%) requiring hospitalisation, whilst in the dalteparin group, 16 out of 524 patients experienced major bleeding, with 13 of the 16 (81.3%) requiring hospitalisation.

The number of patients needing admission to the intensive care unit was 18 (56.3%) in the edoxaban group vs. 12 (75%) in the dalteparin group. It was identified that no patients had more than one major bleed and that the additional instances of major bleeding with edoxaban were confined to patients with gastrointestinal cancer and predominantly occurred in the upper gastrointestinal tract. Major bleeding was classified according to the ISTH definition, though most events only required red blood cell transfusion. Among patients with nongastrointestinal cancer, the risk of major bleeding was comparable.

In patients with gastrointestinal cancer, the risk of bleeding in the edoxaban group was 12.7%, compared to 3.6% among those treated with dalteparin (HR:4; 95% CI, 1.5–10.6; p=0.005). The risk of severe major bleeding (ISTH category 3 or 4) in patients with gastrointestinal cancer was comparable between patients on edoxaban and dalteparin. There were no fatal bleeds among those treated with edoxaban versus two in the dalteparin group.

“We’ve seen previously that edoxaban offers an alternative to treatment with dalteparin for patients with cancerassociated VTE and these findings provide valuable clarity on its optimum use in patients with different types of cancer,” said Peter Verhamme, Department of Vascular Medicine and Hemostasis, University Hospitals Leuven, Leuven, Belgium. “It has been shown that for those with non-gastrointestinal cancer, the risk of major bleeding is comparable across

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patients treated with edoxaban versus dalteparin. While we are still investigating what specifically causes the higher risk of bleeding with edoxaban in gastrointestinal cancer patients, these data provide important insights that we need to weigh up in treatment decisions, considering the risk of recurrent VTE, patient preference regarding drug administration and the possible severity of bleeding.”

The Hokusai-VTE CANCER study was conducted in 1,050 patients with cancerassociated VTE, and included a broad spectrum of cancer patients, representative of those seen in clinical practice. Most patients had solid tumours originating from the gastrointestinal tract, lung or breast that were metastatic in over half of the cases at randomisation.

VTE is a common complication in cancer patients and is a leading cause of morbidity and mortality. It is estimated that 3–15% of patients with active cancer suffer from VTE, depending on cancer type, and that the prevalence of VTE in hospitalised patients is increasing. VTE can interrupt cancer treatment, which could have a negative impact on patient outcomes.

The new findings reported in Thrombosis and Haemostasis are further supported by a paper published in Expert Opinion on Pharmacotherapy, which reviewed expert opinion and guidance in cancer-associated thrombosis. The review noted that edoxaban is non-inferior to dalteparin, with a trend towards fewer recurrent VTE events, but with more major bleeding events. It was cited that similar findings to these were reported with rivaroxaban, though the study was not powered to allow definitive conclusions and no information was reported on concomitant cancer drugs.

Boston Scientific announces agreement to acquire Veniti

Boston Scientific has signed an agreement to acquire Veniti, a privately-held company in Fremont, USA which developed and commercialised the Vici venous stent system for treating venous obstructive disease.

Boston Scientific has been an investor in Veniti since 2016 and currently owns 25% of the company. The transaction price for the remaining stake consists of US$108 million up-front cash, as well as up to US$52 million in payments contingent upon US Food and Drug Administration (FDA) approval of the Vici stent system.

The self-expanding, nitinol Vici stent system was developed specifically for use in the venous anatomy, which presents different challenges than placing stents in the arterial vascular system. The Vici stent is designed to withstand compression and maintain patency and flexibility over the course of a patient’s life expectancy.

“This stent system was designed with the

Vici venous stent

distinctive demands of the venous system in mind, and built to provide physicians with a high-quality lumen across a variety of venous anatomies and disease states,” said Jeff Elkins, president and CEO of Veniti.

“We are excited to see this stent technology become even more accessible to physicians and the patients they treat under the leadership of Boston Scientific.”

The Vici stent system received CE mark in 2013 and Veniti submitted a pre-market approval (PMA) application to the FDA in June, leveraging results from the recently completed VIRTUS pivotal study. Currently in the USA, there are no stent technologies specifically indicated for use in the peripheral venous system.

“With the unique benefits of this differentiated technology and the strong experience of Boston Scientific in the overall venous market, we believe the Vici stent will become an important choice for physicians who choose stents to treat patients suffering from venous disease,” said Jeff Mirviss, senior vice president and president, Peripheral Interventions, Boston Scientific. “Along with our leading AngioJet thrombectomy platform and venous product pipeline, we look forward to meeting the needs of physicians treating both chronic and acute venous disease.”

The acquisition of Veniti is expected to be immaterial to Boston Scientific adjusted earnings per share (EPS) in 2018 and 2019, and accretive thereafter. On a GAAP basis for 2019 and subsequent years, the transaction is expected to be less accretive, or more dilutive as the case may be, due to amortisation expense and acquisition-related net charges. For 2018 on a GAAP basis, the transaction is expected to be accretive due to a one-time gain on prior investment. The completion of this transaction is imminent, subject to customary closing conditions.

In the USA, the Vici Stent System is an investigational device and is not available for sale.

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Product News EchoNous Vein receives FDA approval

EchoNous Vein (EchoNous), an ultrasoundbased tool designed specifically for nurses to improve peripheral IV catheter placements, has received US Food and Drug Administration (FDA) approval.

A company release explains that EchoNous Vein provides immediate, clear images at depths from 1–5cm for quickly visualising superficial and deeper veins with just two-button controls. EchoNous Vein will integrate with the company’s existing intelligent medical tool, Uscan, to form the EchoNous platform.

One of the most commonly performed minimally-invasive procedures, peripheral IVs can be challenging due to chronic illness, chemotherapy, obesity and drug abuse; first-attempt IV catheter insertion fails in up to 26% of adults and 54% of children.

“Time is critical, especially when patients need an infusion or antibiotic treatment, and finding the right vein can be challenging.

We designed the EchoNous Vein to provide nurses with rapid, clear images of veins to directly improve patient care, satisfaction and HCAHPS scores,” says Kevin Goodwin, CEO of EchoNous. “We wanted to create an easy-to-use tool that would help to reduce failed sticks, as with each failure comes a much higher risk of vessel trauma or infections which can lead to longer stays in hospital and higher medical costs.”

Early feedback from healthcare providers has shown the EchoNous Vein’s unique frequency profile and optimised gain and depth presets have the potential to provide significant advancements in evaluating veins of paediatric patients—a traditionally challenging patient population for IV insertion.

Mermaid Medical Group “EchoNous Vein’s simple on-screen acquires Angel Technology controls allows clinicians using ultrasound Mermaid Medical Group, a privately-owned to clearly identify veins in the centre of the international provider of minimally invasive display, helping to not just locate veins, medical devices, have announced the but to evaluate their health and quality acquisition of the Angel Catheter technology prior to peripheral IV placement,” says from Bio2 Medical.

Nancy Moureau, CEO of PICC Excellence.

The acquisition establishes Mermaid “As clinicians we know that IV insertion Medical’s presence in the vascular business, selecting a healthy vein for catheter adding a clinically proven and current placement can help to reduce the chance of commercialised product. The Angel post insertional complications. To have a tool catheter can minimise the incidence of specifically designed to easily select veins pulmonary embolism (PE) by utilising and guide catheter placement is extremely a “temporary” catheter with an attached valuable as we’re always looking to improve nitinol basket placed in the femoral vein. the patient experience.”

Bedside placement allows for easier, quicker, In addition to launching the new vascular placement while minimising hospital costs. access tool, the company also announces its The Angel catheter offers a safe, effective plan to converge its Signostics brand and AIalternative for catching potential thrombus driven Uscan bladder scanner product under due to trauma and various underlying patient the single EchoNous brand. disease states. The Angel catheter will be utilised throughout the hospital where NexGen Medical Systems patients are at risk of a pulmonary embolism. launches XCOIL large vessel Approved by the FDA in June 2015, thrombectomy system the Angel catheter became commercially NexGen Medical Systems., a US medical available in January 2017. The Mermaid device company, has announced the Medical Group will immediately begin successful completion of the first human supporting the current Angel customer base use of their XCOIL large vessel (18mm) worldwide, with plans to expand the product thrombectomy system for the treatment offering to additional existing Mermaid of deep vein thrombosis (DVT). The new Medical global markets. device, an expansion of the XCOIL 12mm

System, is designed to rapidly remove blood clots in large vessels, such as the iliac vein.

The company’s thrombectomy systems are comprised of an encapsulator sheath and a retractor catheter. The retractor is used to engage and extract the clot, pull it into the encapsulator and remove the clot from the body, while minimising the need for clotdissolving lytic drugs.

“This expansion of the XCOIL platform provides our customers with an effective portfolio of solutions for the many patients suffering from deep vein thrombosis in the USA,” said Denis Harrington, president and chief executive officer of NexGen Medical Systems. “With the successful addition of our large vessel solution, NexGen Medical continues to demonstrate our commitment to developing advanced solutions for treating DVT blood clots and in the future expanding our platforms to treat pulmonary embolism clots.”

David Buechner (Methodist Hospital, Memphis, USA), shared, “Our therapeutic goal is to rapidly restore blood flow by removing the clot, quickly and safely, while minimising the need for clotdissolving drugs which are not appropriate for all patients and can have negative side effects. The XCOIL thrombectomy system provides a rapid mechanical solution and may improve outcomes, and reduce costs, for our patients.”

The impact of blood clots can range from deep vein thrombosis to pulmonary embolisms and strokes. Blood clots account for more deaths each year than breast cancer, road traffic accidents, and AIDS combined.

Medical research committee gives approval for first-in-man VenoValve study

Hancock Jaffe Laboratories, a company specialising in bioprosthetic medical devices for treating cardiac and vascular diseases, has received approval for the first-in-man testing of its VenoValve bioprosthetic venous valve device from the Medical Research Committee at Fundación Santa Fe de Bogotá (FSFB), in Bogota, Colombia. The company previously received approval from the FSFB’s Ethics Committee.

Hancock Jaffe will now begin gathering the information necessary to submit an application for approval to Instituto Nacional de Vigilancia de Medicamentos y Alimentos (INVIMA), which is the Colombian equivalent of the US Food and Drug Administration. INVIMA approval is required to import investigational medical devices and conduct human clinical trials in Colombia.

Hancock Jaffe is developing the VenoValve to treat severe cases of chronic venous insufficiency. Approximately 4.5 million people in the USA suffer from severe chronic venous insufficiency, and the condition results from between 400,000 to 700,000 hospitalisations per year. There are currently no FDA approved treatments for deep venous chronic insufficiency.

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Events

Upcoming in the fall: Hands-on workshop of the European Venous Forum (EVF HOW) MARIANNE DE MAESENEER COMMENT & ANALYSIS

A colourful company

Since its foundation in 2000, the European Venous Forum (EVF) has taken the lead to develop all kinds of educational initiatives to share scientific knowledge, stimulate research and improve clinical practice, for the benefit of patients suffering from acute or chronic venous disease.

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ne of these important EVF initiatives has been the creation of the EVF Hands-On Workshop, known as the ‘EVF HOW’.

The first EVF HOW took place in 2010 in Larnaca, Cyprus under the lead of Andrew Nicolaides (Imperial College, London, UK), Bo Eklöf (University of Lund, Sweden) and Peter Neglén (Trimiklini, Limassol, Cyprus). After this first successful workshop it has been repeated annually at the end of October, and has been held in Vienna, Stockholm, Limassol and Krakow.

After the HOW in 2016, a new team of directors took over the torch: Stephen Black (Guy’s and St Thomas’, London, UK), Marianne De Maeseneer (Erasmus Medical Centre, Rotterdam, the Netherlands) and Tomasz Urbanek (Medical University of Silesia, Katowice, Poland)—always in close collaboration with Andrew Nicolaides.

A special course

The EVF HOW is a special course, combining theoretical didactic sessions, case management discussions, live demonstrations and, most importantly, hands-on training for modern phlebological procedures. Well-known Faculty members give ‘state-of-theart’ presentations about practical management of venous disease, in line with the most recently published guidelines. They discuss new insights and technical innovations, which can

(VIP), accessible with a designated password. There, participants can find all the presentations, didactic videos, case studies and interesting literature related to the HOW. They can access this website for up to one year after attending the EVF HOW.

be applied in daily practice. Fascinating cases are discussed with the audience.

For these case discussions, learners can also bring their own case. Often, together with the Faculty, potential solutions are found for an ‘unsolved’ problem of a patient back home. Obviously, the most important part of the EVF HOW is the hands-on training in the different workstations. In close collaboration with some of the most appreciated industrial partners, simulators and other didactic materials are used by the participants as if it were real-life circumstances. Duplex ultrasound is practised in patients with superficial or deep venous pathology, including transabdominal scanning, with tips and tricks on how to improve practical skills.

Privileges for the learners

Each workshop is limited to only 100 participants. There are 30–35 Faculty members­—resulting in a learner-tutor ratio of 3:1, which is quite unique, and allows a direct contact with the Faculty.

Even participants with a moderate knowledge of English, who may sometimes be afraid of asking questions in a general audience, can approach the tutors at low threshold. In this way, the impact of the EVF HOW on individual participants is significant. The learning experience is not limited to the course as such, but may be continued back home, when delegates can consult the Venous Interactive Portfolio

Participants and Faculty of the EVF HOW come from more than 25 countries from different continents, with a vast majority from Europe.

Last year the Polish delegates were the most numerous, and in 2016 the Portuguese. Most learners are vascular surgeons, followed by general surgeons, interventional radiologists, angiologists and dermatologists. Some would also categorise themselves as phlebologists, although this is not yet a separate specialty. This colourful mixture of delegates contributes to very lively discussions during the meeting—even continuing during the breaks, and

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sometimes with completely opposite opinions and interpretations.

Messages to take home

Every year, at the end of the course, the learners testify how important the experience has been for their daily practice and 97% state that they will change their practice, based on the different take-home messages and experience during the hands-on sessions.

The success of this course is mainly based on the enormous commitment of the Faculty members and the most valuable support of the EVF HOW industry partners. Thanks to the input of learners, Faculty and industry partners, the course improves every year, with a growing enthusiasm of all participants.

Marianne De Maeseneer is co-director of the EVF HOW. For more information about the EVF HOW 2018 (25–27 October, Limassol, Cyprus) and for registration visit the website: www.evfvip.com

Calendar of events 22–25 September

CIRSE: Cardiovascular and Interventional Radiological Society of Europe Annual Congress Lisbon, Portugal W cirse-2018.org 25–28 September

ESVS: European Society for Vascular Surgery Annual Meeting Valencia, Spain W esvs.org

27–29 September

SIR: ACTiVE (Advanced Therapies in Venous Interventions) Chicago, USA W sirweb.org 19 October

RSM thrombosis and anticoagulation conference London, UK W rsm.ac.uk 24–27 October

9th Annual EVF HOW Limassiol, Cyprus W evfvip.com

4–5 November

The VEINS Las Vegas, USA W vivaphysicians.org 8–11 November

ACP: American College of Phlebology annual meeting Nashville, USA W phlebology.org 23–24 November

EVF HOW Plus Venous Sclerotherapy & Phlebectomy Course Thun, Switzerland W evfvip.com

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