CX to spotlight audience view on new BASIL-2 findings in headline peripheral session

providing a podium-first update on the trial and first-topodium quality-of-life data, respectively.

Unanswered questions

The results from BEST-CLI, a major multidisciplinary trial involving investigators from the fields of vascular surgery, interventional cardiology, interventional radiology and vascular medicine, were delivered at the American Heart Association (AHA) scientific sessions (5–7 November, Chicago, USA) and published simultaneously in the New England Journal of Medicine Since their release, the results have ignited debate over which patients are suitable for either an open surgical or endovascular approach.

Results of the trial showed that among a population of 1,830 CLTI patients deemed suitable either for an open or endovascular procedure, surgical bypass with adequate single-segment great saphenous vein (GSV) is a more effective approach. Both strategies, however, were shown to be safe and effective when it came to treating CLTI.

BEST-CLI co-principal investigators—Alik Farber, Matthew Menard, and Kenneth Rosenfield (Massachusetts General Hospital, Boston, USA)— acknowledge that the findings will provide important information regarding the management of CLTI patients. But, recent discussions of the trial’s results suggest that there is still some way to go to settle the question of which strategy should be favoured in patients suitable for either approach. This was brought to the fore in a standalone BEST-CLI session at the recent 2022 VEITHsymposium (15–19 November, New York, USA), which saw commentary being led by interventional cardiologist Eric Secemsky (Beth Israel Deaconess Medical Center, Boston, USA), representing a perspective from the endovascular community, and Michael Conte (University of California, San Francisco, San Francisco, USA), providing a view from the vascular surgery sphere.

Secemsky said BEST-CLI provided robust critical evidence but bore limitations in terms of the inclusion of major reintervention in the primary endpoint, the representativeness of non-surgical specialties in the trial, as well as the “generalisability” of the patients enrolled.

Conte said the trial showed that open surgery and endovascular intervention “are both safe and have complementary roles in the treatment of CLTI patients”. He said that open bypass with GSV provides more effective revascularisation in suitable candidates, and “is likely under-utilised in current practice,” adding that “an endo-first or endo-only approach to all patients with CLTI is not evidence-based care.” Centres carrying out less than 20% bypass in CLTI “should probably take stock,” he commented.

During the session, Farber delved into potential trial weaknesses. It was a pragmatically designed trial, with the possibility for selection and operator bias in enrolment and intervention, he noted. Farber also acknowledged the trial’s cohort 2 was likely underpowered. “The anatomical complexity is yet to be evaluated,” he added.

Rosenfield, meanwhile, noted the “controversy” the trial will generate: “[Amongst the BEST-CLI investigators] we have differences in the way we think it should be interpreted. My perspective is a little bit more muted than sort of the ‘Okay, this just tells the whole story about how you have to treat CLTI patients.’” His “top line,” he said, is that bypass fundamentally bears an important role in the treatment of CLTI, underscoring how the trial also showed that both procedures are safe. The lesser-discussed cohort 2, Rosenfield said, gets to one of his points of focus—that the study “raises a lot of questions that still need to be answered”.

The trial answers questions “about those patients n COMPLEX ANEURYSMS: n PERIPHERAL ARTERIAL DISEASE: n VENOUS STENTING: who were randomised in the trial,” he said, continuing, “We need to unpack better what were the characteristics of those patients who were entered into the trial.” That will help specialists determine the degree to which “we can generalise the findings: to which patients does this apply?”

Data from the UK-COMPASS trial provide new insights into the management of complex aneurysms in England and, according to lead investigator Srinivasa Rao Vallabhaneni (Liverpool, UK), underscore the need for appropriate patient and technique selection to avoid overtreatment.

For more on this story go to page 9.

Crossing chronic total occlusion lesions are challenging procedures. The BeBack crossing catheter—Bentley’s first product to be available in both Europe and the USA following the company’s acquisition of Upstream Peripheral Medical Technologies’ GoBack crossing catheter in September 2022— offers a new solution in this space. In a Bentleysponsored advertorial, Andrej Schmidt (Leipzig, Germany) shares his clinical experience with the BeBack, noting how it has been a “gamechanger” in his endovascular peripheral arterial disease practice.

For more on this story go to page 19.

Join the discussion

CX continues its three-year cycle of raising vascular and endovascular controversies in order to challenge the available evidence and to be able to reach a consensus after discussion with a global audience. Register for CX 2023 at www.cxsymposium.com to be one of the first to hear the latest data on revascularisation strategies in CLTI and be part of the data-driven discussion.

Prominent venous disease experts discuss venous stenting, appropriate care, and the quest to refine data and clinical practice in a space where part of the problem, one remarks, involves practitioners moving “freely from being able to do arterial intervention and suddenly assuming they can do a venous intervention”. For more on this story go to page 20.

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Age is just a number: Individual patient data metaanalysis probes safety of CEA in the elderly

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(1.94–2.14) in octogenarians, or 390 strokes in 19,101 patients, and 1.85% (1.75–1.95) in non-octogenarians, equating to 1.395 strokes in 75,537 patients (p=0.046).

In terms of perioperative death, the investigators report a figure of 1.09% (0.94–1.25) in octogenarians (203 strokes in 18,702 patients) and 0.53% (0.48–0.59) in non-octogenarians (392 strokes in 73,327 patients), with a p value of less than 0.0001.

The authors add that, per five-year age increment, a linear increase in perioperative stroke, MI, and death were observed (p=0.04–0.002). However, during the last three decades, they found that perioperative stroke and/or death has declined “significantly” in octogenarians, from 7.78% (5.58–10.55) before the year 2000 to 2.8% (2.56–3.04) after 2010, with a p value of less than 0.0001.

In the individual patient data multivariate analysis, which included 5,111 patients, age of 85 years or above was independently associated with perioperative stroke (p<0.001) and death (p=0.005). However, the investigators note that survival was similar for octogenarians vs. non-octogenarians at one year (95% [93.2–96.5] vs. 97.5% [96.4–98.6]; p=0.08), as was five-year stroke risk (11.93% [9.98 –14.16] vs. 12.78% [11.65–13.61]; p=0.24).

Leung, Howard and colleagues summarise that they found a “modest” increase in perioperative risk

And Treatment Of Carotid Atherosclerosis

A systematic review and metaanalysis has demonstrated “convincing evidence” that sex differences exist in carotid atherosclerosis, with all types of plaque features— including those relating to size, composition, and morphology—found to be either larger or more common in men than in women.

“Our results highlight that sex is an important variable to include in both study design and clinical decision-making,” the authors, led by Dianne van Dam-Nolen (Erasmus University Medical Center, Rotterdam, The Netherlands), write in the journal Stroke. “Further investigation of sex-specific stroke risks with regard to plaque composition is warranted.”

Over the past few decades, several individual studies on sex differences with age in symptomatic patients undergoing CEA. However, they stress that recurrent stroke risk also increases significantly with age when on medical therapy alone, and thus conclude that their findings “support selective urgent intervention in symptomatic elderly patients”.

In the discussion of their findings, Leung, Howard et al claim that theirs is the first meta-analysis of CEA safety by age for patients with symptomatic carotid disease, which includes all study types and individual patient-level data analysis. The study is also novel in its findings, the authors note, writing that “although symptom status is known to be strongly associated with recurrent stroke risk and post-CEA morbidity, this is the first study to confirm the association of age with both short- and long-term outcomes in symptomatic patients”.

The investigators state that their findings have several implications for clinical practice. For example, they highlight the finding that the effect of age on perioperative morbidity was linear without a clear step-change in risk, which “contrasts with the current notion of higher perioperative morbidity in the elderly once they reach a certain age”.

They also address implications around the “major concern” of cardiac risk for elderly patients undergoing intervention. As well as confirming a modest linear increase in perioperative cardiac risk with age, pooled estimates revealed a higher annual stroke or death rate in the elderly compared to younger patients when stratified by prevalence of known coronary artery disease. “This key finding supports clinical caution in selecting elderly patients in carotid atherosclerosis have been performed, covering a wide range of plaque characteristics and including different populations, the authors state.

In addition to summarising previously reported results on sex differences in this space, the researchers also sought to “present a roadmap explaining next steps needed for implementing this knowledge in clinical practice”.

They began by systematically searching PubMed, Embase, Web of Science, Cochrane Central and Google Scholar for eligible studies, including both male and female participants, and reporting the prevalence of imaging characteristics of carotid atherosclerosis. The eligible studies were then meta-analysed. Van DamNolen et al prespecified which imaging modalities had to be used per plaque characteristic and excluded ultrasonography.

After initially identifying more than 1,000 unique citations, screening of the articles based on the inclusion criteria whittled this number down to a total of 60 articles, with 42 being included in the final meta-analyses.

Six of these studies were included in a meta-analysis on the relationship between sex and atherosclerotic plaque size. All three of the characteristics used to measure plaque with significant coronary artery disease for CEA. Conversely, it also provides reassurance that for elderly patients without major cardiac comorbidity, outcome following CEA is similar to that of younger patients,” the authors detail.

The authors also acknowledge some limitations of their study. These include the fact that patients in studies published before 2010 may not have been on contemporary intensive medical therapy for control of vascular risk factors, which “may contribute to an overall higher risk of stroke and death than that found in current clinical practice”. To account for this, the investigators relay that their time-trend analyses have confirmed reductions in risk following surgery over the last three decades.

Looking ahead, Leung, Howard et al consider what future research might be of benefit in this space: “Future clinical trials investigating the efficacy of surgery versus best medical therapy alone for very elderly symptomatic patients would be of clinical interest.” size—maximum wall thickness (1D size), wall area (2D size), and wall volume (3D size)—were more likely to be larger in men than in women, van Dam-Nolen et al report. However, conversely, the normalised wall index, which accounts for the total vessel size, did not statistically significantly differ between male and female participants, which the researchers describe as “surprising”, and possibly indicative of sex differences in plaque size being driven by contrasting vessel sizes.

However, they recognise that eliminating selective recruitment bias in such trials “would be very challenging” and thus “interpreting results would require great caution”.

In addition, analysing three of the studies further regarding the degree of stenosis, the authors found no statistically significant sex difference for stenosis of 50–69%, although highgrade stenosis of 70–99% was more often seen in men than in women.

Meta-analyses relating to plaque composition examined the presence of calcifications, lipid-rich necrotic core (LRNC), and intraplaque haemorrhage (IPH), and found a higher prevalence in men versus women across all three components. Expounding briefly on their calcification findings, van Dam-Nolen et al report statistically significant differences between men and women for the presence and amount of carotid calcifications, but not in terms of calcification percentage i.e. the amount of calcification relative to the total plaque volume.

“Furthermore, we found more pronounced sex differences for LRNC in symptomatic as opposed to asymptomatic participants,” they add. Five studies were also included in the meta-analysis of the relationship between sex and plaque morphology, with the presence of ulceration and the presence of a thin-or-ruptured fibrous cap both being higher in men.

In their report, the authors highlight multiple limitations of their analysis that “deserve comment”, including moderate-to-high heterogeneity among the included studies—especially with regard to plaque size and carotid calcifications—as well as the fact it was not possible to adjust for potential confounders on the relationship between sex and carotid atherosclerosis.

“The found sex differences in carotid atherosclerosis are of clinically significant importance, since the composition of plaque affects the risk of (recurrent) stroke,” van Dam-Nolen et al conclude. “Previous studies have shown that especially IPH contributes to a higher stroke risk. Carotid LRNC, calcifications, total plaque size, and plaque ulceration, have also been reported as important risk factors. With regard to sex-specific risk prediction and treatment, it is essential to investigate the effect of these plaque characteristics per sex separately. We hypothesise that the stroke risk as a result of specific plaque compositions varies among men and women.”