A dedicated session at the 2023 VEITHsymposium (14–18 November, New York, USA) aimed to unpack the ways in which clinical practice and attitudes in the field of chronic limb-threatening ischaemia (CLTI) have changed since the BEST-CLI trial was published back in November 2022. The trial’s principal investigators (PIs)—vascular surgeons Alik Farber and Matthew Menard and interventional cardiologist Kenneth Rosenfield (all Boston, USA)—invited a multidisciplinary panel of opinion leaders from both the USA and Europe to share their thoughts and highlight some unanswered questions.
“We don’t cure these people”
First to comment was vascular surgeon Peter Schneider (University of California San Francisco, San Francisco, USA). “One thing I think is worth calling out is the change over one year,” he began. Schneider recalled that, during a 2022 VEITHsymposium session on BEST-CLI, “everybody was worried in some way” about what was going to happen next. A year later, “that’s melted away completely”. This change, in Schneider’s view, is testament to the leadership of the three PIs.
Schneider’s main point was that BEST-CLI has contributed to a recognition that CLTI treatment is “much more complicated” than revascularisation alone, predicting that the field is “going to become more like cancer treatment”. He continued: “These people have cancer. It was clear to all of us how sick they are, but now it will be clear to a much broader audience.”
Vascular surgeon Joseph Mills (Baylor College of Medicine, Houston, USA), current president of the Society for Vascular Surgery (SVS), expanded on Schneider’s point. “This cancer analogy works really well,” he said. “We don’t cure these people, and what we want to do is try to put them in remission for as long as possible.” Mills advocated the use of endpoints that look at disease-free survival and wound-free period, highlighting their utility in assessing long-term outcomes. “We should start looking at what’s better for [patients’] long-term care and not even one- or two-year results, but what happens over the lifespan of that patient,” he said.
Antiproliferative therapy is key
Interventional radiologist Robert Lookstein (Icahn School of Medicine at Mount Sinai, New York, USA) also commented, first echoing Schneider’s sentiment that “the discourse [around BEST-CLI] has become more constructive than deconstructive” over the course of the past 12 months, in large part thanks to the PIs’ leadership.
He was keen to stress, however, that it is “obviously concerning” BEST-CLI reached different outcomes to BASIL-2—presented in April 2023. “It should be recognised that these trials were designed to study different populations,” he noted. Lookstein also highlighted the fact that there were very few women and underrepresented minorities enrolled in these two trials and cautioned extrapolating the trial results to these specific demographics.
Lookstein’s main point had to do with the importance of antiproliferative therapy. He referenced a retrospective analysis presented earlier in the session by vascular surgeon Michael Conte (University of California San Francisco, San Francisco, USA) that suggested the best results for freedom from reintervention in the endovascular arm of BEST-CLI were seen in those patients treated with drug-coated balloons and stents. Lookstein stated “the endovascular arm would probably have had better outcomes” had the endovascular protocol been standardised with the use of antiproliferative therapy in the infrainguinal circulation. “We have massive amounts of data [showing] that [antiproliferative therapy] is superior to non-antiproliferative therapy,” he stressed, asking why—against this backdrop of evidence—any vascular specialist would withhold this technology from their patients.
In response to this point, Rosenfield, of Massachusetts General Hospital, pointed out that if he were to place a bare metal stent in a coronary vessel, “that would almost be malpractice”.
Menard, of Brigham and Women’s Hospital, highlighted that one of the very important current challenges is that of “how to get the best endo[vascular] and the best surgery out there”.
Lookstein shared his opinion on this: “I think it behooves all of us to either lobby the guidelines or to speak out.” He mentioned again the “profound” data presented by Conte and posited, “I firmly believe that drug-coated balloons and stents must be considered the standard of care at this point.”
Put the patient first
Vascular surgeon Elizabeth Genovese (Penn Medicine, Philadelphia, USA) noted the endovascular-first nature of her clinical expertise, which stemmed from the fact that she had worked for five years in the south east of the USA where her patients had been “very medically complex and often poor surgical candidates”.
Once BEST-CLI was published, Genovese stated that she moved to offering a more “patient-first” approach. Now, she relayed, her practice is framed around the question of which patients fall into the BEST-CLI cohort that does well with bypass first compared to an endovascular-first approach. “These are the patients who not only have good vein, but that tend to be on the healthier spectrum of the patient population; these are the patients that I didn’t necessarily see in the first five years of my practice,” Genovese noted. “But simultaneously, the patients in the open cohort had a fairly high anatomic complexity,” she added, referencing that over 60% of patients had infrapopliteal targets and 51% of the endovascular arm required tibial interventions.
“[This study has] made us realise that in the right patient population, in more complex anatomic patients, bypass first remains still a really good and durable option,” Genovese summarised.
No more silos
Interventional cardiologist Carlos Mena-Hurtado (Yale School of Medicine, New Haven, USA) also shared his thoughts on BEST-CLI, remarking that—at least in his opinion and at his institution—the trial was “incredibly important”. He elaborated: “It made us come out of silos and it made us understand that CLTI is more than simply just revascularisation.” Mena-Hurtado stressed that, while there is “a lot of work to do,” it is important not to put blame on each other. “I think we need to create the spaces where we can come together and discuss how best to [treat these patients],” he commented.
“The single most important thing that I learnt from the trial was the fact that when we had a patient with CLTI come into our facility, we would be forced to look at [the case] together,” Mena-Hurtado said in summary. “We continue that practice up until today and I think it has made not only our outcomes better but our patients better.”
More work to be done
Vascular surgeon Maarit Venermo (Helsinki University Hospital, Helsinki, Finland)—who noted that her centre was the first site outside the USA to join the BEST-CLI trial—made a point about what is next in terms of research in this space. She referenced the “huge number” of future studies that are in the works, which she believes will inform decisions around which treatment is best for which subgroups of CLTI patients. “Also, there will be a population who don’t benefit from endo[vascular] or open surgery,” she added, stressing the importance of taking this into account when making clinical decisions.
Farber, of Boston Medical Center, also encouraged audience members to look ahead to what is next, stressing that BEST-CLI and BASIL-2 are just the start. “No matter what your views are on [BEST-CLI] or BASIL-2, the exciting thing is that we have data coming in this space, which did not have a lot of data [before],” he shared, emphasising, however, that “there’s more work that needs to be done”. To this end, Farber highlighted that the “top priority” now is to “harmonise” BEST-CLI and BASIL-2 using patient-level data. “It’s an exciting time,” he summarised.
Excellent review