Data and discussion on revascularisation treatment strategies for patients with chronic limb-threatening ischaemia (CLTI) will take centre stage at the CX 2023 Consensus update, with results from the BASIL-2 (Bypass versus angioplasty in severe ischaemia of the leg-2) randomised controlled trial (RCT) to be presented for the first time. Chief investigator Andrew Bradbury (University of Birmingham, Birmingham, UK) speaks to Interventional News about the background, context and significance of the trial ahead of this year’s meeting.
Bradbury notes that BASIL-2 has its origins in the original BASIL-1 trial, the short-term results of which were published in The Lancet in 2005. BASIL-1 randomised (1999–2003) patients with severe limb ischaemia, mainly due to femoropopliteal disease, to either a plain balloon angioplasty-first or a bypass surgery-first revascularisation strategy. With “fairly limited follow-up,” Bradbury recalls, there did not seem to be much of a difference in the primary outcome of amputation-free survival. There was, however, a suggestion that the data from both groups were “beginning to diverge,” which prompted the team to follow the patients up for longer. Reporting the key finding from these later outcomes, Bradbury summarises that “people randomised in BASIL-1, and who were likely to live for more than two years, and who had a good vein, were best served by having a vein bypass first rather than a plain balloon angioplasty first”.
Speaking on his motivation for starting the BASIL-2 trial, Bradbury recollects how it became clear there were a number of gaps in peripheral arterial disease (PAD) research during his involvement in the UK National Institute for Health and Care Excellence (NICE) guideline expert group on PAD. One such gap had to do with infrapopliteal, or below-the-knee, disease, and Bradbury notes that NICE made a research recommendation to undertake a randomised controlled trial compare a ‘vein bypass-first’ with a ‘best endovascular treatment-first’ strategy for people who required an infrapopliteal procedure. This is what BASIL-2 endeavoured to achieve.
“Endovascular techniques and technologies for lower limb revascularisation are very different now from what they were 15–20 years ago when we did BASIL-1,” Bradbury remarks, noting for example better guidewires, better balloons, more skilful entry and retrograde cannulation to name just a few developments. As a result, the team are keen to see how the two treatment modalities compare in this new treatment landscape.
In addition, the question at the centre of BASIL-2 represents a “massive global problem” and therefore an important one to solve, Bradbury comments. He elaborates: “I have had the opportunity to visit hospitals in many different countries, and vascular wards wherever you go are essentially full of people with CLTI.” Bradbury explains that BASIL-2 is his and his team’s “attempted contribution” to try and improve the evidence base for the treatment of these patients who are “very challenging” and often “very poorly,” with multiple comorbidities.
BASIL-2 is a superiority trial, Bradbury explains, noting that the hypothesis the investigators started with was that vein bypass would be superior due to the fact that BASIL-1 “seemed to show that vein bypass had advantages over endovascular intervention”. He adds that it is a pragmatic trial, and thus surgeons and interventional radiologists are permitted to use their preferred techniques and equipment, with the primary outcome being amputation-free survival (time to major—above the ankle—amputation, or death from any cause, whichever occurs first).
Considering the BASIL-2 trial in its wider context of randomised data in this space, Bradbury notes that the investigators have been in “friendly dialogue” with the BEST-CLI team “from the get-go”. Results of the BEST-CLI trial were presented late last year, with the headline finding being that surgical bypass with adequate single-segment great saphenous vein is a more effective revascularisation strategy for patients with CLTI who are deemed to be suitable for either an open or endovascular approach.
Bradbury notes that there are a number of differences between the two trials, highlighting for example that BASIL-2 included a different group of patients. “Only about 40% of [BEST-CLI] patients has a below-the-knee intervention,” he says. “We are focused in BASIL-2 on below the knee, and [BEST-CLI] did not pre-specify an only below-the-knee analysis.” While BEST-CLI is “not exclusively a femoropopliteal trial,” it has similarities to BASIL-1 in that it is more of a femoropopliteal trial with or without infrapopliteal disease, whereas BASIL-2 is specifically looking at infrapopliteal revascularisation, Bradbury explains.
BASIL-2 and BEST-CLI are both RCTs, however Bradbury is keen to stress the limitations of this high level of evidence. “An RCT is not a GPS, it is more like a wobbly compass near the North Pole, and all it can try and do is push you in a certain direction of travel,” he comments. He adds that while both the BASIL-2 and BEST-CLI teams are “huge enthusiasts” for RCTs, this type of research must still be scrutinised.
Looking ahead to CX, Bradbury expresses his excitement at the prospect of presenting the BASIL-2 data for the first time at what he describes as “the big UK vascular and endovascular meeting”. “I am really looking forward to seeing everyone at CX 2023 and it is going to be a great meeting. It is a pleasure and a privilege for us to be part of it and have the opportunity to present our trial data for the first time.”
Bradbury hopes that once the audience hear the results, as well as the limitations, which “every RCT has,” they will “go away and reflect” on the data and think about them “in the context of their own practice, their own healthcare system and come to a decision as to whether these new data are going to influence their practice, or not, as the case may be”.
Ultimately, Bradbury believes, CLTI treatment “is all about team-working” to determine what is best for the patient. “We sit in an MDT [multidisciplinary team meeting] and there is a discussion about a leg and whether we are going to do endo or vein bypass. It does not necessarily mean the same person has to do both procedures, and I think that is a positive. I do not think people see that as a threat […] and I think most people would think it was better for the patient.”
Join the conversation at CX 2023
During the CX session, Bradbury will deliver the results of the BASIL-2 trial, with co-investigators Catherine Moakes, Gareth Bate and Matthew Popplewell (all University of Birmingham, Birmingham, UK) and Lewis Meecham (University Hospital Cardiff, Wales), set to present on the journey from BASIL-1 to BASIL-2, methodology, study limitations and future work, among other topics.
Attendees in London and remote participants will have the opportunity to pose questions to the BASIL-2 investigators, who—along with an expert panel and in the presence of the US Food and Drug Administration (FDA) and Secretary of State for Health—will interrogate the evidence in a roundtable discussion to reach consensus on this hotly debated topic.
You can watch the BASIL-2 Podium First presentation 11:10–11:40 on Tuesday 25th April and the roundtable discussion 12:00–13:00.