A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial.

Abstract

Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-2 was an open-label, pragmatic, multicentre, phase 3, randomised trial done at 41 vascular surgery units in the UK (n=39), Sweden (n=1), and Denmark (n=1). Eligible patients were those who presented to hospital-based vascular surgery units with chronic limb-threatening ischaemia due to atherosclerotic disease and who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Participants were randomly assigned (1:1) to receive either vein bypass (vein bypass group) or best endovascular treatment (best endovascular treatment group) as their first revascularisation procedure through a secure online randomisation system. Participants were excluded if they had ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease. Most vein bypasses used the great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug eluting stents. Participants were followed up for a minimum of 2 years. Data were collected locally at participating centres. In England, Wales, and Sweden, centralised databases were used to collect information on amputations and deaths. Data were analysed centrally at the Birmingham Clinical Trials Unit. The primary outcome was amputation-free survival defined as time to first major (above the ankle) amputation or death from any cause measured in the intention-to-treat population. Safety was assessed by monitoring serious adverse events up to 30-days after first revascularisation. The trial is registered with the ISRCTN registry, ISRCTN27728689. Findings: Between July 22, 2014, and Nov 30, 2020, 345 participants (65 [19%] women and 280 [81%] men median age 72�5 years [62�7-79�3]) with chronic limb-threatening ischaemia were enrolled in the trial and randomly assigned: 172 (50%) to the vein bypass group and 173 (50%) to the best endovascular treatment group. Major amputation or death occurred in 108 (63%) of 172 patients in the vein bypass group and 92 (53%) of 173 patients in the best endovascular treatment group (adjusted hazard ratio [HR] 1�35 [95% CI 1�02-1�80] p=0�037). 91 (53%) of 172 patients in the vein bypass group and 77 (45%) of 173 patients in the best endovascular treatment group died (adjusted HR 1�37 [95% CI 1�00-1�87]). In both groups the most common causes of morbidity and death, including that occurring within 30 days of their first revascularisation, were cardiovascular (61 deaths in the vein bypass group and 49 in the best endovascular treatment group) and respiratory events (25 deaths in the vein bypass group and 23 in the best endovascular treatment group number of cardiovascular and respiratory deaths were not mutually exclusive). Interpretation: In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy. Funding: UK National Institute of Health Research Health Technology Programme. Competing Interests: Declaration of interests AWB reports salary part paid by a National Institute for Health (NIHR) and Care Research Health Technology Assessment (HTA) BASIL-2 grant payment expert advice and testimony from NHS Resolution, His Majesty's Coroners, National Crime Agency, UK, Scotland, Wales, and Northern Ireland Governments, and various law firms, outside of the submitted work and payment to his institution and personal honoraria for committee work from NIHR HTA and NICE. GRB reports salary part paid by a NIHR HTA BASIL-2 grant the BASIL-2 grant also paid mileage for visiting patients in the BASIL-2 trial for follow-up assessments. AD reports honoraria from Boston Scientific, Cordis, Medalliance, and Abbott. KH reports honoraria from Le Maitre and Bayer. STR reports payment for expert testimony from McCollum Consultants consulting fees from 3M, Bayer, and Avita speaker fees from 3M, Bayer, Avita, and Terumo travel support Bayer and Terumo and is an advisory board member for 3M, Bayer, and Avita. AS reports honoraria and institutional grant support from Shockwave and Abbott and unpaid committee work for NICE. HZ reports an institutional grant from Abbott and honoraria from Limflow, Abbott, Boston Scientific, Bentley, Cook Medical, and Medtronic. All other authors declare no competing interests. Copyright 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.