The BEST-CLI (Best Endovascular Versus Best Surgical Therapy in Patients With CLTI) and BASIL-2 (Bypass versus Angioplasty for Severe Ischemia of the Leg-2) trial results provide insight into revascularization strategies among patients with chronic limb threatening ischemia (CLTI), which was defined as arterial insufficiency of the lower limb with ischemic foot pain at rest, a nonhealing ischemic ulcer, or gangrene, as corroborated by hemodynamic criteria.^1,2 This expert analysis discusses both trials' results and highlights the important takeaway points for clinicians.

The BEST-CLI trial compared surgical bypass revascularization with great saphenous vein (GSV) conduit to endovascular treatment. The primary outcome was a composite of major adverse limb events (MALE; i.e., above-ankle amputation or index-limb reintervention) or all-cause mortality. The investigators enrolled 1,830 patients with CLTI from the United States, Canada, Finland, Italy, and New Zealand between August 2014 and October 2019, of whom 1,434 had a suitable GSV (cohort 1) and 396 needed an alternative conduit (cohort 2). Of the 1,434 patients in cohort 1, 718 were randomly assigned to the surgical-treatment group and 716 to the endovascular-treatment group. Of the 396 patients in cohort 2, 197 were randomized to the surgical-treatment group and 199 to the endovascular-treatment group.

In cohort 1, after a median follow-up of 2.7 years, the primary outcome for bypass surgery was 42.6% and for endovascular therapy was 57.4% (hazard ratio [HR] 0.68; 95% confidence interval [CI], 0.59-0.79; p < 0.001), driven mainly by index-limb reintervention. In cohort 2, the primary outcome for bypass surgery was 42.8% and for endovascular therapy was 47.7% (HR, 0.79; 95% CI, 0.58-1.06; p = 0.12).

The outcomes of the BEST-CLI trial reveal that, among patients with CLTI for whom both surgical and endovascular interventions are feasible, surgery with the GSV conduit is superior to endovascular intervention; however, when the GSV conduit is not available, outcomes between surgery and endovascular intervention are similar. Improvement in health-related quality of life was more often found in patients who underwent endovascular intervention. Death from any cause was similar between surgery and endovascular intervention: 234 (33%) patients in the bypass-surgery group and 267 (37.6%) patients in the endovascular-treatment group (HR, 0.98; 95% CI, 0.82-1.17).

The BASIL-2 trial also compared surgical revascularization with endovascular therapy. Randomization included stratification by clinical presentation (Rutherford-Becker category 4 vs. 5/6) and the presence versus absence of significant infrapopliteal disease. The investigators recruited patients with CLTI from the United Kingdom, Denmark, and Sweden between July 2014 and November 2020. The trial population included 345 patients with CLTI (19% women, median age 72.5 years [interquartile range, 62.7-79.3]). The patients were randomized into two groups: 172 to the vein-bypass group and 173 to the endovascular-treatment group. The primary outcome was amputation-free survival defined as time to major (above-ankle) amputation or death from any cause. Secondary outcomes included MALE, defined as major amputation of the trial leg or any additional major reintervention to the trial leg. The median follow-up period for the participants was 2 years.

In the vein-bypass group, there was major amputation or death in 108 (63%) patients and, in the endovascular-treatment group, there was major amputation or death in 92 (53%) patients (adjusted HR, 1.35; 95% CI, 1.02-1.8; p = 0.037). MALE occurred in 71 (41%) patients in the vein-bypass group and in 77 (45%) patients in the endovascular-treatment group (adjusted HR, 0.93; 95% CI, 0.67-1.29). The outcomes of the BASIL-2 trial revealed that, among patients with CLI due to infrapopliteal disease, endovascular treatment was superior to vein bypass in reduction of death or major amputations. Death from any cause was similar between surgery and endovascular intervention: 91 (53%) patients in the vein-bypass group and 77 (45%) patients in the endovascular-treatment group (HR, 1.37; 95% CI, 1-1.87).

Although seemingly contrasting conclusions, the results of these two trials highlight different aspects of presentation and care in patients with CLTI. The location of the lesions that were intervened upon differed between both trials, as the BEST-CLI trial included patients undergoing infrainguinal revascularization intervention and the BASIL-2 trial included patients who were undergoing infrapopliteal revascularization. Both trials' results showed that patients with CLTI have high mortality rates regardless of the intervention procedure: death occurred in 35% of patients in cohort 1 of the BEST-CLI trial, in 25% in cohort 2 of the BEST-CLI trial, and in 49% in the BASIL-2 trial.

Both trials had important limitations. More than 70% of the patient population in both trials was men. In the BEST-CLI trial, approximately 70% of the patient population was white and, in the BASIL-2 trial, 91% of the patient population was white. Hence, the results of the two trials do not apply to all patients with CLTI because of the poor representation of women and people of races other than white. Additionally, in both trials, patients who were included had to have good veins and be good surgical candidates, which again further limited the full spectrum of CLTI patient representation. The results of both trials showed that 20-30% of the patients with CLTI were not taking optimal medical therapy, as 25-40% of patients were not taking antiplatelet or lipid-lowering therapy.

Overall, the results of both the BEST-CLI and the BASIL-2 trials advance the management of peripheral artery disease, aiming to reduce amputation and reintervention. The high rates of mortality among both trial populations stress the need for optimizing preventive medical therapy focused on reducing atherosclerotic disease progression whenever possible.

References

1. Farber A, Menard MT, Conte MS, et al.; BEST-CLI Investigators. Surgery or endovascular therapy for chronic limb-threatening ischemia. N Engl J Med 2022;387:2305-16.
2. Bradbury AW, Moakes CA, Popplewell M, et al.; BASIL-2 Investigators. 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. Lancet 2023;401:1798-809.