Introduction and experimental set-up
The choice of which method of revascularization to use in chronic limb-threatening ischemia (CLTI) is still controversial in 2022. BEST-CLI is an international, prospective, randomized, open-label, multi-center, superiority trial. Patients were enrolled at 150 sites in the United States, Canada, Finland, Italy, and New Zealand. The trial consisted of two parallel studies that were based on a preprocedural assessment of the availability of autogenous conduit for vein bypass: either a single segment of the great saphenous vein (cohort 1) or the need for an alternative bypass conduit (cohort 2). Patients were enrolled into one of two parallel trial cohorts according to prerandomisation duplex ultrasonography of the right and left great saphenous veins. Enrollment began in August 2014 and continued through October 2019. The patients in cohort 1 were followed through October 2021, and those in cohort 2 were followed through December 2019.
Eligible patients were at least 18 years old and had received a diagnosis of 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 as follows:
- Ischemic rest pain alone (Rutherford class 4) defined as ankle systolic pressure < 50 mm Hg, toe pressure of < 30 mm Hg, transcutaneous PO2 of < 30 mm Hg, or flat-line transtarsal pulse volume recording.
- Tissue loss with or without ischemic rest pain (Rutherford class 5, 6) defined as ankle systolic pressure < 70 mm Hg, toe pressure of < 50 mm Hg, transcutaneous PO2 of < 30 mm Hg, or flatline transtarsal pulse volume recording
The primary outcome was a composite of major adverse limb events or death from any cause. A major adverse limb event was defined as above the ankle amputation of the index limb or a major index-limb reintervention (new bypass, interposition graft revision, thrombectomy, or thrombolysis).
1434 patients with a single segment of great saphenous vein underwent randomization in cohort 1 (718 to receive surgical treatment and 716 to receive endovascular therapy) and were followed for up to 7 years, with a median follow-up of 2.7 years. Procedures that were performed in the surgical group included 307 femoral–popliteal, 276 femoral–tibial or pedal, and 115 popliteal–tibial or pedal bypass operations; 85% of the procedures were performed with a single segment of the great saphenous vein.
396 patients without a single segment of great saphenous vein underwent randomisation in cohort 2 (197 to receive surgical treatment and 199 to receive endovascular therapy) and were followed for a median of 1.6 years.
The incidence of a major adverse limb event (major amputation or reintervention in the index limb) or death from any cause (the primary composite outcome) was lower in the surgical group than in the endovascular-therapy group (42.6% vs. 57.4%) in cohort 1 (hazard ratio, 0.68; 95% CI, 0.59 to 0.79). The incidence of primary outcome was not different between the surgical group and the endovascular group difference (42.8% vs. 47.7%) (hazard ratio, 0.79; 95% CI, 0.58 to 1.06). In cohort 1, the more favorable primary outcome in the surgery group was mainly driven by the lower risk of major reintervention with a hazard ratio of 0.35 (95% CI, 0.27 to 0.47) and the risk of above-ankle amputation with a hazard ratio of 0.73 (95% CI, 0.54 to 0.98). Below-the-knee revascularisations followed the same results.
The BEST-CLI trial is a well-designed, well-conducted trial that provides strong evidence in favor of using surgical revascularisation when saphenous vein material is available to treat chronic limb-threatening ischemia. This strategy reduces the risk of reintervention and major amputation. In other cases, the endovascular approach or bypass surgery may be proposed univocally.