Frailty and the efficacy and safety of surgical versus endovascular revascularization: post-hoc analysis of the BEST-CLI trial

BACKGROUND: Frailty is associated with mortality and adverse outcomes in chronic limb-threatening ischaemia (CLTI). Although prompt revascularization is recommended to reduce major adverse limb events (MALE), it is unclear whether frailty modifies the relative effectiveness of surgical versus endovascular therapy. The aim of this study was to assess whether the outcomes of these strategies differ by frailty status in the BEST-CLI randomized trial. METHODS: A frailty index (FI; 0-1) was constructed using a deficit-accumulation approach; severe frailty was defined as an FI ≥0.45. The primary endpoint was MALE or death, and the safety endpoint was major adverse cardiovascular events (MACE). Patients with an adequate great saphenous vein (GSV) (cohort 1) and those requiring an alternative conduit (cohort 2) were analysed separately. RESULTS: Of 1830 randomized patients, the FI was calculable for 1754 patients. Severe frailty was present in 654 patients (47.6%) in cohort 1 and 187 patients (49.3%) in cohort 2 and was associated with higher MALE or death regardless of treatment. In cohort 1, surgical bypass reduced the risk of MALE or death in both severely frail patients (51.0% versus 67.2%; HR 0.68 (95% c.i. 0.55 to 0.83)) and non-severely frail patients (35.4% versus 48.2%; HR 0.68 (95% c.i. 0.54 to 0.86)) versus endovascular therapy (interaction P = 0.95). In cohort 2, outcomes were similar between treatment groups across frailty strata. No interaction was observed between frailty and treatment strategy for MACE. CONCLUSION: In the BEST-CLI trial, severe frailty was associated with higher MALE or death. Among patients suitable for bypass with an adequate GSV, surgical bypass was more effective than endovascular therapy irrespective of frailty status.