High rates of nonindex limb amputation in the Best Endovascular versus Best Surgical Therapy in Patients with Critical Limb Ischemia (BEST-CLI) trial.

OBJECTIVE: To evaluate the incidence and risk factors associated with nonindex limb (NIL) above-ankle amputations among BEST-CLI (Best Endovascular vs Best Surgical Therapy in Patients with Critical Limb Ischemia) trial participants. BACKGROUND: BEST-CLI compared endovascular therapy and infrainguinal bypass for patients with chronic limb-threatening ischemia (CLTI), focusing on the ipsilateral index limb. However, it is recognized that peripheral artery disease (PAD) can also impact the contralateral limb. We sought to evaluate the incidence and risk factors associated with NIL above-ankle amputations among BEST-CLI trial participants. METHODS: We analyzed data from 1400 participants in BEST-CLI. The primary outcome was the occurrence of above-ankle amputation in the NIL. Secondary outcomes included revascularization in the NIL, above-ankle amputation in the index limb, and mortality at the 3-year follow-up for the cohort that underwent NIL above-ankle amputations. Multivariable Cox regression was used to identify factors associated with above-ankle amputation in the NIL. RESULTS: Ninety-six participants (6.9%) underwent a NIL above-ankle amputation over the course of follow-up. These patients were more likely to be younger at enrollment (63 vs 67 years; P < .001), have diabetes mellitus (81.3% vs 66.1%; P = .002), end-stage renal disease (ESRD) (28.1% vs 9.0%; P < .001), and lower NIL toe pressure at enrollment (52 ± 31.6 mm Hg vs 64 ± 32.2 mm Hg; P = .015). Participants who underwent NIL amputation had significantly higher rates of open or endovascular revascularization in NIL (90.6% vs 17.7%; hazard ratio [HR], 10.95; 95% CI, 8.56-14.01; P < .001) and above-ankle amputations in the index limb (45.8% vs 12.1%; HR, 4.62; 95% CI, 3.28-6.50; P < .001). On 3-year Kaplan-Meier analysis, there was no significant difference in all-cause mortality between participants with and without NIL amputations (26.2% vs 28.2%; HR, 1.28; 95% CI, 0.92-1.77; P = .15). In multivariable Cox regression, NIL above-ankle amputation was associated with younger age at baseline (HR, 0.94; 95% CI, 0.89-1.00; P = .047), ESRD (HR, 10.73; 95% CI, 3.09-37.30; P < .001), and lower NIL toe pressure at baseline (HR, 0.98; 95% CI, 0.97-1.00; P = .049). CONCLUSIONS: In the BEST-CLI trial cohort, NIL above-ankle amputations were associated with ESRD, lower NIL toe pressure, and younger age. A significant proportion of patients who had a NIL above-ankle amputation also underwent revascularization of NIL and an index limb above-ankle amputation within 3 years. Our findings highlight the need for targeted preventive strategies that focus on both limbs in high-risk populations to enhance limb preservation after revascularization for peripheral artery disease.