Editor's Choice - Systematic Review, Meta-analysis, and Time to Event Analysis of Contemporary Mortality after Major Lower Limb Amputation for Peripheral Arterial Disease or Diabetes Mellitus.

Abstract

Major lower limb amputation for peripheral arterial disease (PAD) or diabetes mellitus carries high mortality risk. This time to event and meta-analysis reports contemporary survival and risk factor analysis. MEDLINE, Embase, and Cochrane libraries. Systematic review, meta-analysis, and time to event analysis were undertaken. The literature was searched on 2 December 2023, limited to five years. All studies reporting death for patients undergoing major lower limb amputation for PAD or diabetes were included. Evidence certainty was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tool. Mean values weighted by study size were used for short term mortality estimation, pooled time to event survival analysis for mid to long term, and random effects modelling for subgroup meta-analysis. A total of 7 537 unique studies were screened, with 140 meeting criteria for inclusion. The in-hospital mortality rate was 6.5% (range 1.8 - 34.1%), reaching 8.7% (0 - 26.8%) at 30 days (low GRADE certainty). Time to event analysis was possible across 19 studies inclusive of 59 999 patients. Estimated mortality was 28.9% at one year, 63.0% at five years, with a median survival of 3.1 years (moderate GRADE certainty). End stage renal disease, heart failure, frailty, and higher-level amputation were all associated with increased mortality, demonstrating peak odds ratios of 5.57, 2.14, 2.25, and 2.30, respectively. Diabetes was not associated with mortality. Median survival for patients with diabetes was 2.7 years (95% confidence interval 2.0 - 3.5 years) compared with 3.1 years (1.9 - 4.7 years) for those with PAD alone. Subgroup analyses were of very low to moderate GRADE certainty. Contemporary mortality rates after major lower limb amputation for PAD or diabetes remains high. End stage renal disease, heart failure, frailty, and higher level of amputation were all associated with mortality risk.