Abstract

Objective 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 subgroup risk factor analysis. Data Sources MEDLINE, Embase, and Cochrane libraries. Review Methods This was a systematic review, meta-analysis, and time to event analysis of contemporary literature performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and registered with the International Prospective Register of Systematic Reviews (PROSPERO; ID: CRD42024497352). MEDLINE, Embase, and Cochrane libraries were searched on 2 December 2023, limited to 5 years and independently screened by two reviewers. All studies reporting mortality for patients undergoing major lower limb amputation for PAD or diabetes were included. Study quality and evidence certainty were evaluated via Risk of Bias 2, Newcastle–Ottawa, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) tools, respectively. 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. Results A total of 7 537 unique studies were screened, with 140 meeting criteria for inclusion. Short term mortality was estimated by weighted mean at 6.5% (range 1.8 – 34.1%) in hospital and 8.7% (0 – 26.8%) at 30 days (low GRADE certainty). Pooled time to event analysis was possible across 19 studies with 59 999 patients included. Estimated mortality was 28.9% at 1 year and 63.0% at 5 years with a median survival of 3.1 years (moderate GRADE certainty). Meta-analysed subgroup data demonstrated end stage renal disease, heart failure, frailty, and higher level amputation all increase mortality with peak odds ratios of 5.57, 2.14, 2.25, and 2.30, respectively. Diabetes was not associated with mortality. The time to event analysis for diabetes and level subgroups corroborated these results. 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. Conclusion Contemporary mortality 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.