Frailty and Adverse Outcomes After Endovascular Revascularization for Chronic Limb-Threatening Ischemia: A Systematic Review and Exploratory Meta-Analysis

Abstract

Frailty is an increasingly recognized prognostic construct in patients with chronic limb-threatening ischemia (CLTI), but its association with adverse outcomes specifically after endovascular revascularization is uncertain. This systematic review and meta-analysis synthesized observational prognostic evidence linking frailty to post-revascularization outcomes in this population. Observational prognostic studies reporting endovascular-specific, frailty-stratified effect estimates in adults with CLTI were included. Frailty was defined using study-specified instruments, including the Claims-based Frailty Indicator, Clinical Frailty Scale, Hospital Frailty Risk score, and Critical Limb Ischemia Frailty Index. Data were extracted into a predefined workbook; risk of bias was appraised with the Quality In Prognosis Studies tool. Effect estimates were analyzed on the logarithmic scale. When pooling was possible, a random-effects model was fitted using restricted maximum likelihood in the metafor package in R. One prioritized contrast per study per outcome group was used to avoid double-counting. When fewer than two independent studies were available for an outcome group, results were summarized descriptively. Three studies were eligible for the main quantitative synthesis, and three additional studies were summarized in narrative or sensitivity analyses. Only one outcome group, the composite of death or major amputation, contained at least two independent studies and was pooled. The exploratory pooled hazard ratio for the prioritized highest/binary frailty contrast versus the lowest/non-frail reference group was 1.81 (95% confidence interval = 0.97-3.39; k = 2; τ² = 0.18; I² = 89.0%; Cochran Q-test p = 0.003 for heterogeneity). This estimate crossed the null. All remaining outcome groups (all-cause mortality, in-hospital mortality, major amputation, readmission mortality, unplanned readmission, and readmission due to major adverse cardiovascular events) were informed by a single study each and were described narratively. Publication bias was not formally assessed because no outcome group reached the prespecified threshold of 10 independent studies. Frailty was generally associated with worse outcomes in individual studies, but pooled evidence was limited to one exploratory outcome and did not reach statistical significance. Standardized, prospective, endovascular-specific studies are needed before firm conclusions can be drawn.