Efficacy of colchicine in lower extremity peripheral arterial disease: A meta-analysis

Background: Lower-extremity peripheral arterial disease (LEPAD) significantly increases the risk of severe cardiovascular and limb complications, often due to the underlying inflammation from atherosclerosis. Colchicine has gained attention due to its efficacy in the primary and secondary prevention of cardiovascular events and may offer similar protective benefits for LEPAD. Objectives: This meta-analysis aimed to evaluate outcomes with colchicine in LEPAD. Methods: A systematic literature search was performed on the major bibliographic databases for studies until October 2024. Hazard ratios (HRs) with their corresponding 95% CIs were pooled using the inverse-variance random-effects model. Results: Three studies were included with 226,804 patients [113,537: Colchicine and 113,267: Placebo]. The pooled analysis demonstrates colchicine use in patients with LEPAD was associated with a significantly lower risk of major adverse limb events (MALE) [HR: 0.84; 95 % CI: 0.75, 0.94; p = 0.002], major adverse cardiovascular events (MACE) [HR: 0.90; 95 % CI: 0.82, 0.98; p = 0.02], ischemic stroke [HR: 0.97; 95 % CI: 0.94, 0.99; p = 0.02], need for major amputations [HR: 0.81, 95 % CI: 0.75, 0.87; p< 0.00001], and revascularization for lower limb ischemia [HR: 0.81; 95 % CI: 0.72, 0.90; p = 0.0001]. However, no significant reduction was noted for allcause mortality [HR: 0.87; 95 % CI: 0.74, 1.02; p = 0.09] and myocardial infarction (MI) [HR: 0.98; 95 % CI: 0.95, 1.00; p = .10]. Conclusion: Colchicine may be a useful adjunctive therapy for reducing the risk of major cardiovascular and limbrelated complications in patients with LEPAD, including lower rates of MACE, MALE, stroke, amputation, and limb ischemia. However, it did not significantly reduce all-cause mortality or MI. Notably, the only randomized trial evaluating colchicine's efficacy in LEPAD reported a similar risk of adverse outcomes. Multicenter, adequately powered randomized controlled trials are needed to confirm colchicine's effectiveness in this population.