Dual antiplatlets therapy following revasclarisation for chronic critical limb ischemia: A systematic review and meta-analysis

Introduction: Chronic limb-threatening ischaemia carries high risks of amputation and death despite revascularisation. Clinicians frequently prescribe dual antiplatelet therapy after surgical or endovascular procedures, yet its net clinical benefit remains uncertain. This review aimed to compare the effectiveness and safety of dual antiplatelet therapy versus single antiplatelet therapy following lower-limb revascularisation. Methods: The study followed PRISMA 2020 and Cochrane guidance, registered a protocol, and included randomized trials of adults with chronic limb-threatening or critical limb ischaemia after lower-limb revascularisation. Dual therapy combined aspirin with a P2Y12 inhibitor versus single agent. Searches covered databases to 20 September 2025. Triplicate screening, extraction, Risk-of-Bias 2, random-effects Paule–Mandel with Hartung–Knapp, rare-event methods, subgroups, and GRADE were prespecified. Results: The search retrieved 6,416 citations after de-duplication; 10 randomized trials met eligibility for synthesis. For major amputation at one year, the random-effects risk ratio was 0.94 (95% CI 0.77–1.15; I² 89.9%). Twelve-month graft patency showed no improvement (RR 1.16, 95% CI 0.70–1.91; I² 95.5%). Major bleeding or transfusion increased with dual therapy (RR 1.55, 95% CI 1.06–2.26; I² 57.4%). Resting ankle–brachial index showed minimal difference (MD −0.04, 95% CI −0.11 to 0.02; I² 99.5%). All-cause mortality at one year was neutral (RR 1.01, 95% CI 0.75–1.35; I² 91.7%). Subgroup analyses found no interaction by vascular bed, modality, or duration; small-study effects were generally suggested; overall certainty was moderate for amputation and patency, and low for bleeding and mortality across trials. Conclusion: Dual antiplatelet therapy after lower-limb revascularisation for chronic limb-threatening ischaemia did not reduce major amputation or improve patency under random-effects assumptions, and it increased major bleeding. Mortality appeared neutral. Effects varied widely across studies without subgroup effects. Treatment decisions should individualize bleeding risk and limb threat while awaiting powered trials.