Antithrombotic Strategies After Lower-Extremity Revascularization in Chronic Limb- Threatening Ischemia: A Systematic Review and Network Meta-Analysis

<h2>Abstract</h2><h3>Objective</h3> To compare single antiplatelet therapy (SAPT), dual antiplatelet therapy (DAPT), and dual-pathway inhibition (DPI; rivaroxaban plus aspirin) for the prevention of major adverse limb events (MALE) after lower-extremity revascularization in chronic limb-threatening ischemia (CLTI). <h3>Methods</h3> We performed a systematic review and frequentist network meta-analysis following PRISMA 2020 and PRISMA-NMA guidelines and a prespecified PROSPERO protocol. MEDLINE, Embase, Scopus, CENTRAL, ClinicalTrials.gov, and WHO ICTRP were searched through December 2025. Comparative randomized and observational studies reporting hazard ratios (HRs) for time-to-event outcomes after endovascular or surgical revascularization were eligible. Outcomes included MALE, acute limb ischemia (ALI), major adverse cardiovascular events (MACE), major bleeding, and all-cause mortality. Risk of bias was assessed using RoB-2 and ROBINS-I. <h3>Results</h3> Five studies contributed to the MALE network. <b>DAPT and SAPT demonstrated similar MALE risk</b> (HR 1.10; 95% CI 0.81–1.27). Compared with SAPT, <b>DPI was associated with a lower risk of MALE</b> (HR 0.74; 95% CI 0.64–0.86). However, when indirectly compared with DAPT, <b>DPI showed a significantly higher MALE risk</b> (HR 1.48; 95% CI 1.10–2.01). Three studies contributed to the ALI network, where <b>DPI was associated with increased ALI risk compared with SAPT</b> (HR 1.46; 95% CI 1.25–1.70). No strategy demonstrated significant superiority for MACE, major bleeding, or all-cause mortality, although estimates were imprecise for DAPT. Heterogeneity and inconsistency were low across networks, and sensitivity analyses yielded similar results. <h3>Conclusions</h3> In CLTI populations undergoing lower-extremity revascularization, <b>SAPT and DAPT exhibit comparable limb protection</b>, while <b>DPI demonstrates a mixed profile: reduced MALE versus SAPT but worse outcomes compared with DAPT and a higher risk of ALI</b>. No clear cardiovascular or bleeding advantage was identified for any strategy. These findings suggest that antithrombotic selection in CLTI should be individualized, and the role of DPI remains uncertain pending dedicated limb-focused trials.