Antithrombotic strategies after lower extremity revascularization in chronic limb-threatening ischemia: A systematic review and network meta-analysis
Year: 2026
Type: review
Study designs: Systematic Review, Meta-Analysis
Abstract: Objective 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 (MALEs) after lower extremity revascularization in chronic limb-threatening ischemia (CLTI). Methods We performed a systematic review and frequentist network meta-analysis following the PRISMA 2020 and PRISMA-NMA guidelines and a prespecified PROSPERO protocol. MEDLINE, Embase, Scopus, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trial Registry Platform 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, major bleeding, and all-cause mortality. Risk of bias was assessed using the RoB-2 and ROBINS-I tools. Results Five studies contributed to the MALE network. DAPT and SAPT demonstrated similar MALE risk (HR, 1.10; 95% confidence interval [CI], 0.81-1.27). Compared with SAPT, DPI was associated with a lower risk of MALE (HR, 0.74; 95% CI, 0.64-0.86). However, when indirectly compared with DAPT, DPI showed a significantly higher MALE risk (HR, 1.48; 95% CI, 1.10-2.01). Three studies contributed to the ALI network, where DPI was associated with increased ALI risk compared with SAPT (HR, 1.46; 95% CI, 1.25-1.70). No strategy demonstrated significant superiority for major adverse cardiovascular events, 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. Conclusions In CLTI populations undergoing lower extremity revascularization, SAPT and DAPT exhibit comparable limb protection, and DPI demonstrates a mixed profile: reduced MALE vs SAPT but worse outcomes compared with DAPT and a higher risk of ALI. 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. Clinical Relevance This network meta-analysis provides a comparative assessment of antithrombotic strategies after lower extremity revascularization in chronic limb-threatening ischemia (CLTI). Single antiplatelet therapy (SAPT) and dual antiplatelet therapy (DAPT) demonstrated similar major adverse limb event protection, with DAPT ranking as the most effective regimen overall. Dual-pathway inhibition showed a mixed profile: it reduced major adverse limb events compared with SAPT, but resulted in worse outcomes compared with DAPT and increased the risk of acute limb ischemia. No strategy demonstrated superiority for cardiovascular events, major bleeding, or mortality. These findings highlight the importance of individualized antithrombotic selection in CLTI, balancing limb-specific risk, ischemic burden, and bleeding susceptibility. Dedicated CLTI-focused randomized trials are needed to guide optimal postoperative therapy.
Source: JVS-Vascular Insights
Institution: Universidad de Guadalajara
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,000
OpenAlex ID: W7128792373