Systematic Review and Network Meta-Analysis of the Efficacy and Safety of Antithrombotic Options following Open Surgical Revascularization for Peripheral Arterial Disease.

Background: We performed a systematic review and network meta-analysis to compare the efficacy and safety of different antithrombotic therapies following open surgical revascularization for peripheral arterial disease.

Methods: Ovid MEDLINE ®, EMBASE, and Cochrane CENTRAL databases were searched from inception until December 2023 for randomized controlled trials. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Primary efficacy outcomes were major adverse cardiovascular events (MACE) and major adverse limb events, and the primary safety outcome was major bleeding. Bayesian Network meta-analysis was used to facilitate comparison.

Results: Eighteen trials randomizing 9,453 patients were included. Most trials had at least "some concerns" on Risk of Bias assessment. Vitamin K antagonists likely result in a reduction in MACE when compared to low-dose aspirin (LDA) (relative risk [RR] 0.70, 95% confidence interval (CI) 0.51-0.94; the Grading of Recommendations Assessment, Development, and Evaluation [GRADE] certainty: moderate) with a probable large increase in major bleeding (RR 1.88, 95% CI 1.39-2.57; GRADE certainty: moderate). When rivaroxaban and LDA combination is compared to LDA monotherapy, there may be no difference in MACE (RR 0.82, 95% CI 0.58-1.16; GRADE certainty: low) or major adverse limb events (RR 0.91, 95% CI 0.77-1.07; GRADE certainty: moderate).

Conclusion: We have highlighted the superiority of vitamin K antagonists in reducing risk of MACE, albeit with an associated increased risk of bleeding. Our findings underscore the urgent need for further adequately powered trials to identify an optimal antithrombotic strategy following surgical revascularization. Future research must prioritize stratification by graft subtype and incorporates quantifiable bleeding risk to allow for a more tailored approach to antithrombotic therapy.