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Funding Acknowledgements Type of funding sources: None. Background Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis which strongly correlates to cardiovascular morbidity and mortality and increased risk of limb loss, and despite the wide use of guideline-based antiplatelet therapy, patients remain at high risk for cardiovascular and limb events. There has been increasing interest in novel anticoagulants to improve prevention of complications secondary to PAD. Purpose This study aims to determine the effectiveness and safety of combined direct oral anticoagulant plus antiplatelet in reducing MACE, MALE and all-cause mortality among patients with PAD. Method Randomized controlled trials with outcomes on major adverse cardiac events (MACE), major adverse limb events (MALE), all-cause mortality and bleeding were searched through PubMed, Cochrane and EBSCOHost. Result Pooled analysis of studies on patients peripheral arterial disease showed that anticoagulant combined with antiplatelet have significant benefits compared with antiplatelet alone in reducing major adverse limb events (RR 0.72, 95% CI 0.62 to 0.83) and stroke (RR 0.74, 95% CI 0.57 to 0.97) but had inconclusive results in reducing myocardial infarction (RR 0.85, 95% CI 0.70 to 1.03).There was no significant benefit in reducing cardiovascular death (RR 1.04, 95% CI 0.88 to 1.23) and all-cause mortality (RR 1.02, 95% CI 0.90 to 1.16). Likewise, there was increased risk of bleeding (RR 1.46, 95% CI of 1.18 to 1.80) compared with antiplatelet alone. Conclusion Anticoagulant (Rivaroxaban) combined with antiplatelet (aspirin) as alternative to traditional antiplatelet (aspirin) therapy significantly reduced major adverse limb events and stroke. However, there was a higher incidence of bleeding for the combined cohort. Therefore, it is deemed necessary to identify high-risk PAD patients with low risk of bleeding who can benefit the most with the combined intervention.

Effectiveness and safety of combined direct oral anticoagulant and antiplatelet among high-risk peripheral arterial disease: a meta-analysis