Key result
Rivaroxaban plus aspirin reduces MACE ~18% vs. aspirin alone in peripheral artery disease.
Why the study?
Although aspirin is the cornerstone of therapy in peripheral artery disease, residual thrombotic risk persists, and the addition of rivaroxaban may enhance protection through dual pathway inhibition.
Does rivaroxaban plus aspirin reduce major adverse cardiovascular events compared to aspirin alone in patients with peripheral artery disease?
Meta-Analysis (n=90,325)
Yes
Does rivaroxaban plus aspirin reduce major adverse cardiovascular events compared to aspirin alone in patients with peripheral artery disease?
Relative Risk: 0.82 (95% CI 0.78–0.87)
Dual pathway inhibition with rivaroxaban and aspirin provides significant cardiovascular and limb protection in patients with peripheral artery disease, but requires careful patient selection due to an increased risk of major bleeding.
Supports rivaroxaban plus aspirin for MACE reduction in PAD with bleeding caution; confirms and extends prior RCTs in pooled analysis of 90,325 patients.
Background: Peripheral artery disease (PAD) is a prevalent atherosclerotic disorder associated with significant cardiovascular morbidity. Although aspirin remains the cornerstone of therapy, residual thrombotic risk persists. The addition of rivaroxaban, a factor Xa inhibitor, may enhance protection through dual pathway inhibition. This meta-analysis aimed to evaluate the efficacy and safety of rivaroxaban plus aspirin versus aspirin alone in patients with PAD. Methods: A systematic review and meta-analysis were conducted following PRISMA and AMSTAR guidelines. Randomized controlled trials comparing rivaroxaban plus aspirin with aspirin alone in adults with PAD were included. Data were pooled using a random-effects model in Review Manager 5.4. Risk of bias was assessed with RoB 2 and certainty of evidence was graded using GRADE pro. Results: Six RCTs including 90 325 participants met inclusion criteria. Combination therapy significantly reduced MACE (RR: 0.82, 95% CI: 0.78–0.87), MI (RR: 0.87), ischemic stroke (RR: 0.76), and acute limb ischemia (RR: 0.68), with low heterogeneity (≤35%). No significant reduction was observed in cardiovascular mortality or major amputation. TIMI major bleeding risk increased (RR: 1.41, 95% CI: 1.07–1.84), however intracranial and fatal bleeding rates were similar between groups. Moderate-to-high certainty evidence supports reductions in ischemic and limb events, with increased bleeding risk. Conclusion: Rivaroxaban plus aspirin is associated with improved cardiovascular and limb outcomes compared to aspirin alone in PAD, albeit with a higher risk of major bleeding. Findings should be interpreted in the context of potential publication bias and heterogeneity across trials. Careful patient selection is warranted for optimal risk-benefit balance.
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Farhan et al. (2026) conducted a meta-analysis in Peripheral artery disease (PAD) (n=90,325). Rivaroxaban plus aspirin vs. Aspirin alone (or placebo plus aspirin) was evaluated on MACE (composite of myocardial infarction, ischemic stroke, and cardiovascular death) (RR 0.82, 95% CI 0.78-0.87). Rivaroxaban plus aspirin significantly reduced major adverse cardiovascular events (RR 0.82) compared to aspirin alone in patients with peripheral artery disease.
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