Background: In the AFIRE trial, rivaroxaban monotherapy was noninferior to combination therapy with rivaroxaban and an antiplatelet agent for thromboembolic events or death, and superior for major bleeding in patients with atrial fibrillation (AF) and stable coronary artery disease. Little is known about impacts of stroke and bleeding risks on the efficacy and safety of rivaroxaban monotherapy. Methods: In this subanalysis of the AFIRE trial, we assessed the risk of stroke and bleeding by the CHADS2, CHA2DS2-VASc, and HAS-BLED scores. The primary efficacy end point was the composite of stroke, systemic embolism, myocardial infarction (MI), unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding defined by the International Society on Thrombosis and Haemostasis. Results: Rivaroxaban monotherapy significantly reduced the primary efficacy and safety end points with no evidence of differential effects by stroke risk (CHADS2, p for interaction = 0.727 for efficacy, 0.395 for safety; CHA2DS2-VASc, p for interaction = 0.740 for efficacy, 0.265 for safety) or bleeding risk (HAS-BLED, p for interaction = 0.581 for efficacy, 0.225 for safety). There was also no evidence of statistical heterogeneity across patient risk categories for other end points; stroke or systemic embolism, ischemic stroke, hemorrhagic stroke, MI, MI or unstable angina, death from any cause, any bleeding, or net adverse clinical events. Conclusions: The advantages of rivaroxaban monotherapy compared with those of combination therapy with respect to all prespecified end points, including thromboembolism, bleeding, and mortality were similar across patients with AF and stable coronary artery disease, irrespective of their risk for stroke and bleeding. Clinical Trial Registration: UMIN Clinical Trials Registry number, UMIN000016612, and ClinicalTrials.gov number, NCT02642419.
All Science Journal Classification (ASJC) codes