Rivaroxaban Monotherapy versus Combination Therapy According to Patient Risk of Stroke and Bleeding in Atrial Fibrillation and Stable Coronary Disease: AFIRE trial sub-analysis.

Abstract Background In the AFIRE trial, rivaroxaban monotherapy was non-inferior 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 (CAD). Little is known about impacts of stroke and bleeding risks on the efficacy and safety of rivaroxaban monotherapy. Methods In this sub-analysis of the AFIRE trial, we assessed the risk of stroke and bleeding by the CHADS2, CHA2DS2-VASc, and HAS-BLED scores. The primary efficacy endpoint was the composite of stroke, systemic embolism, myocardial infarction (MI), unstable angina requiring revascularization, or death from any cause. The primary safety endpoint was major bleeding defined by the International Society on Thrombosis and Haemostasis. Results Rivaroxaban monotherapy significantly reduced the primary efficacy and safety endpoints 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 endpoints; 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 pre-specified endpoints, including thromboembolism, bleeding, and mortality were similar across patients with AF and stable CAD, irrespective of their risk for stroke and bleeding. Clinical Trial Registration UMIN Clinical Trials Registry number, UMIN000016612, and ClinicalTrials.gov number, NCT02642419.