Clinical question: Is there a difference in total thrombotic and/or bleeding events in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) on rivaroxaban monotherapy versus a combination of rivaroxaban and antiplatelet agent?
Background: The Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) trial showed that in patients with AF and CAD, rivaroxaban monotherapy had lower rates of first-time cardiovascular and bleeding events than rivaroxaban in combination with an antiplatelet agent. However, the initial evaluation of this trial did not account for subsequent thrombotic or bleeding events, raising concern for potential underestimation of the long-term risk associated with rivaroxaban monotherapy versus combination therapy.
Study design: Post-hoc secondary analysis of an open-label, randomized, clinical trial
Setting: Multicenter, Japan
Synopsis: In this study conducted across 294 centers, 2,215 patients were randomly assigned to rivaroxaban monotherapy, or therapy with rivaroxaban in combination with aspirin or a P2Y12 inhibitor. All patients were diagnosed with AF with a CHADS2 score greater than one, as well as confirmed CAD without percutaneous coronary intervention (PCI) or coronary artery bypass grafting within 12 months. Primary endpoints were the total number of first and subsequent bleeding and thrombotic events over a 24-month follow-up period. Thrombotic events included ischemic stroke, systemic embolism, myocardial infarction, and unstable angina requiring PCI. The total event rate was 12.2% and 19.2% for the monotherapy and combination therapy groups, respectively. Rivaroxaban monotherapy had a 31% reduction in first events and a 54% reduction in subsequent events. The rivaroxaban and combination-therapy groups had mortality rates of 3.7% and 6.6%, respectively. The mortality rate of bleeding events was higher than that of thrombotic events, regardless of the treatment group. Limitations include open-label study design and minimal patient diversity. The 24-month follow-up period may not fully capture the lifetime risk of events.
Bottom line: Rivaroxaban monotherapy as compared to rivaroxaban in combination with an antiplatelet agent for patients with AF and stable CAD is associated with a reduction in both first-time and total number of thrombotic and bleeding events.
Citation: Naito R, et al. AFIRE Investigators. Rivaroxaban monotherapy vs combination therapy with antiplatelets on total thrombotic and bleeding events in atrial fibrillation with stable coronary artery disease: A post hoc secondary analysis of the AFIRE trial. JAMA Cardiol. 2022;7(8):787-94.
Dr. Clemo is an assistant professor of medicine at the University of Virginia School of Medicine, Charlottesville, Va.