Age-Stratified Effect of Rivaroxaban Monotherapy for Atrial Fibrillation in Stable Coronary Artery Disease: A Post Hoc Analysis of the AFIRE Randomized Clinical Trial

Abstract

Importance: Antithrombotic therapy is crucial for older patients with coronary artery disease (CAD) and atrial fibrillation (AF) who are at a high risk of bleeding and thrombotic events.

Objective: To examine the age-stratified effects of rivaroxaban monotherapy compared with those of rivaroxaban plus antiplatelet agent combination therapy.

Design, setting, and participants: This was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) open-label randomized clinical trial. This was a multicenter study conducted in Japan from February 23, 2015, to July 31, 2018. Patients with AF and stable CAD who had undergone percutaneous coronary intervention or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD that did not require revascularization were enrolled. Participants were stratified into 4 groups by age (<70 years, 70-74 years, 75-79 years, and ≥80 years). Study data were analyzed from August 2024 to July 2025.

Interventions: Rivaroxaban monotherapy or rivaroxaban plus antiplatelet agent therapy.

Main outcomes and measures: The primary efficacy end point was a major adverse cardiovascular event, defined as a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The primary safety end point was major bleeding.

Results: This study included a total of 2215 participants (mean [SD] age, 74.3 [8.2] years; 1751 male [79.1%]). The incidence of primary efficacy end points per patient-year for rivaroxaban monotherapy vs rivaroxaban plus antiplatelet agent therapy was 3.2% vs 4.3% (<70 years), 3.2% vs 2.8% (70-74 years), 3.8% vs 5.3% (75-79 years), and 6.2% vs 10.3% (≥80 years). The hazard ratios were 0.74 (95% CI, 0.40-1.37) for those younger than 70 years, 1.16 (95% CI, 0.55-2.45) for those aged 70 to 74 years, 0.72 (95% CI, 0.41-1.26) for those aged 75 to 79 years, and 0.61 (95% CI, 0.40-0.93) for those 80 years and older (P for interaction =.51). For the primary safety end points, the incidence was 0.5% vs 2.3% (<70 years), 2.2% vs 2.4% (70-74 years), 1.1% vs 2.1% (75-79 years), and 2.9% vs 4.3% (≥80 years). The hazard ratios were 0.23 (95% CI, 0.06-0.79) for those younger than 70 years, 0.91 (95% CI, 0.39-2.15) for those aged 70 to 74 years, 0.52 (95% CI, 0.19-1.42) for those aged 75 to 79 years, and 0.67 (95% CI, 0.35-1.27) for those 80 years and older (P for interaction =.33).

Conclusions and relevance: Results of this post hoc analysis of the AFIRE randomized clinical trial reveal that rivaroxaban monotherapy reduced the risk of major cardiovascular events and major bleeding across the broad range of age in patients with AF and stable CAD. Possible age-related differences in trends, with more pronounced efficacy in older patients and more pronounced safety in younger patients, should be considered as hypothesis generating and require further research.

Trial registration: ClinicalTrials.gov Identifier: NCT02642419.