Managing antithrombotic therapy in older patients with both atrial fibrillation (AF) and stable coronary artery disease (CAD) presents a clinical challenge, balancing the risks of thrombotic events and bleeding. A new post hoc analysis of the AFIRE trial sought to clarify whether the effects of rivaroxaban monotherapy differ across age groups compared to combination therapy with an antiplatelet agent.¹˒²

This study was a post hoc secondary analysis of the Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease (AFIRE) trial, an open-label, randomised clinical trial conducted in Japan.¹ The analysis included 2,215 patients with AF and stable CAD, who had undergone percutaneous coronary intervention or coronary artery bypass grafting more than one year earlier, or had angiographically confirmed CAD not requiring revascularisation.

Participants were randomised to receive either rivaroxaban monotherapy or rivaroxaban plus an antiplatelet agent. For this analysis, they were stratified into four age groups: <70 years, 70–74 years, 75–79 years, and ≥80 years.

The primary efficacy endpoint was a composite of major adverse cardiovascular events (MACE), defined as stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularisation, or death from any cause. The primary safety endpoint was major bleeding.

For the primary efficacy endpoint, rivaroxaban monotherapy demonstrated a consistent benefit, particularly in the oldest patients. The hazard ratio (HR) for MACE with monotherapy versus combination therapy was 0.74 in patients <70 years, 1.16 in those aged 70–74, 0.72 in those aged 75–79, and 0.61 in those ≥80 years. The interaction by age was not statistically significant (p=0.51).

Regarding the primary safety endpoint, the benefit of monotherapy was most pronounced in the youngest age group. The HR for major bleeding was 0.23 for patients <70 years, 0.91 for those aged 70–74, 0.52 for those aged 75–79, and 0.67 for those ≥80 years. Again, the p-value for interaction did not reach statistical significance (p=0.33).

The AFIRE investigators concluded that the findings show “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.”¹

The authors suggest that the observed trends require further investigation. “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,” they stated.¹

References

1. Yamaguchi J, Arashi H, Hagiwara N, et al. Age-Stratified Effect of Rivaroxaban Monotherapy for Atrial Fibrillation in Stable Coronary Artery Disease: A Post Hoc Analysis of the AFIRE Randomized Clinical Trial. JAMA Cardiol. 2025. https://doi.org/10.1001/jamacardio.2025.2611.

2. Yasuda S, Kaikita K, Akao M, et al. Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease. N Engl J Med 2019; 381:1103-1113. https://doi.org/10.1056/NEJMoa1904143.

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