Rivaroxaban Monotherapy Effective Across Age Groups in Atrial Fibrillation Patients With Stable CAD: AFIRE Trial
Japan: A post hoc analysis of the AFIRE randomized clinical trial has demonstrated that rivaroxaban monotherapy offers a consistent net clinical benefit across different age groups in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). The study, published in JAMA Cardiology by Dr. Junichi Yamaguchi and colleagues from the Department of Cardiology, Tokyo Women’s Medical University, Japan, provides important insights into age-stratified outcomes of antithrombotic therapy.
Antithrombotic management in patients with AF and CAD is challenging, particularly among older adults who face increased risks of both bleeding and thrombotic complications. While previous studies have shown that rivaroxaban monotherapy is noninferior to combination therapy with rivaroxaban and an antiplatelet agent, questions remained about whether age modifies these outcomes.
To address this, the researchers analyzed data from 2,215 patients (mean age, 74.3 years; 79% male) enrolled in the AFIRE trial, which was conducted across multiple centers in Japan between 2015 and 2018. Participants had AF and stable CAD, defined as a history of percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) more than a year earlier, or angiographically confirmed CAD not requiring revascularization. Patients were randomized to receive either rivaroxaban monotherapy or rivaroxaban plus an antiplatelet agent and 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 stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The primary safety endpoint was major bleeding.
Key Results
- For patients under 70 years, event rates for rivaroxaban monotherapy vs combination therapy were 3.2% vs 4.3% per patient-year, with a hazard ratio (HR) of 0.74.
- In the 70–74 year group, the rates were 3.2% vs 2.8%, HR 1.16.
- For those aged 75–79 years, the rates were 3.8% vs 5.3%, HR 0.72.
- In patients aged 80 years and older, event rates were 6.2% vs 10.3%, HR 0.61.
- For major bleeding, rivaroxaban monotherapy consistently showed lower or comparable rates across all age categories, with the greatest safety advantage in patients under 70 years (0.5% vs 2.3%; HR 0.23).
Overall, rivaroxaban monotherapy demonstrated reduced risks of both major cardiovascular events and major bleeding across age groups. While older patients derived stronger efficacy benefits, younger patients appeared to experience greater safety advantages. Importantly, the study found no significant age-by-treatment interaction, indicating that the benefits of monotherapy were consistent irrespective of age.
The authors note that while these findings suggest age-related trends, they should be considered hypothesis-generating and warrant further investigation in future studies.
"The analysis supports rivaroxaban monotherapy as an effective and safe strategy for managing patients with atrial fibrillation and stable coronary artery disease across a wide age spectrum. These results reinforce the potential of simplified antithrombotic therapy in reducing complications without compromising efficacy," the authors concluded.
Reference:
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. Published online August 13, 2025. doi:10.1001/jamacardio.2025.2611
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