Rivaroxaban Mono vs. Combo Therapy for Thrombotic and Bleeding Events in AF

Quick Takes

  • Rivaroxaban monotherapy is associated with fewer thrombotic and/or bleeding events than combination rivaroxaban-antiplatelet therapy.
  • Mortality risk is lower after a thrombotic event than a major bleeding event.
  • Patients with AF and stable CAD should be considered for direct oral anticoagulant monotherapy without the use of antiplatelet medications.

Study Questions:

How did the total number of thrombotic and/or bleeding events differ between patients randomized to receive rivaroxaban monotherapy or combination rivaroxaban plus antiplatelet therapy?


The AFIRE trial was an open-label, randomized trial of patients with atrial fibrillation (AF) and stable coronary artery disease (CAD) who had undergone percutaneous coronary intervention or coronary artery bypass grafting ≥12 months prior. Patients were enrolled between September 2020–March 2021 and randomized to receive either rivaroxaban monotherapy (without antiplatelet therapy) or rivaroxaban plus antiplatelet therapy. The primary outcome of this post hoc secondary analysis is the total incidence of thrombotic, bleeding, and fatal events in the two groups. Cox regression analysis was used to estimate the risk of events in the two groups.


Among a total of 2,215 patients (mean age 74 years, 79% men) in the modified intention-to-treat analysis, the total event rate was 12.2% for the rivaroxaban monotherapy group and 19.2% (50.0%) for the rivaroxaban plus antiplatelet therapy group over a median follow-up of 24.1 months (hazard ratio, 0.62; 95% confidence interval, 0.48-0.80). Mortality was lower in the monotherapy group as compared to the combination therapy group (3.7% vs. 6.6%). Mortality risk after a bleeding event (75% in monotherapy and 62.1% in combination therapy groups) was higher as compared to after a thrombotic event (25% in monotherapy and 37.9% in combination therapy).


The authors concluded that rivaroxaban monotherapy was associated with a lower risk of total thrombotic and/or bleeding events than combination therapy for patients with AF and stable CAD.


The past several years have focused on a “less-is-more” approach for patients with concomitant AF and CAD. While several trials have compared different medication regimens in patients with AF and acute coronary syndrome or undergoing percutaneous coronary intervention, the AFIRE trial is one of the few to study patients with stable CAD (≥12 months since any coronary intervention). The post hoc analysis confirms that the total thrombotic and/or bleeding events were fewer among the patients randomized to rivaroxaban monotherapy as compared to rivaroxaban plus antiplatelet combination therapy. Furthermore, it demonstrates that mortality is higher after a major bleeding event than after a thromboembolic event, no matter if antiplatelet therapy is given or not. This provides further support for the less-is-more concept, including the use of direct oral anticoagulant monotherapy in patients with AF and stable CAD.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, Arrhythmias and Clinical EP, Cardiac Surgery, Geriatric Cardiology, Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), Anticoagulation Management and ACS, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Aortic Surgery, Cardiac Surgery and Arrhythmias, Interventions and ACS, Interventions and Coronary Artery Disease

Keywords: Acute Coronary Syndrome, Anticoagulants, Arrhythmias, Cardiac, Atrial Fibrillation, Coronary Artery Bypass, Coronary Artery Disease, Geriatrics, Hemorrhage, Myocardial Ischemia, Percutaneous Coronary Intervention, Platelet Aggregation Inhibitors, Secondary Prevention, Thrombosis, Vascular Diseases

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