Study Summary

The AFIRE trial assessed the management of patients with AF, stable CAD, and either a history of PCI or CABG at least 1 year before enrollment, or stenosis ≥50% not requiring revascularization. Patients were randomly assigned to receive rivaroxaban (15 mg daily for CrCl ≥50 mg/min, or 10 mg daily for CrCl 15–50 mg/min; n = 1,118) or rivaroxaban plus an antiplatelet agent (either aspirin or a P2Y12 inhibitor; n = 1,118). During follow-up (mean 24 months), the incidence of the primary efficacy outcome (all-cause mortality, MI, stroke, unstable angina, or systemic embolism) was 4.14% per patient-year in the monotherapy group and 5.75% per patient-year in the combination therapy group (HR 0.72; P < 0.001 for noninferiority). The incidence of the primary safety endpoint (ISTH criteria major bleeding) was 1.62% per patient-year in the monotherapy group and 2.76% per patient-year in the combination therapy group (HR 0.59, P = 0.01).

Commentary

Study Strengths: The AFIRE trial was a large, multicenter, randomized clinical study, which had sufficient statistical power to show noninferiority of rivaroxaban monotherapy for the primary efficacy outcome and superiority for the primary safety outcome. The trial was terminated early after an increased rate of all-cause death was reported in the combination therapy group.

Study Limitations: The study was performed in Japan and used the dose of rivaroxaban approved in Japan, which is lowerthan that used used throughout most of the rest of the world. In the combination therapy group, the trust had an open label design such that the choice between aspirin or P2Y12 inhibitor was made by the investigator.

Next Steps/Clinical Perspective: The AFIRE trial builds on the results of previous trials and provides strong evidence to support the clinical use of oral anticoagulation alone without antiplatelet therapy in patients with AF and stable CAD who are at least 1 year on from revascularization.

Trial Reference

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Yasuda  S, Kaikita  K, Akao  M, et al. Antithrombotic therapy for Atrial Fibrillation with Stable Coronary Disease. N. Engl. J. Med. doi: 10.1056/NEJMoa1904143.