For stable coronary artery disease plus atrial fibrillation, rivaroxaban alone is better than rivaroxaban plus aspirin

Reference

Yasuda S, Kaikita K, Akao M, et al, for the AFIRE Investigators. Antithrombotic therapy for atrial fibrillation with stable coronary disease. N Engl J Med 2019;381(12):1103-1113.

Synopsis

Many patients who receive dual antiplatelet therapy also have an indication for anticoagulation, such as atrial fibrillation. Current guidelines recommend a brief period of triple therapy with dual antiplatelet therapy plus an anticoagulant for the periprocedural period, followed by 1 to 12 months of an anticoagulant plus a P2Y12 inhibitor, followed by oral anticoagulant alone. This study compared monotherapy with the direct oral anticoagulant rivaroxaban with rivaroxaban plus an antiplatelet agent in 2215 adults with atrial fibrillation who had undergone PCI or bypass surgery at least 12 months previously, or had stenosis of at least 50% in one coronary vessel. All patients also had a score of at least 1 on the older CHADS2 scale, which puts them at moderate to high risk for stroke. The dosage of rivaroxaban was 15 mg once daily (10 mg once daily if creatinine clearance was 15 mL to 49 mL per minute) and 70% of the patients received aspirin as their antiplatelet agent. Groups were balanced at the start of the study with a mean age of 74 years, 79% were men, and 71% having undergone a PCI, most receiving a drug-eluting stent. Atrial fibrillation was paroxysmal in 53% of patients; persistent or permanent in 47%. This was a noninferiority trial with a primary endpoint that was a broad composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death; analysis was by modified intention to treat of all patients who underwent randomization. The trial was terminated after a median follow-up of 23 months because of an excess of deaths in the dual therapy group. The primary endpoint was significantly less likely in the rivaroxaban monotherapy group (4.14% vs 5.75% per year; P < .001; number needed to treat [NNT] = 61 per year). Regarding individual outcomes, death (1.85 vs 3.37%; P < .05; NNT = 66 per year), hemorrhagic stroke (0.18% vs 0.60%; P < .05; NNT = 312), and major bleeding (1.62% vs 2.76%; P = .01; NNT = 88 per year) were all less likely with rivaroxaban monotherapy. The benefit was consistent regardless of initial CHA2DS2-VASc score for stroke risk or HAS-BLED score for bleeding risk. Although the subgroup analyses should be considered exploratory, the benefit was greater for men than for women, for patients undergoing PCI rather than coronary artery bypass grafting, and for patients 75 years or older. This study was funded by the Japanese Research Foundation, but under a contract with Bayer Yakuhin.