Rivaroxaban Monotherapy Noninferior to Combination Therapy for AFib

A recent study comparing rivaroxaban monotherapy to combination therapy in patients with atrial fibrillation with stable coronary artery disease found monotherapy was non inferior for efficacy and superior for safety.

Results of the Atrial Fibrillation and Ischemic Events with Rivaroxaban in Patients with Stable Coronary Artery Disease (AFIRE) study, which included more than 2000 patients, were presented at the European Society of Cardiology’s ESC Congress 2019.

In an effort to further data on the use of antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease, investigators carried out a multicenter, open-label, randomized trial in a cohort of 2236 patients with atrial fibrillation. All patients included in the study had undergone percutaneous intervention (PCI) or coronary-artery bypass grafting (CABG) more than 1 year earlier or had geographically confirmed coronary artery disease no requiring revascularization.

All patients involved in the study were from Japan and at least 20 years old or older. Additional exclusion criteria included a history of stent thrombosis, coexisting active tumor, and poorly controlled hypertension.

Patients included in the study were randomized in a 1:1 ratio to receive rivaroxaban — 10 mg for patients with a creatinine clearance off 15 to 49 ml per minute or 15 mg for patients with a creatinine clearance of 50 or more ml per minute — or combination therapy with rivaroxaban plus either aspirin or a P2Y12 inhibitor. Follow-up assessments were planned at baseline, at 6 months, and at the end of the trial. The follow-up period was planned to be at least 24 and up to 45 months.

Primary efficacy measure for the study was a composite of stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or death from any cause. The primary safety end point of the study was major bleeding. Secondary end points for the trial included death from any cause, a composite of ischemic cardiovascular events or death, adverse clinical events, and any bleeding events.

The mean age of the 2215 patients who were included in the intention-to-treat population was 74 years and 79% of the population group was male. Of the 2215, 70.6% had undergone previous PCI and 11.4% had undergone previous CABG. In the combination therapy group, 70.2% of patients received aspirin and 26.8% received a P2Y12 inhibitor.

Investigators noted that the evaluation of patients was terminated 3 months prior to planned completion as an independent data safety and monitoring committee recommended early termination due to a higher risk of death from any cause in the combination therapy group. Median treatment duration for the trial was 23 months and the median follow-up duration was 24.1 months.

Upon analyses, rivaroxaban monotherapy was noninferior to combination therapy for the primary efficacy end point with event rates of 4.14% per patient-year with monotherapy and 5.75% with combination therapy (HR, 0.72; 95% CI, 0.55 to 0.95; P<0.001 for noninferiority). In regard to the safety endpoint, monotherapy was superior to combination therapy with event rates of 1.62% and 2.76% per patient-year, respectively (HR, 0.59; 95% CI, 0.39 to 0.89; P=0.01 for superiority).

This study, “Antithrombotic Therapy for Atrial Fibrillation with Stable Coronary Disease,” was presented at ESC Congress 2019 in Paris.