Rivaroxaban Monotherapy Linked to Lower Event Risk in Patients with AF, Stable CAD

New findings suggest rivaroxaban monotherapy was associated with low risk of total thrombotic and/or bleeding events in patients with atrial fibrillation and stable coronary artery disease (CAD).

Monotherapy was linked to lower risk of total events, including both the first and subsequent events, when compared to combination rivaroxaban and antiplatelet therapy.

“As societies continue to age around the world, bleeding may be a prominent issue on which to focus,” wrote corresponding author Katsumi Miauchi, MD, PhD, Department of Cardiovascular Medicine, Juntendo Tokyo Geriatric Medical Center. “Thus, clinicians will have to consider tapering antithrombotic agents in patients with AF after PCI to minimize their bleeding events.”

The secondary analysis of the Atrial Fibrillation and Ischemic Events with Rivaroxanab in Patients with Stable Coronary Artery Disease (AFIRE) study in Japan aimed to determine whether anticoagulant therapy alone compared with combination anticoagulant and antiplatelet therapy was associated with a lower incidence of total cardiovascular and/or bleeding events. It was conducted from February 2015 - July 2018.

The study enrolled patients (≥20 years) with AF and stable CAD who had undergone percutaneous coronary intervention (PCI) or coronary artery bypass grafting 1 or more years earlier or who had angiographically confirmed CAD not requiring revascularization.

Patients were equally randomized to either receive monotherapy with rivaroxaban (10 mg once daily for patients with a creatinine clearance of 15 to 49 mL/min or 15 mg once daily for patients with a creatinine clearance ≥50 mL/min) or combination therapy with rivaroxaban and an antiplatelet agent.

Investigators considered the primary endpoint to be the total number of first and subsequent events, including death, bleeding, and thrombotic events. They used Cox regression analyses to estimate the risk of subsequent events in each group, with the status of thrombotic or bleeding events that had occurred by the time of death used as a time-dependent variable.

From February 2015 to September 2017, a total of 2215 patients (mean age, 74 years; 1751 men [79.1%]) were included in the modified intention-to-treat analysis, according to investigators.

Data show the total event rates for the rivaroxaban monotherapy group (1107 [50.0%]) and the combination-therapy group (1108 [50.0%]) were 12.2% (135 of 1107) and 19.2% (213 of 1108) respectively, during a median follow-up of 24.1 months. They observed the mortality rate was 3.7% (41 of 1107) in the monotherapy group and 6.6% (73 of 1108) in the combination-therapy group.

Moreover, rivaroxaban monotherapy was associated with 38% lower cumulative hazard of total events, including death from any cause, hemorrhagic and ischemic stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, and major bleeding, than combination therapy (hazard ratio [HR], 0.62; 95% CI, 0.48 - 0.80; P <.001).

Of the patients who had first thrombotic or bleeding events and subsequently died, bleeding events accounted for 75% (6 of 8) in the monotherapy group and 62.1% (18 of 29) in the combination-therapy group. Investigators noted that bleeding events are clinically more impactful than thrombotic events in patients with AF and stable CAD receiving antithrombotic agents.

“This study extends the main findings of the AFIRE study, showing a reduction in not only the first events but in the total events,” Miauchi concluded. “These results reinforce the treatment benefit of rivaroxaban alone with respect to thrombosis and bleeding reduction.”

The study, “Rivaroxaban Monotherapy vs Combination Therapy with Antiplatelets on Total Thrombotic and Bleeding Events in Atrial Fibrillation with Stable Coronary Artery Disease: A Post Hoc Secondary Analysis of the AFIRE Trial,” was published in JAMA Cardiology.