In patients with high-risk atrial fibrillation (AFib) and stable coronary artery disease, endoxaban monotherapy when given as a long-term antithrombotic therapy was associated with better net clinical benefit than edoxaban plus a single antiplatelet agent, based on findings from the EPIC-CAD trial presented at ESC Congress 2024 in London and simultaneously published in The New England Journal of Medicine (NEJM).

The trial randomized 1,040 patients from 18 sites in South Korea to either edoxaban monotherapy (n=524) or dual antithrombotic therapy (n=516). Across all participants, the mean age was 72.1 years, 22.9% were women, and the mean CHA2DS2-VASc score was 4.3. The primary outcome was a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major bleeding or clinically relevant nonmajor bleeding at 12 months.

At 12 months, a primary-outcome event had occurred in 34 patients (6.8%) receiving edoxaban monotherapy and in 79 patients (16.2%) receiving dual antithrombotic therapy. Researchers noted that the cumulative incidence of major ischemic events during this period appeared to be similar both groups. Additionally, major bleeding or clinically relevant nonmajor bleeding was lower in the edoxaban monotherapy group, occurring in 23 patients vs. 70 patients in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI, 0.22 to 0.53).

"There was a lack of evidence regarding the best maintenance antithrombotic strategy in patients with high-risk AFib and stable [coronary artery disease], particularly as long-term dual therapy with an oral anticoagulant and an antiplatelet drug may increase the risk of bleeding," said Gi-Byoung Nam, MD, who presented the study. "In the EPIC-CAD trial, we were able to show that edoxaban monotherapy resulted in fewer net adverse clinical events compared with dual antithrombotic therapy in the 12 months after randomization, with less clinically important bleeding and no increase in major ischemic events."

In a related editorial comment published in NEJM, Gregory Y.H. Lip, MD, FACC, writes that the trial "provides additional reassurance for prescribing oral anticoagulant monotherapy for patients with AFib and stable vascular disease," but adds that "further studies involving non-Asian cohorts may be needed."