A groundbreaking study has revealed that edoxaban monotherapy is superior to dual therapy with edoxaban plus a single antiplatelet agent in reducing net adverse clinical events in patients with high-risk atrial fibrillation (AF) and stable coronary artery disease (CAD). The findings, presented at the European Society of Cardiology (ESC) Congress 2024 and simultaneously published in the New England Journal of Medicine, provide valuable insights into the optimal antithrombotic strategy for this patient population.
The EPIC-CAD trial, an investigator-initiated, open-label, randomized study, enrolled 1,040 patients from 18 major cardiac centers in South Korea. Eligible participants had high-risk AF, defined by a CHA2DS2-VASc score of 2 or higher, and stable CAD. Patients were randomly assigned to receive either standard-dose edoxaban monotherapy or dual therapy with standard-dose edoxaban plus a single antiplatelet agent (aspirin or clopidogrel).
The primary endpoint of the study was a net composite outcome, including death from any cause, stroke, systemic embolism, myocardial infarction, unplanned revascularization, and major or clinically relevant non-major bleeding at one year after randomization.
Over the 12-month follow-up period, edoxaban monotherapy significantly reduced the risk of the primary endpoint by 56% compared to dual therapy (6.8% vs. 16.2%; hazard ratio [HR] 0.44; 95% confidence interval [CI] 0.30−0.65; p<0.001). This difference was primarily driven by a 66% reduction in the risk of major bleeding or clinically relevant non-major bleeding with edoxaban monotherapy compared to dual therapy (4.7% vs. 14.2%; HR 0.34; 95% CI 0.22−0.53). Rates of major ischemic events were similar between the two groups (1.6% for monotherapy vs. 1.8% for dual therapy; HR 1.23; 95% CI 0.48−3.10), and there was no significant difference in all-cause mortality (0.6% for monotherapy vs. 0.7% for dual therapy; HR 1.29; 95% CI 0.29−5.76).
“Our results are similar with the AFIRE trial in patients with AF and stable CAD, which showed that rivaroxaban monotherapy was non-inferior to dual therapy for efficacy and superior for safety,” said Dr. Gi-Byoung Nam, the study presenter from the Asan Medical Center in Seoul, South Korea. “EPIC-CAD provides additional new evidence on the appropriate antithrombotic strategy with standard-dose edoxaban to guide the treatment of patients with AF and stable CAD.”
The findings of the EPIC-CAD trial align with current guidelines that recommend oral anticoagulant monotherapy for patients with AF and stable CAD. By demonstrating the superiority of edoxaban monotherapy over dual therapy in reducing net adverse clinical events, primarily driven by a lower risk of bleeding, the study reinforces the need for a more tailored approach to antithrombotic therapy in this patient population.
As the medical community continues to explore optimal treatment strategies for patients with AF and stable CAD, the EPIC-CAD trial provides valuable evidence to support the use of edoxaban monotherapy as a safe and effective long-term antithrombotic therapy.