EPIC-CAD Supports Oral Anticoagulant Monotherapy in Patients with Atrial Fibrillation and Stable Coronary Disease

The EPIC-CAD trial, presented at ESC 2024 and published in The New England Journal of Medicine, addresses a crucial question in managing patients with both atrial fibrillation (AF) and stable coronary artery disease (CAD): Is combination antithrombotic therapy necessary, or can oral anticoagulant monotherapy be sufficient? Current European Society of Cardiology (ESC) guidelines recommend dual antithrombotic therapy, with oral anticoagulants and antiplatelets, during the initial months after percutaneous coronary intervention (PCI) or an acute coronary syndrome (ACS). However, in stable CAD patients with AF, uncertainty remains regarding the long-term optimal strategy for reducing thrombotic risk without increasing bleeding events.

Previous studies like the AFIRE and OAC-ALONE trials showed potential benefits of monotherapy with rivaroxaban or warfarin in reducing bleeding risks while providing similar ischemic protection. Yet, these studies were either prematurely terminated or used non-standard dosages, leaving a gap in understanding the role of newer agents like edoxaban. The EPIC-CAD trial, therefore, aimed to provide more definitive evidence for clinicians, particularly in stable CAD patients with AF who are beyond the initial high-risk period following an acute coronary syndrome event and/or revascularization.

The EPIC-CAD trial was a multicenter, open-label, randomized controlled trial that enrolled 1,040 patients with AF and stable CAD from 18 sites across South Korea (mean age of 72.1 years, 22.9% women, mean CHA₂DS₂-VASc score of 4.3, mean HAS-BLED score of 2.2, and prior coronary revascularization in 65.7%). Patients were randomized to receive either edoxaban monotherapy (60 mg once daily, adjusted for renal function and body weight, N = 524) or dual antithrombotic therapy (edoxaban plus a single antiplatelet agent, N = 516). The primary endpoint was net adverse clinical events, defined as a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding.

The results were striking. At 12 months, the incidence of the primary endpoint was significantly lower in the edoxaban monotherapy group compared to the dual therapy group (6.8% vs. 16.2%, HR 0.44, 95% CI 0.30–0.65, p<0.001). The benefit was driven largely by a reduction in bleeding events, with major bleeding or clinically relevant non-major bleeding occurring in 4.7% of patients on monotherapy versus 14.2% on dual therapy. Importantly, the incidence of ischemic events, including stroke and myocardial infarction, was similar between the two groups, suggesting that monotherapy does not compromise ischemic protection, although the trial was not powered to isolate differences in ischemic outcomes.

For the many patients with both AF and stable CAD, the EPIC-CAD trial provides strong evidence that edoxaban monotherapy can reduce bleeding risk without increasing ischemic events. This aligns with the broader trend in antithrombotic therapy, which seeks to balance thrombotic risk with the dangers of bleeding, particularly in populations at high bleeding risk, such as older patients or those with chronic kidney disease. Importantly, when electing oral anticoagulant monotherapy, careful planning will be needed around the time of elective procedures to ensure adequate bridging protocols that mitigate both ischemic and bleeding risk in the peri-procedural period.

Although EPIC-CAD focused on an East Asian population, the results are consistent with those of other trials, indicating that monotherapy could become a new standard of care for stable CAD patients with AF worldwide. However, further studies may be necessary to confirm these findings in more diverse populations and better understand the long-term implications of monotherapy in patients with vascular diseases beyond coronary artery disease​.

References

Cho MS, Kang DY, Ahn JM, et al. Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease. N Engl J Med. 2024; DOI:10.1056/NEJMoa2407362.