Impact of Atrial Fibrillation Pattern on Edoxaban Antithrombotic Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease: A Secondary Analysis of the EPIC-CAD Randomized Clinical Trial

Clinical Snapshot

Key Findings

• P Value: P for interaction = 0.10 (non-significant)

• Effect Size: Edoxaban monotherapy vs dual therapy - Paroxysmal AF: HR 0.23; Nonparoxysmal AF: HR 0.56

• Primary Outcome: Net adverse clinical events at 12 months: paroxysmal AF 10.3% vs nonparoxysmal AF 12.2%

• Nnt Or Sensitivity: NNT approximately 9 for paroxysmal AF (11.6% absolute risk reduction) and 18 for nonparoxysmal AF (5.7% absolute risk reduction)

• Confidence Interval: Paroxysmal AF: 95% CI 0.12-0.42; Nonparoxysmal AF: 95% CI 0.32-0.87

Clinical Application

Highly feasible - edoxaban is PBS-listed for AF stroke prevention, and monotherapy approach simplifies medication regimens Aligns with RACGP and CSANZ guidelines favouring simplified anticoagulation strategies. Edoxaban PBS listing supports cost-effective implementation. May reduce polypharmacy burden in elderly Australian AF patients Australian patients with atrial fibrillation and stable coronary artery disease, particularly those >12 months post-PCI or with established stable CAD

Abstract

BACKGROUND: Paroxysmal atrial fibrillation (AF) is associated with a risk of stroke or systemic embolism similar to nonparoxysmal (persistent or permanent) AF. However, whether the optimal antithrombotic strategy in patients with AF and stable coronary artery disease differs by AF pattern remains uncertain. METHODS: This prespecified substudy of the EPIC-CAD (Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease) trial compared edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with AF and stable coronary artery disease. Stratified analyses were performed by AF pattern. The primary outcome was net adverse clinical events, defined as a composite of all-cause death, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, major bleeding, or clinically relevant nonmajor bleeding within 12 months. RESULTS: Among 1040 patients, 575 (55.3%) had paroxysmal and 465 (44.7%) had nonparoxysmal AF. The 12-month primary outcome rate was similar between paroxysmal and nonparoxysmal AF (10.3% versus 12.2%; adjusted hazard ratio [HR], 1.15 [95% CI, 0.79-1.68]). Edoxaban monotherapy was associated with a significantly lower risk of the primary outcome than dual antithrombotic therapy in both paroxysmal AF (4.6% versus 16.2%; adjusted HR, 0.23 [95% CI, 0.12-0.42]) and nonparoxysmal AF (9.3% versus 15.0%; adjusted HR, 0.56 [95% CI, 0.32-0.87]). No significant interaction was observed between antithrombotic strategy and AF pattern (P for interaction=0.10). CONCLUSIONS: In patients with AF and stable coronary artery disease, edoxaban monotherapy significantly reduced net adverse clinical events at 12 months compared with dual antithrombotic therapy, irrespective of AF pattern. REGISTRATION: URL: https://www.ClinicalTrials.gov; Unique identifier: NCT03718559.

References

1. 1.Yu, J. S., Cho, M. S., Kang, D. Y., Ahn, J. M., Lee, J. B., Oh, Y. S., Lee, C. H., Choi, E. K., Lee, J. H., Kwon, C. H., Park, G. M., Choi, H. O., Park, K. H., Park, K. M., Hwang, J. M., Yoo, K. D., Cho, Y. R., Kim, J. H., Hwang, K. W., Jin, E. S., Kwon, O., Kim, K. H., Park, S. J., Nam, G. B., & Park, D. W. (2026). Impact of Atrial Fibrillation Pattern on Edoxaban Antithrombotic Therapy in Patients With Atrial Fibrillation and Stable Coronary Artery Disease: A Secondary Analysis of the EPIC-CAD Randomized Clinical Trial. Journal of the American Heart Association. https://doi.org/10.1161/JAHA.125.046966