Impact of renal function on edoxaban antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease: a prespecified analysis of the EPIC-CAD trial
Clinical Snapshot
PICO Framework
| P — Population | Patients with atrial fibrillation and stable coronary artery disease, stratified by renal function (creatinine clearance <50 mL/min vs ≥50 mL/min) |
| I — Intervention | Edoxaban monotherapy |
| C — Comparator | Dual antithrombotic therapy (edoxaban plus single antiplatelet agent) |
| O — Outcomes | Net adverse clinical events (NACE) at 12 months: death, myocardial infarction, stroke, systemic embolism, urgent revascularisation, or major/clinically relevant non-major bleeding |
Bottom Line
This prespecified subgroup analysis of the EPIC-CAD trial demonstrates that edoxaban monotherapy is superior to dual antithrombotic therapy (edoxaban plus antiplatelet) in patients with atrial fibrillation and stable coronary artery disease, regardless of renal function. The benefit was consistent across both low (<50 mL/min) and high (≥50 mL/min) creatinine clearance groups, with number needed to treat of approximately 10-11 patients. Patients with impaired renal function had higher baseline risks but derived similar relative benefit from monotherapy. This evidence supports a simplified antithrombotic approach in stable CAD patients with AF, potentially reducing bleeding complications while maintaining ischaemic protection. However, the baseline imbalance between renal function groups and limited methodological details in this abstract warrant cautious interpretation. The findings align with contemporary guidelines favouring risk-stratified antithrombotic therapy and support edoxaban monotherapy as a reasonable strategy in this high-risk population.
Key Findings
P Value: Low CrCl: p=0.042; High CrCl: p<0.001; Interaction p=0.53
Effect Size: Low CrCl: HR 0.52 (edoxaban mono vs dual); High CrCl: HR 0.40 (edoxaban mono vs dual)
Primary Outcome: Net adverse clinical events (NACE) at 12 months
Nnt Or Sensitivity: NNT approximately 10-11 patients (based on absolute risk differences of 9.3-9.6%)
Confidence Interval: Low CrCl: 95% CI 0.28-0.98; High CrCl: 95% CI 0.25-0.65
Clinical Application
Highly feasible - edoxaban is PBS-listed for AF, and monotherapy simplifies management while reducing bleeding risk Relevant to Australian practice where edoxaban is PBS-subsidised for AF. Supports RACGP and CSANZ guidelines emphasising individualised antithrombotic therapy based on bleeding risk assessment Patients with atrial fibrillation and stable coronary artery disease, particularly those with impaired renal function requiring careful antithrombotic management
Abstract
BACKGROUND: Renal function is a critical factor of ischaemic and bleeding risks in patients with atrial fibrillation (AF) receiving antithrombotic therapy. AIMS: This study aimed to evaluate the impact of renal dysfunction in patients with AF and stable coronary artery disease (CAD) undergoing antithrombotic therapy. METHODS: The Edoxaban Versus Edoxaban With antiPlatelet Agent In Patients With Atrial Fibrillation and Chronic Stable Coronary Artery Disease (EPIC-CAD) trial randomised patients to edoxaban monotherapy or dual antithrombotic therapy (edoxaban plus a single antiplatelet agent). In this prespecified analysis, patients were stratified by creatinine clearance into low (<50 mL/min) or high (≥50 mL/min) groups according to edoxaban dose-reduction criteria. The primary endpoint was net adverse clinical events (NACE: death from any cause, myocardial infarction, stroke, systemic embolism, urgent revascularisation, or major/clinically relevant non-major bleeding) at 12 months. RESULTS: Of 1,040 randomised patients, 252 (24.2%) had low creatinine clearance; these patients were older and had more comorbidities compared with the 788 patients (75.8%) with high creatinine clearance. Patients with low creatinine clearance experienced higher risks of NACE (hazard ratio [HR] 1.72, 95% confidence interval [CI]: 1.19-2.49; p=0.004), ischaemic events (HR 2.70, 95% CI: 1.09-6.70; p=0.032), and bleeding (HR 1.54, 95% CI: 1.01-2.34; p=0.046). At 12 months, edoxaban monotherapy reduced NACE compared with dual therapy in both the low (12.1% vs 21.7%, HR 0.52, 95% CI: 0.28-0.98; p=0.042) and high creatinine clearance groups (5.2% vs 14.5%, HR 0.40, 95% CI: 0.25-0.65; p<0.001), with no interaction (p for interaction=0.53). CONCLUSIONS: In patients with AF and stable CAD, edoxaban monotherapy led to a lower risk of primary NACE than dual antithrombotic therapy, regardless of renal function. (ClinicalTrials.gov: NCT03718559).
References
- 1.Lee, J. M., Cho, M. S., Kang, D. Y., Ahn, J. M., 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., 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 renal function on edoxaban antithrombotic therapy in patients with atrial fibrillation and stable coronary artery disease: A prespecified analysis of the EPIC-CAD trial. EuroIntervention, Article EIJ-D-25-01274. https://doi.org/10.4244/EIJ-D-25-01274
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