EPIC-CAD
Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease
Clinical Question
Is edoxaban monotherapy safer and non-inferior to dual antithrombotic therapy (edoxaban plus antiplatelet) in patients with atrial fibrillation and stable coronary artery disease?
Bottom Line
Edoxaban monotherapy reduced bleeding and net adverse clinical events compared to edoxaban plus single antiplatelet therapy in patients with AF and stable CAD, without increasing ischemic risk.
Major Points
- Multicenter, randomized trial (N=1040) comparing edoxaban monotherapy versus edoxaban plus single antiplatelet therapy in AF patients with stable CAD.
- Primary outcome occurred in 6.8% of monotherapy group vs. 16.2% in dual therapy group (HR 0.44; 95% CI, 0.30–0.65; P<0.001).
- Major or clinically relevant nonmajor bleeding significantly lower with monotherapy (4.7% vs. 14.2%; HR 0.34).
- Rates of major ischemic events were similar (1.6% vs. 1.8%; HR 1.23; not significant).
- Results consistent across prespecified subgroups and in per-protocol analyses.
Design
Study Type: Multicenter, open-label, adjudicator-blinded, randomized controlled trial
Randomization: 1
Blinding: Blinded outcome adjudication only
Enrollment Period: May 2019 – September 2022
Follow-up Duration: 12 months
Centers: 18
Countries: South Korea
Sample Size: 1040
Analysis: Intention-to-treat and per-protocol; Kaplan–Meier survival analysis, Cox regression
Inclusion Criteria
- Age ≥18 years with paroxysmal or persistent atrial fibrillation
- Stable coronary artery disease (≥6 months after PCI/CABG or medically managed)
- CHA2DS2-VASc score ≥2
Exclusion Criteria
- High bleeding risk
- History of intracranial hemorrhage
- Mechanical heart valves or moderate-to-severe mitral stenosis
- Severe renal (CrCl <15 ml/min) or hepatic dysfunction
- Planned PCI or CABG within 12 months
- Life expectancy <12 months
Arms
| Field | Edoxaban Monotherapy | Control |
|---|---|---|
| Intervention | Edoxaban 60 mg daily (30 mg if dose-adjusted for renal function, weight, or drug interactions) | Edoxaban 60 mg (or 30 mg adjusted) plus aspirin or P2Y12 inhibitor (per physician discretion) |
| Duration | 12 months | 12 months |
Outcomes
| Outcome | Type | Control | Intervention | HR / OR / RR | P-value |
|---|---|---|---|---|---|
| Composite of death, myocardial infarction, stroke, systemic embolism, urgent revascularization, or ISTH major or clinically relevant nonmajor bleeding | Primary | 16.2% | 6.8% | 0.44 | <0.001 |
| Major ischemic events (death, MI, stroke, or systemic embolism) | Secondary | 1.8% | 1.6% | 1.23 | 0.64 |
| Major bleeding or clinically relevant nonmajor bleeding | Secondary | 14.2% | 4.7% | 0.34 | <0.001 |
| Any bleeding | Secondary | 20.1% | 9.9% | 0.48 | <0.001 |
| Major bleeding | Adverse | 4.5% | 1.3% | ||
| CRNM bleeding | Adverse | 10.6% | 3.5% | ||
| ICH | Adverse | 0.6% | 0.4% | ||
| GI bleeding | Adverse | 2.6% | 1.6% |
Subgroup Analysis
No significant heterogeneity across prespecified subgroups including age, sex, renal function, AF type, and revascularization status
Criticisms
- Open-label design may introduce bias despite blinded outcome adjudication
- Not powered to detect differences in rare ischemic events
- Limited generalizability to non-Asian populations or those early post-PCI
- Underrepresentation of women (22.9%)
Funding
CardioVascular Research Foundation; supported by grants from Daiichi Sankyo and Daewoong Pharmaceutical
Based on: EPIC-CAD (New England Journal of Medicine, 2024)
Authors: M.S. Cho, D.-Y. Kang, J.-M. Ahn, ..., G.-M. Park
Citation: N Engl J Med 2024;391:2075–2086. DOI: 10.1056/NEJMoa2407362
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