← Back

EPIC-CAD

Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease

Share Share Copied! Compare

Year of Publication: 2024

Authors: M.S. Cho, D.-Y. Kang, J.-M. Ahn, ..., G.-M. Park

Journal: New England Journal of Medicine

Citation: N Engl J Med 2024;391:2075–2086. DOI: 10.1056/NEJMoa2407362

Link: https://www.nejm.org/doi/full/10.1056/NEJMoa2407362

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

Content summarized and formatted by NeuroTrials.ai.

EPIC-CAD

(2024)

Objective

Edoxaban monotherapy versus edoxaban plus single antiplatelet therapy in patients with atrial fibrillation and stable coronary artery disease (CAD) for prevention of ischemic and bleeding events.

Study Summary

• In patients with AF and stable CAD, edoxaban monotherapy significantly reduced the composite outcome of ischemic and bleeding events compared to dual therapy (edoxaban plus anti-platelet agent).

Intervention

Edoxaban 60 mg daily (or 30 mg if dose reduction criteria met) alone vs. Edoxaban plus a single antiplatelet agent (aspirin or clopidogrel).

Inclusion Criteria

Patients ≥18 years with paroxysmal or persistent AF, CHA₂DS₂-VASc ≥2, and stable CAD (≥6 months post-PCI/CABG or ≥12 months post-ACS, or ≥50% stenosis managed medically).

Study Design

Arms: Edoxaban Monotherapy vs. Edoxaban + Single Antiplatelet Agent

Patients per Arm: Monotherapy: 524, Dual Therapy: 516

Outcome

• Primary net adverse clinical events: 6.8% vs. 16.2% (HR 0.44; P<0.001). • Major bleeding or CRNM bleeding: 4.7% vs. 14.2% (HR 0.34). • Major bleeding: 1.3% vs. 4.5% (HR 0.32). • Any ischemic events: 3.0% vs. 2.4% (HR 1.40). • Stroke: 1.4% vs. 0.8%. • MI: 0% vs. 0.5%. • All-cause death: 0.6% vs. 0.7%. • Stent thrombosis: 0%. • Intracranial hemorrhage: 0.4% vs. 0.6%. • GI bleeding: 1.6% vs. 2.6%.

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.

Study Design

Study Type: Multicenter, open-label, adjudicator-blinded, randomized controlled trial
Randomization: Yes
Blinding: Blinded outcome adjudication only
Sample Size: 1040
Follow-up: 12 months
Centers: 18
Countries: South Korea

Primary Outcome

Definition: Composite of death, myocardial infarction, stroke, systemic embolism, urgent revascularization, or ISTH major or clinically relevant nonmajor bleeding

Control	Intervention	HR/OR	P-value
16.2%	6.8%	0.44 (0.30–0.65)	<0.001

Limitations & 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%)

Citation

N Engl J Med 2024;391:2075–2086. DOI: 10.1056/NEJMoa2407362

View Original Publication →

EPIC-CAD

Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease

Clinical Question

Bottom Line

Major Points

Design

Inclusion Criteria

Exclusion Criteria

Arms

Outcomes

Subgroup Analysis

Criticisms

Funding

Ask about EPIC-CAD