PDF: NOAH-AFNET 6
(2023)Objective
Edoxaban versus placebo in patients with device-detected atrial high-rate episodes (AHREs) without ECG-documented atrial fibrillation.
Study Summary
• Edoxaban did not significantly reduce the incidence of cardiovascular death, stroke, or systemic embolism compared to placebo. • However, it was associated with a higher incidence of major bleeding and all-cause mortality. • The overall incidence of stroke was low in both groups. • The trial was stopped early due to futility and safety concerns.
Intervention
Edoxaban 60 mg daily (or 30 mg if dose reduction criteria met) vs. placebo; patients were ≥65 years with AHRE ≥6 minutes and at least one stroke risk factor; median follow-up was 21 months.
Study Design
Arms: Edoxaban vs Placebo
Outcome
• Major bleeding occurred in 2.1% with edoxaban vs. 1.0% with placebo (HR 2.10; 95% CI 1.30–3.38; p=0.002). • Composite safety outcome (death or major bleeding): HR 1.31; p=0.03. • The trial did not demonstrate a benefit in stroke prevention with edoxaban in this population.
Bottom Line
Edoxaban did not significantly reduce cardiovascular death, stroke, or systemic embolism but increased major bleeding risk in patients with AHREs.
Major Points
- Edoxaban showed no statistically significant reduction in primary efficacy outcome (HR 0.81; P=0.15).
- Stroke incidence was low in both groups (~1%/year).
- Major bleeding was significantly higher in the edoxaban group (HR 2.10; P=0.002).
- Trial stopped early due to safety concerns and futility.
- Study included older, high-risk patients (mean age 78, median CHA₂DS₂-VASc score 4).
Study Design
- Study Type
- Randomized, double-blind, placebo-controlled
- Randomization
- Yes
- Blinding
- Double-blind
- Sample Size
- 2536
- Follow-up
- Median 21 months
- Centers
- 206
- Countries
- Austria, Belgium, Bulgaria, Czech Republic, Denmark, France, Germany, Greece, Hungary, Italy, Netherlands, Poland, Portugal, Romania, Spain, Sweden, Ukraine, United Kingdom
Primary Outcome
Definition: Composite of cardiovascular death, stroke, or systemic embolism
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 4.0% per patient-year | 3.2% per patient-year | 0.81 (0.60–1.08) | 0.15 |
Limitations & Criticisms
- Trial stopped early, limiting power to detect modest benefits.
- Stroke rate lower than expected, may reflect low AHRE burden.
- Unclear generalizability to other NOACs beyond edoxaban.
- Predominantly White European population.
Citation
Kirchhof P, et al. N Engl J Med. 2023;389(13):1167–1179.