ENGAGE AF-TIMI 48 (edoxaban 60 mg)
Trial question
Is edoxaban noninferior to warfarin in patients with AF?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
38.0% female
62.0% male
N = 14071
14071 patients (5310 female, 8761 male).
Inclusion criteria: patients with AF at moderate-to-high AF risk.
Key exclusion criteria: AF due to a reversible disorder; high risk of bleeding; use of dual antiplatelet therapy; moderate-to-severe MS; other indications for anticoagulation therapy; acute coronary syndromes, coronary revascularization, or stroke in the past 30 days.
Interventions
N=7035 high-dose edoxaban (60 mg/day).
N=7036 warfarin (dose-adjusted to achieve an INR of 2.0-3.0).
Primary outcome
Stroke or systemic embolic events
1.18%
1.5%
1.5 %
1.1 %
0.8 %
0.4 %
0.0 %
High-dose
edoxaban
Warfarin
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in stroke or systemic embolic events (1.18% vs. 1.5%; HR 0.79, 97.5% CI 0.63 to 0.99).
Secondary outcomes
Significant decrease in stroke, systemic embolism, or CV death (3.85% vs. 4.43%; HR 0.87, 95% CI 0.78 to 0.96).
Significant decrease in CV death (2.74% vs. 3.17%; HR 0.86, 95% CI 0.77 to 0.97).
No significant difference in MI (0.7% vs. 0.75%; HR 0.94, 95% CI 0.74 to 1.19).
Safety outcomes
No significant difference in stroke and systemic embolic events.
Significant difference in major bleeding events (2.75% vs. 3.43%).
Conclusion
In patients with AF at moderate-to-high AF risk, high-dose edoxaban was noninferior to warfarin with respect to stroke or systemic embolic events.
Reference
Giugliano RP, Ruff CT, Braunwald E et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013 Nov 28;369(22):2093-104.
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