"Edoxaban versus Warfarin in Patients with Atrial Fibrillation". The New England Journal of Medicine. 2013. 369:2093-2104. PubMed • Full text • PDF
Contents
1 Clinical Question
2 Bottom Line
3 Major Points
4 Guidelines
5 Design
6 Population
6.1 Inclusion Criteria
6.2 Exclusion Criteria
6.3 Baseline Characteristics
7 Interventions
8 Outcomes
8.1 Primary Outcomes
8.2 Secondary Outcome
9 Criticisms
10 Funding
11 Further Reading
Clinical Question
In patients with moderate-to-high-risk atrial fibrillation, is edoxaban noninferior or superior to warfarin for the prevention of stroke or systemic embolism?
Bottom Line
In patients with moderate-to-high-risk atrial fibrillation, both high-dose and low-dose regimens of edoxaban were noninferior to warfarin for prevention of stroke or systemic embolism, with significantly lower rates of bleeding and death from cardiovascular causes.
Major Points
Edoxaban, an oral direct factor Xa inhibitor, showed noninferiority to warfarin in preventing stroke or systemic embolism among atrial fibrillation patients. High-dose edoxaban showed a trend toward superior efficacy compared to warfarin, while low-dose edoxaban was associated with less bleeding risk.
Guidelines
As of the latest knowledge cut-off, this trial may influence guidelines by providing a new oral anticoagulant option for the management of stroke prevention in atrial fibrillation, especially for patients who have a moderate-to-high risk of stroke.
Design
- Multicenter, double-blind, double-dummy, randomized controlled trial
- N=21,105
- Warfarin (n=7,031), High-dose edoxaban (n=7,036), Low-dose edoxaban (n=7,038)
- Setting: 1393 centers in 46 countries
- Enrollment: 2008-2010
- Mean follow-up: 2.8 years
- Analysis: Intention-to-treat
- Primary outcome: Stroke or systemic embolism
Population
Inclusion Criteria
- Age ≥ 21 years
- Atrial fibrillation documented within 12 months before randomization
- CHADS2 score of 2 or higher
- Anticoagulation therapy planned for duration of the trial
Exclusion Criteria
- Atrial fibrillation due to a reversible disorder
- Estimated creatinine clearance < 30 ml per minute
- High risk of bleeding
- Use of dual antiplatelet therapy or other anticoagulation therapy
- Mitral stenosis or other indications requiring anticoagulation therapy
- Recent acute coronary syndromes, stroke, or inability to adhere to study procedures
Baseline Characteristics
- Demographics and clinical characteristics were well balanced among the three groups.
Interventions
- Patients were randomized to receive either warfarin (INR 2.0-3.0), high-dose edoxaban (60 mg), or low-dose edoxaban (30 mg).
- Dose was halved for patients with creatinine clearance of 30-50 ml per minute, body weight ≤ 60 kg, or concomitant use of potent P-glycoprotein inhibitors.
Outcomes
Primary Outcomes
- High-dose edoxaban showed noninferiority (and trend toward superiority) compared to warfarin (annualized rate 1.18% vs. 1.50%).
- Low-dose edoxaban was noninferior to warfarin (annualized rate 1.61% vs. 1.50%).
Secondary Outcome
- Major bleeding rates were lower with high-dose edoxaban (2.75%) and low-dose edoxaban (1.61%) compared to warfarin (3.43%).
- Death rates from cardiovascular causes were lower with both doses of edoxaban than with warfarin.
Criticisms
- No specific antidote for edoxaban is available.
- Direct comparative studies are needed to determine real clinical differences compared to other new anticoagulants.
Funding
- Supported by Daiichi Sankyo Pharma Development.
Further Reading
- Full text of the original article in The New England Journal of Medicine.