"Dabigatran versus Warfarin in Patients with Atrial Fibrillation". The New England Journal of Medicine. 2009. 361(12):1139-1151. PubMed • Full text • PDF

Clinical Question

In patients with atrial fibrillation and a risk of stroke, does dabigatran produce similar or better outcomes compared to warfarin?

Bottom Line

In patients with atrial fibrillation, dabigatran at a dose of 110 mg had similar rates of stroke and systemic embolism as warfarin, with lower rates of major hemorrhage. Dabigatran at 150 mg reduced the rates of stroke and systemic embolism compared with warfarin, with similar rates of major hemorrhage.

Major Points

Guidelines

As of the knowledge cut-off date, various guidelines have adopted dabigatran as a therapeutic option for stroke prevention in non-valvular atrial fibrillation, typically providing it as an alternative to warfarin and other newer oral anticoagulants.

Design

Multicenter, randomized, noninferiority and superiority trial
N=18,113 patients with atrial fibrillation and risk of stroke
Dabigatran 110 mg (n=6015), dabigatran 150 mg (n=6076), and warfarin (n=6022)
Median follow-up: 2.0 years
Primary outcome: Stroke or systemic embolism

Population

Inclusion Criteria:
- Atrial fibrillation and ≥1 stroke risk factors
Exclusion Criteria:
- Severe valve disorders, recent stroke, high bleeding risk, creatinine clearance <30 mL/min, or liver disease
Baseline Characteristics
- Mean age of 71 years
- 63.6% male
- Prior vitamin K antagonist therapy: 50%
- Mean CHADS2 score: 2.1

Interventions

- Dabigatran 110 mg or 150 mg, twice daily, double-blind
- Warfarin, targeted INR of 2.0-3.0, unblinded

Outcomes

Primary Outcome: Stroke or systemic embolism
- Dabigatran 110 mg: 1.53% per year
- Dabigatran 150 mg: 1.11% per year (superior to warfarin)
- Warfarin: 1.69% per year

Secondary Outcomes:
- Major bleeding: Lower with dabigatran 110 mg, similar with 150 mg compared to warfarin
- Hemorrhagic stroke: Lower with both dabigatran doses
- Myocardial infarction: Higher with dabigatran

Criticisms

- Open-label nature for warfarin may have introduced bias
- Higher rates of MI and gastrointestinal bleeding with dabigatran, particularly the 150 mg dose
- Variable quality of INR control across different centers

Funding

Boehringer Ingelheim (manufacturer of dabigatran)

Further Reading

Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus Warfarin in Patients with Atrial Fibrillation. N Engl J Med. 2009;361(12):1139-1151. doi:10.1056/NEJMoa0905561.