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Evevident
Original paper
2009NEJMCardiology

RE-LY

Dabigatran versus warfarin in patients with atrial fibrillation

RCTAtrial fibrillation

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Overview

Dabigatran provided effective stroke prevention in AF: 150 mg BID reduced stroke/systemic embolism versus warfarin, while 110 mg BID had less major bleeding with similar efficacy.

Clinical takeaway

RE-LY helped launch DOACs as alternatives to warfarin for nonvalvular AF, trading INR monitoring for renal dosing and drug-specific bleeding considerations.

Key result

Dabigatran 150 mg reduced stroke/systemic embolism versus warfarin (RR 0.66; 95% CI 0.53-0.82).

Practice impact

DOACs became first-line anticoagulation for many nonvalvular AF patients.

Evidence

Study design

Randomized trial with blinded dabigatran doses and open-label warfarin.

Enrollment

18,113

Follow-up

Median 2.0 years.

Geography

Multinational

Clinical question

Is dabigatran noninferior or superior to warfarin for preventing stroke/systemic embolism in AF?

Population

  • Patients with nonvalvular atrial fibrillation and at least one additional risk factor for stroke.

Intervention

Dabigatran 110 mg or 150 mg twice daily.

Comparator

Dose-adjusted warfarin (target INR 2.0-3.0).

Primary outcome

Stroke or systemic embolism.

Dabigatran 150 mg twice daily was superior to warfarin for preventing stroke or systemic embolism, with similar major bleeding.

Relative risk / 0.66 / CI 95% CI 0.53-0.82 / p=<0.001

Key results

  • Stroke or systemic embolism: 1.11%/yr with dabigatran 150 mg vs 1.69%/yr with warfarin; RR 0.66; 95% CI 0.53-0.82; p<0.001 for superiority.
  • Dabigatran 110 mg was noninferior (1.53%/yr; RR 0.91; 95% CI 0.74-1.11) with lower major bleeding than warfarin (2.71%/yr vs 3.36%/yr; p=0.003).
  • Major bleeding with dabigatran 150 mg was similar to warfarin (3.11%/yr vs 3.36%/yr; p=0.31).
  • Hemorrhagic stroke was markedly lower with both dabigatran doses (0.10-0.12%/yr vs 0.38%/yr; p<0.001).

Harms

  • Dabigatran caused more dyspepsia and gastrointestinal symptoms than warfarin.
  • Gastrointestinal major bleeding was higher with dabigatran 150 mg than with warfarin.
  • There was a nonsignificant trend toward more myocardial infarction with dabigatran.

Clinical Use

When to cite

  • When discussing dabigatran and the early evidence that DOACs can replace warfarin for many patients with nonvalvular AF.

Practice impact

  • DOACs became first-line anticoagulation for many nonvalvular AF patients.

Applicability

  • Most applicable to patients with nonvalvular atrial fibrillation and at least one additional stroke risk factor.

Limitations

  • Open-label warfarin arm.
  • Renal clearance limits use in advanced CKD, and there is no simple INR-style monitoring.
  • Not for mechanical heart valves or moderate-to-severe mitral stenosis.

Common misinterpretations

  • Do not use dabigatran for mechanical valves; RE-ALIGN later showed net harm in that setting.
  • The 110 mg dose was not approved in the United States, where 150 mg and a renally adjusted 75 mg dose are used.

Related evidence

ARISTOTLE - Same Drug Class

Citation

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

Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage.