Further information: Atrial Fibrillation and Flutter (see p1955) from Cardiovascular Medicine, 3rd Edn*

Investigators conducted the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial to compare two fixed doses of dabigratran with the open-label use of warfarin in patients who had atrial fibrillation (AF) and were at risk for stroke [1]. In the randomized, noninferiority trial, the blinded, fixed doses of dabigatran administered were 110 mg twice daily or 150 mg twice daily and were compared with unblinded, adjusted-dose warfarin. Primary outcome of the trail was stroke or systemic embolism, and secondary outcomes were stroke, systemic embolism, and death. Between December 2005 and December 15, 2007, 18,113 patients from 951 clinical centers in 44 countries were enrolled into the three treatment groups. A patient’s eligibility included documented AF within 6 months prior to recruitment, and at least one additional characteristic, such as previous stroke or transient ischemic attack, left ventricular ejection fraction (LVEF) less than 40%, NYHA class II or higher heart failure symptoms 6 months prior, and at least 75 years of age. Patients who had diabetes, hypertension, or CAD could be age 65–74. Median follow-up was 2.0 years.

Warfarin is a vitamin K antagonist used in patients with AF to reduce their risk of stroke and death, but it has a primary complication of intracranial hemorrhage. Therefore, results showing that the dose of 150 mg of dabigatran was associated with lower rates of stroke and systemic embolism (primary outcome) were of interest (1.69% per year in warfarin group; 1.53% per year in group who received 110 mg of dabigatran; 1.11% per year in group who received 150 mg of dabigatran). Major bleeding rate was 3.36% per year in warfarin group, 2.71% in the 110 mg dabigatran group, and 3.11% per year in the 150 mg of dabigatran group. Hemorrhagic stroke rate was 0.38% per year for warfarin, 0.12% per year for 110 mg of dabigatran 10% per year for 150 mg of dabigatran.

The investigators concluded that from the data that in comparison with warfarin, dabigatran dosed at 150 mg revealed lower stroke and systemic embolism, but had similar rates of major hemorrhage.

In an accompanying editorial [2], Brian Gage emphasized that while warfarin has been a recommended treatment for AF patients at risk for stroke for some time, the complications in administration of the medication have precluded its use for some patients, and he believes it is necessary to develop new oral anticoagulants. He concludes that in regard to the current study of dabigatran, patients who are currently on a well-controlled INR regimen should stay with warfarin, but patients with AF and an additional risk factor for stroke would benefit from the use of dabigatran. He stated that the 110 mg dose appears safer, the 150 mg dose appears more efficacious, and that while additional studies are needed, patients with AF plus additional risk factors could benefit from its use.

[1] Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation (RE-LY). N Engl J Med 2009;361:1139-1151

[2] Gage BF. Can we rely on RE-LY? N Engl J Med 2009;361:1200-1202

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