Level 1: Likely reliable evidence

The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial compared the efficacy and safety of dabigatran (Pradax in Canada and Pradaxa in Europe), a new oral direct thrombin inhibitor that does not require blood test monitoring, with warfarin (Coumadin) in 18,113 patients who had atrial fibrillation and additional risk factors for stroke. Patients were randomized to dabigatran 110 mg or 150 mg twice daily vs. warfarin and followed for median two years. The higher dose of dabigatran was associated with greater efficacy and similar bleeding risk as warfarin, and the lower dose was associated with similar efficacy and lower bleeding risk. Dabigatran 150 mg compared with warfarin reduced the composite primary outcome of stroke or systemic embolism (2.2% vs. 3.3%,P <.001, NNT 91) and vascular mortality (4.5% vs. 5.3%, P =.04, NNT 125), with no significant difference in the risk of major bleeding (5.3% vs. 6.2%). The lower dose of dabigatran vs. warfarin reduced risk of major bleeding (5.4% vs. 6.2%, P =.003, NNT 125) and had a similar rate of stroke or systemic embolism (3% vs. 3.3%) (N Engl J Med. 2009; online ahead of print. Available at content nejm.org/cgi/content/full/NEJMoa0905561v1, accessed September 14, 2009). Dabigatran is currently in phase 3 trials in the United States.