Dabigatran an Alternative to Warfarin for Stroke Prevention in A-Fib Patients
BARCELONA, Spain—In patients with atrial fibrillation, 2 doses of the reversible, direct thrombin inhibitor dabigatran show similar or better effectiveness than warfarin in preventing stroke and systemic embolism, with equal or lower risk of major bleeding, according to late breaking trial results presented August 30 at the European Society of Cardiology (ESC) Congress 2009. The findings were simultaneously published online in the New England Journal of Medicine.
For the noninferiority RE-LY (Randomized Evaluation of Long-term anticoagulant therapY) trial, researchers led by Stuart J. Connolly, MD, of McMaster University (Hamilton, Canada), compared 2 doses of dabigatran (110 or 150 mg twice daily) with warfarin (adjusted dose) in 18,113 patients at 951 centers who were at risk of stroke from atrial fibrillation. Aspirin was used continuously by about one fifth of patients in all 3 arms.
Dabigatran etexilate (Pradaxa, Boehringer-Ingelhiem Pharmaceuticals, Ridgfield, CT) is approved in Europe for the prevention of venous thromboembolism.
Dose Makes a Difference
After a median follow-up of 2 years, both doses of dabigatran proved noninferior to warfarin with regard to the primary endpoint of stroke or systemic embolism. However, the 150-mg dose of dabigatran was superior to warfarin (P < 0.001), whereas the 110-mg dose was not (P = 0.34). Rates of hemorrhagic stroke were lower with both doses of dabigatran, but MI rates were higher with each dose, reaching significance at 150 mg. Dabigatran was comparable with warfarin with regard to mortality, although there was a trend toward improved survival with 150-mg dabigatran (tables 1 and 2).
Table 1. Efficacy Outcomes (Per Year) for Lower-Dose Dabigatran vs. Warfarin
Table 3. Safety Outcomes (Per Year) for Lower-Dose Dabigatran vs. Warfarin
Overall, the net clinical benefit outcome, which combines major vascular events, major bleeding, and death, favored dabigatran over warfarin and was similar for the 2 doses.
Success Raises Questions
A.J. Camm, MD, of St. George’s Hospital Medical School (London, United Kingdom), said that the dabigatran results raised a number of questions, such as:
Dr. Camm recommended that dabigatran be considered a “stimulant to a paradigm change in the development of anticoagulant medications,” but that the study results should “not be allowed to derail trials of other agents.”
All 3 treatment groups were well balanced with regard to baseline characteristics. Their mean CHADS2 score was 2.1. About half had received long-term therapy with a vitamin K antagonist.
Connolly SJ. The RE-LY Study: Randomized Evaluation of Long-term anticoagulation therapY. Dabigatran compared to warfarin in 18,113 patients with atrial fibrillation at risk of stroke. Presented at: ESC Congress 2009; August 30, 2009; Barcelona, Spain.
Connolly SJ, Ezekowitz MD, Yusuf F, et al. Dabigatran versus warfarin. N Engl J Med 2009;Epub ahead of print.
- The study was supported by a grant from Boehringer-Ingelheim.
- The study was supported by a grant from Boehringer-Ingelheim. Dr. Connolly reports receiving consulting fees, lecture fees, and grants from Boehringer-Ingelheim
- Information regarding any potential conflicts of interest for Dr. Camm was not available.