De RE-LY-studie: dabigatran vergeleken met warfarine bij AF

Dabigatran versus Warfarin in Patients with Atrial Fibrillation

Connolly SJ, Ezekowitz MD, et al; RE-LY Steering Committee and Investigators.
N Engl J Med. 2009;361:1139-51..

Samenvatting

Warfarine reduceert stroke bij patiënten met atriumfibrilleren, maar is lastig in gebruik. Daarom wordt een alternatief gezocht.
Dabigatran etexilaat is een prodrug die snel wordt omgezet in dabigatran.
In de RE-LY studie werden twee doseringen vergeleken met warfarine in patiënten met AF en risico voor het krijgen van stroke.
Met de 110 mg dosering trad evenveel stroke op als met warfarine, met significant minder grote bloedingen. Met de 150 mg dosering werd het risico op stroke significant verminderd t.o.v. warfarine, met een gelijk risico op grote bloedingen. Beide doseringen gaven een aanzienlijke reductie in intracraniële bloedingen; beide doses geven geen levertoxiciteit of andere belangrijke toxiciteit.

Abstract

Background:
Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use. Dabigatran is a new oral direct thrombin inhibitor.

Methods:
 In this noninferiority trial, we randomly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive, in a blinded fashion, fixed doses of dabigatran--110 mg or 150 mg twice daily--or, in an unblinded fashion, adjusted-dose warfarin. The median duration of the follow-up period was 2.0 years. The primary outcome was stroke or systemic embolism.

Results:
Rates of the primary outcome were 1.69% per year in the warfarin group, as compared with 1.53% per year in the group that received 110 mg of dabigatran (relative risk with dabigatran, 0.91; 95% confidence interval [CI], 0.74 to 1.11; P<0.001 for noninferiority) and 1.11% per year in the group that received 150 mg of dabigatran (relative risk, 0.66; 95% CI, 0.53 to 0.82; P<0.001 for superiority). The rate of major bleeding was 3.36% per year in the warfarin group, as compared with 2.71% per year in the group receiving 110 mg of dabigatran (P=0.003) and 3.11% per year in the group receiving 150 mg of dabigatran (P=0.31). The rate of hemorrhagic stroke was 0.38% per year in the warfarin group, as compared with 0.12% per year with 110 mg of dabigatran (P<0.001) and 0.10% per year with 150 mg of dabigatran (P<0.001). The mortality rate was 4.13% per year in the warfarin group, as compared with 3.75% per year with 110 mg of dabigatran (P=0.13) and 3.64% per year with 150 mg of dabigatran (P=0.051).

Conclusions:
In patients with atrial fibrillation, dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. 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.