NEW YORK (Reuters Health) – Dabigatran (Pradaxa, Boehringer Ingelheim) is as effective as warfarin in preventing stroke and systemic embolism after cardioversion in patients with nonvalvular atrial fibrillation, according to a post-hoc analysis of the RE-LY trial.

The original results of the multinational Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial showed that the direct thrombin inhibitor dabigatran is at least as effective as warfarin in patients with atrial fibrillation. (See Reuters Health article of August 31, 2009.)

Approved for preventing stroke during atrial fibrillation by the U.S. Food and Drug Administration in October last year, dabigatran holds many advantages over warfarin: It is orally available with reversible effects and a rapid onset of action (peak plasma concentration within 2 hours and a half-life of 12 to 17 hours). Dosed twice daily, it doesn’t require INR monitoring.

However, dabigatran’s cost is more than ten times that of warfarin. Lead author Dr. Rangadham Nagarakanti, from the Louisiana State University School of Medicine in New Orleans, and co-investigators suggest that dabigatran may prove economical by avoiding hospitalization.

The original RE-LY trial included more than 18,000 subjects, of whom 1270 underwent a total of 1983 cardioversions during the study (647 randomly assigned to dabigatran 110 mg twice daily, 672 to dabigatran 150 mg twice daily, and 664 to warfarin dosed to maintain an INR of 2.0 to 3.0). Clinicians administered study drugs for at least 3 weeks before cardioversion, then maintained them afterward.

Results appear in Circulation published online January 3rd.

During the 30 days post-cardioversion, rates of stroke and systemic embolic events were 0.77% in the low-dose dabigatran group, 0.30% in the high-dose dabigatran group, and 0.60% in the warfarin group, which did not differ significantly. Rates of major bleeding over the same period were 1.7%, 0.6%, and 0.6%, respectively.

Outcomes followed a similar pattern in a separate analysis for first cardioversions of each patient.

Based on this noninferiority trial – the largest study of atrial fibrillation patients undergoing cardioversion – Dr. Nagarakanti’s group concludes that dabigatran is a reasonable alternative to warfarin.

The study was funded by a grant from Boehringer Ingelheim. Eight authors report having received funding from the pharmaceutical company, and one author is its employee.

Reference:

Dabigatran Versus Warfarin in Patients With Atrial Fibrillation


Circulation 2011.