Anticoagulant Options — Why the FDA Approved a Higher but Not a Lower Dose of Dabigatran for non valvular atrial fibrillation

NEJM | April 13, 2011 | Topics: Drugs, Devices, and the FDA

On October 19, 2010, the Food and Drug Administration (FDA) approved dabigatran for the reduction of the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. Approval was based on a multicenter, active-control trial, the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY), in which patients were randomly assigned to receive 150 mg of dabigatran, 110 mg of dabigatran, or warfarin. Dabigatran was given twice daily; warfarin was titrated to achieve an international normalized ratio (INR) of 2.0 to 3.0. Assignment to warfarin or dabigatran treatment was unblinded; assignment to a specific dabigatran dose was double-blind. RE-LY was a noninferiority study, attempting to rule out a hazard ratio of more than 1.38 for the primary end point, stroke or systemic embolism.