The advisory panel for the US Food and Drug Administration (FDA) voted unanimously on September 20 to recommend approval of dabigatran, an anticoagulant under investigation for the reduction of stroke risk and non-CNS systemic embolism in patients with atrial fibrillation.
The advisory board only voted that dabigatran works at least as well as warfarin. But unlike warfarin, dabigatran does not require laboratory monitoring. Therefore, dabigatran is less difficult to use than the current standard of care.
The decision was based on the randomized, noninferiority RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial of 18,000 patients. The trial compared unblinded warfarin administration with blinded doses of dabigatran at 110 mg and 150 mg.
The hazard ratio of dabigatran compared with warfarin was 0.66 (P<0.003) in the 150 mg dabigatran arm and 0.91 (P<0.0001) in the 110 mg dabigatran arm.
Bleeding risk remains the top safety concern. Receiving 150 mg of dabigatran seems to run the same risk as warfarin for bleeding complications, but in 110 mg doses of dabigatran, the risk was less than warfarin.
Conflict arose among committee members regarding whether or not to approve both doses. Some members disagreed, seeing that the 110 mg dose was only noninferior to warfarin, not superior. Other members believed that approving both doses would ensure wider use of the drug leading to the prevention of a greater number of strokes in atrial fibrillation patients.
There is one unexplained finding of the RE-LY study. Myocardial infarction rates were higher on dabigatran compared with warfarin. For every 1000 patients treated with dabigatran, there may be 2 more myocardial infarctions than in patients treated with warfarin.
The FDA often follows the advice of the panel of experts, although it is not required to.
