Dabigatran Wins FDA Nod for Stroke Prevention in Afib Patients

MedpageToday

WASHINGTON -- The anticoagulant drug dabigatran (Pradaxa) was cleared for market for preventing strokes and thrombosis in patients with atrial fibrillation, the FDA announced late Tuesday.

The decision was widely expected after a unanimous advisory committee vote last month in favor of approval.

An FDA official noted in a statement announcing the approval that dabigatran, an orally active direct thrombin inhibitor, does not require regular monitoring of patients' coagulation status -- unlike the current standard of care, warfarin (Coumadin).

Key to the approval was an 18,000-person, randomized, noninferiority trial called RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy), which compared unblinded warfarin administration with blinded administration of two doses of dabigatran (110 mg and 150 mg).

A year ago, the RE-LY investigators reported that a 150-mg dose of dabigatran twice daily was more effective in preventing strokes in high-risk patients than warfarin, while a lower dose -- 110 mg -- was comparable to warfarin.

Compared with warfarin-treated subjects, the hazard ratio was 0.66 (with a 95% CI from 0.53 to 0.82; P<0.003 for superiority) in the dabigatran 150-mg arm, and 0.91 (with a 95% CI from 0.74 to 1.11; P<0.0001 for noninferiority) in the dabigatran 110-mg arm.

The trial also found that the bleeding risk with the lower dose of dabigatran was less than in the warfarin group, while bleeding event rates were about the same as warfarin in the high-dose dabigatran patients.

A recent subset analysis of RE-LY data suggested that dabigatran may be especially helpful in patients treated at centers which have a poor track record of maintaining patients at target INR levels -- international normalized ratio levels -- that indicate susceptibility to bleeding and thrombosis.

The FDA nevertheless highlighted bleeding -- including fatal and potentially fatal events -- as the most important adverse side effect of dabigatran.

A medication guide informing patients about the bleeding risks must be distributed with the drug, the FDA ordered.

The drug, manufactured by Boehringer Ingelheim, will be available in 75- and 150-mg capsules.

Atrial fibrillation affects an estimated two million-plus Americans. The condition puts them at increased risk of thrombosis and cerebrovascular ischemic events.