Dabigatran gets approval from FDA

One of cardiology's fondest wishes moved closer to fulfillment as an FDA advisory panel unanimously recommended approval of a potential replacement for warfarin in one of the most common heart disorders. Barring any unforeseen damning revelations about the drug, the FDA's approval of the oral thrombin inhibitor dabigatran (Pradaxa, Boehringer Ingelheim) for stroke prevention in atrial fibrillation (AF) is all but certain.

The panel, with its nine voting members, made the decision based on what's generally seen as the well-designed, solidly executed 18 000-patient Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY) trial, which showed dabigatran was noninferior to warfarin at a lower dosage and superior at a higher one for preventing thromboembolic stroke in paroxysmal or permanent AF.

Debate among the advisory panel throughout the day was tame; there were few criticisms of the RE-LY trial's design, little disappointment in the results, and clear enthusiasm for replacing warfarin in such a widespread indication.

Warfarin is distinguished in being one of the oldest, one of the most widely used, one of the most effective, and one of the most disliked drugs in cardiology: it dramatically cuts ischemic stroke risk in AF but generally requires tight anticoagulation monitoring to get the dosage right, which can be arduous for patients and the healthcare system. Patients must also banish a lot of healthy, vitamin-K-containing foods from their diet.

The kicker with dabigatran, even when "noninferior" to warfarin, is that it doesn't require anticoagulation monitoring—or major diet changes, for that matter. And, as the trial suggested and some panelists agreed, at the higher dose it seems more stroke-preventive than warfarin.

RE-LY compared the two dabigatran dosage levels against a conventional warfarin regimen for the stroke-prevention indication. Dabigatran was noninferior to warfarin at the lower dosage and superior at the higher one, the latter achieving a 34% decline in risk (p<0.001) over a median of two years.