BETHESDA, MD 20 December 2012—FDA today urged health care professionals to promptly transition any patient with a mechanical heart valve who is taking dabigatran etexilate mesylate to another anticoagulant drug.
The agency made the announcement after learning that the sponsor of "The Randomized, phase II study to Evaluate the sAfety and pharmacokinetics of oraL dabIGatran etexilate in patients after heart valve replacemeNt" (RE-ALIGN) had recently stopped it.
FDA said the study was stopped because the patients who used dabigatran etexilate rather than warfarin were more likely to have strokes, heart attacks, and blood clots on the mechanical heart valves.
, which sponsored the study and markets dabigatran etexilate as Pradaxa, said the study was stopped because its interim results suggested that the "investigated dosing regimen did not achieve the desired results in this patient population."
The FDA-approved labeling (PDF) for Pradaxa now lists mechanical prosthetic heart valve as a contraindication.
And the product's medication guide now tells patients not to take the drug if they have ever had or plan to have a heart valve replaced.
According to FDA's summary of the interim data from RE-ALIGN, 10% of dabigatran etexilate users and 4.5% of warfarin users had a stroke, systemic embolism event, transient ischemic attack, valve thrombosis, or myocardial infarction. Some of the dabigatran etexilate users had more than one of these thromboembolic events. One dabigatran etexilate user died.
Bleeding events, not all of which were major events, occurred in 22.5% of dabigatran etexilate users and 13.5% of warfarin users, FDA reported.
The study, according to ClinicalTrials.gov, was conducted in 48 locations in Europe and Canada.
Details of the study's design were described earlier this year in the American Heart Journal (PDF). Patients who were assigned to the dabigatran etexilate group would receive their initial doses of the drug of the basis of estimated creatinine clearance. Doses would then be adjusted on the basis of trough plasma dabigatran levels, with the goal of having steady-state levels of at least 50 ng/mL. No one would receive less than 150 mg twice a day or more than 300 mg twice a day.