In October 2010, FDA approved dabigatran etexilate (Pradaxa, Boehringer Ingelheim), the first oral direct thrombin inhibitor for the prevention of thromboembolic stroke in patients with nonvalvular atrial fibrillation.
Dabigatran has poor bioavailability and reaches peak levels in approximately 0.5 hours to 2 hours after administration. Its half-life is 15 hours to 17 hours, though this may be increased in patients with renal dysfunction.
Approval in the United States was based on data from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial, a study of approximately 18,000 patients.
The results showed that dabigatran 150 mg bid reduced the annualized risk of stroke and systemic embolism by 34% compared to warfarin. This 150-mg dose also reduced the risk of hemorrhagic stroke by 74% compared with warfarin.
The higher dabigatran dose was associated with a slightly but significantly (P=.048) increased risk of myocardial infarction, a secondary end point.
Bleeding risks were similar for warfarin and dabigatran 150 mg bid. The percentage of patients with bleeding events was 2.2% for dabigatran etexilate 150 mg bid (n=134), 3% (n=182) for dabigatran etexilate 110 mg bid, and 3.4% for warfarin (n=202).
The 110-mg dose of dabigatran was not shown to be significantly more effective than warfarin.
On the basis of these data, FDA approved the 150-mg dose. The agency also approved a 75-mg dose for patients with renal dysfunction (CrCl 15-30 mL/min). This dose has not been studied and was determined using the pharmacokinetic profile of the drug.
Advantages of new treatment
Treatment with dabigatran requires no monitoring or related dose adjustments. It is unaffected by food, and it has shown few drug interactions to date. These results are all major advances in anticoagulation treatment.
Other advantages include:
Potential treatment pitfalls
Despite the advantages that dabigatran clearly presents, several considerations may make it less appealing for use by some patient populations. These include: