Is Pradaxa (dabigatran etexilate) better at reducing the risk for stroke than Coumadin (warfarin) in patients with atrial fibrillation?
For many years, Coumadin has been the oral anticoagulant of choice as prophylaxis against thrombus formation in conditions like atrial fibrillation; however, drug interactions with antibiotics, psychiatric drugs, and other drug classes have made dosing and monitoring the extent of warfarin-based anticoagulation troublesome. Pradaxa, a direct thrombin inhibitor, is the first oral anticoagulant approved by the US Food and Drug Administration in over fifty years. This new drug eliminates the need for conventional “INR monitoring” and is associated with significantly fewer drug interactions and dietary restrictions compared to Coumadin.
In the RE-LY® trial, over 18,000 patients from 44 countries (all with a history of A-fib on EKG at screening or within six months before entering the trial) were assigned into three groups: 110 mg Pradaxa b.i.d, 150 mg Pradaxa b.i.d, and warfarin (adjusted for therapeutic INR between 2.0 and 3.0). The primary outcome was a systemic embolism or stroke. Follow-ups were done, on average, two years later.
|Coumadin||Pradaxa 110 mg||Pradaxa 150 mg|
The results of this trial were strongly in Pradaxa’s favor. There were a reduction in the incidence of systemic emboli, stroke, major bleeding, and overall mortality in patients taking Pradaxa relative to those on Coumadin. The higher dose of Pradaxa (150 mg) was associated with a similar risk of major hemorrhage compared to Coumadin.1
In spite of the success, a larger percentage of participants on Pradaxa discontinued their enrollment in the trial because of gastrointestinal symptoms like pain, vomiting, and diarrhea. Pradaxa is better absorbed at a low pH, so the tablets contain a tartaric acid core which may have caused the GI irritation.
Additional research is required to assess the long-term efficacy and safety for Pradaxa in other conditions where anticoagulation is indicated, but initial studies look promising in atrial fibrillation patients for prophylaxis against thrombotic events like strokes. With the United States’ healthcare system in a hotbed of fluctuation, the cost effectiveness of Pradaxa may be something to assess in more depth. Does the cost of warfarin (and necessary INR monitoring tests) make it more suitable for clinical use, or does the additional safety of Pradaxa justify its costs? This question and others will need to be further investigated as physicians learn more about the efficacy of Pradaxa in clinical practice.
1. “Dabigatran versus Warfarin in Patients with Atrial Fibrillation” http://www.nejm.org/doi/full/10.1056/NEJMoa0905561