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On October 19, 2010, dabigatran (Pradaxa; an oral thrombin inhibitor) was approved by the FDA to lower risk for thrombus and stroke in patients with atrial fibrillation. Unlike warfarin, dabigatran is given in fixed twice-daily doses and does not require international normalized ratio (INR) monitoring. The approval comes on the heels of the RE-LY trial, in which >18,000 people were randomized to one of two twice-daily doses of dabigatran (110 mg or 150 mg) or to dose-adjusted warfarin and were followed for a median of 2 years (JW Cardiol Sep 1 2009).
In RE-LY, risk for systemic embolism or stroke was 1.7% in the warfarin group, 1.5% in the 110-mg group, and significantly lower — 1.1% — in the 150-mg group. The rate of major bleeding was significantly lower in the 110-mg group (2.7% annually) than in the warfarin group (3.4%) or in the 150-mg group (3.1%). Dyspepsia was almost twice as common with dabigatran as with warfarin, and the rate of myocardial infarction (MI) was higher in both dabigatran groups (0.5% annually for warfarin vs. 0.7% in both dabigatran groups).
Comment
The FDA's action gives physicians an alternative to warfarin in patients with atrial fibrillation who are at excess risk for stroke. Interestingly, only the 75-mg and 150-mg capsules were approved for this indication. Dabigatran should not be used in patients with renal dysfunction, severe heart-valve disorders, liver disease, recent stroke, or other conditions that raise risk for hemorrhage; data for other indications, such as mechanical valves, are lacking. MI risk should be monitored closely. Dabigatran also should not be given to pregnant women or patients with clinically significant dyspepsia.
But who should be treated with dabigatran instead of warfarin? Some experts suggest that we have little reason to switch patients with stable INRs who are doing well on warfarin, especially because the yearly cost of dabigatran likely will be thousands of dollars, whereas generic warfarin now is available at some U.S. pharmacies for pennies a day. Of course, the costs of INR monitoring are also relevant, although these might be less important to patients than out-of-pocket drug costs. Only time will tell to what extent dabigatran displaces warfarin and to what extent other emerging alternatives to warfarin (e.g., oral factor Xa inhibitors, such as rivaroxaban) will compete with dabigatran. But, in the meantime, anticipate frank discussions with — and many questions from — patients about the pros and cons of this new drug.