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David Plaut: Off the Cuff

Warfarin and Dabigatran

Published September 28, 2009 12:52 PM by David Plaut

Coumadin (Warfarin) has long been used to treat patients with atrial fibrillation. There is no doubt that Coumadin reduces the risk of stroke in the patients. However, the risk of hemorrhage and systemic embolism is increased. In addition to the risk factors associated with the drug, it is difficult to use for some patients. It requires periodic measurement of prothromin time (PT, INR), which can be weekly for some. Effective use of the drug also requires diet restrictions—especially green vegatables.

For some years, there has been a search of a different type of drug that would reduce the risks and be easier to use. In August (www.nejm.org August 30, 2009 ) the RE-LY group reported a large study patients with atrial fibrillation. The group reported that “dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin, as well as lower rates of major hemorrhage. Dabigatran administered at a dose of 150 mg, as compared with warfarin, was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage. The benefit of dabigatran may be explained in part by the twice-daily dosing regimen. Since dabigatran has an elimination half-life of 12 to 17 hours, twice-daily dosing reduces variability in the anticoagulation effect, especially as compared with the anticoagulation effect of warfarin, which is difficult to control. Warfarin broadly inhibits coagulation. By selectively inhibiting only thrombin, dabigatran may have antithrombotic efficacy while preserving some other hemostatic mechanisms in the coagulation system and thus potentially mitigating the risk of bleeding.

An editorial in the same issue noted that “Because of dabigatran's twice-daily dosing and greater risk of nonhemorrhagic side effects, patients already taking warfarin with excellent INR control have little to gain by switching to dabigatran. In contrast, many other patients who have atrial fibrillation and at least one additional risk factor for stroke could benefit from dabigatran.”

posted by David Plaut

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