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Sunday, February 10, 2013

Adding antiplatelets to dabigatran, warfarin elevates major bleeding risk

ACP Hospitalist


The risk of major bleeding is increased when antiplatelet drugs are added to either dabigatran or warfarin, a new subgroup analysis confirmed.
Researchers performed a post-hoc analysis of an earlier trial showing that a 150-mg dose of dabigatran was superior and a 110-mg dose was non-inferior to warfarin for preventing stroke and systemic embolism in atrial fibrillation patients. In the subgroup analysis, researchers compared the safety and efficacy of the 110-mg and 150-mg doses of dabigatran to warfarin in subgroups of patients with and without concomitant aspirin or clopidogrel treatment. Results were published online Dec. 27 by Circulation.
Nearly 7,000 of the original study's 18,113 patients received an antiplatelet at some point during the study. Eight hundred and twelve patients took both aspirin and clopidogrel, 5,789 took aspirin alone, and 351 took clopidogrel alone. A history of prior myocardial infarction or coronary artery disease, hypertension, paroxysmal atrial fibrillation, male sex and diabetes were more common among patients who took antiplatelets.
Use of concomitant antiplatelets was associated with a higher rate of major bleeding (4.4% vs. 2.6%), regardless of whether patients took warfarin or either dose of dabigatran (overall hazard ratio [HR], 2.01; 95% CI, 1.79 to 2.25). The absolute risk of bleeding was lowest with the 110-mg dose of dabigatran (3.9% per year), followed by the 150-mg dose of dabigatran (4.4% per year) and warfarin (4.8% per year) in those who also took antiplatelets (P=0.05 for 110-mg dabigatran vs. warfarin; P=0.38 for 150-mg dabigatran vs. warfarin).
Risk of major bleeding was higher among patients taking dual antiplatelets vs. those taking single antiplatelets (HR, 2.31 vs. 1.60; P<0.001 for trend in all treatment groups), with absolute risk lowest with 110-mg dabigatran. Similar trends were seen with major, minor and extracranial bleeding, but not intracerebral hemorrhage, which had a low event rate.
Tandem use of antiplatelets and anticoagulants is common, the authors noted, and this analysis suggests the relative risk of bleeding is similar for dabigatran and warfarin. The risk rose 50% with one antiplatelet and doubled with two, they noted. Because absolute (not relative) rates of bleeding seemed lower with 110 mg of dabigatran, however, this dose may be preferable "in patients in whom bleeding risk is of concern, such as those requiring dual antiplatelet therapy," the authors wrote. Editorialists wrote that the 110-mg dose of dabigatran might be a safer alternative in patients who require low-dose aspirin in particular. Regardless, treatment with both agents "needs to be highly personalized, taking into account the thrombotic and bleeding risk of each individual patient," the editorialists wrote.
Separately, the U.S. Food and Drug Administration warned in late Decemberthat patients with mechanical heart valves should not use dabigatran to prevent major stroke or blood clots. Researchers recently stopped a trial of mechanical heart valve patients in Europe because the patients taking dabigatran were more likely than those taking warfarin to experience strokes, heart attacks and blood clots that formed on the valves. They also had more bleeding after valve surgery. Physicians should transition all patients with mechanical heart values who take dabigatran to another medication, the alert said.

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