Risk of Bleeding With Single, Dual, or Triple Therapy With Warfarin, Aspirin, and Clopidogrel in Patients With Atrial Fibrillation

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Abstract
Many patients with atrial fibrillation (AF) require long-term oral anticoagulation with vitamin K antagonists.1 Patients with AF often have coexisting vascular disease, such as ischemic heart disease, and, thus, an indication for platelet inhibitor therapy. Because platelet inhibitor therapy in patients with AF provides less protection against thromboembolic events than does regular oral anticoagulation therapy,2,3 the physician may choose to combine aspirin or clopidogrel with a standard anticoagulant or even to use triple therapy with aspirin, clopidogrel, and an oral anticoagulant.1,4 The safety of this approach is poorly documented and represents a major therapeutic dilemma. No studies address dual therapy with an oral anticoagulant and clopidogrel, and studies addressing triple therapy are small and lack documentation for the duration of treatment. Consequently, estimates of risk vary significantly.5-11 Because undocumented combinations are endorsed in current international guidelines and expert statements for the treatment of AF,1,12 it is imperative that better estimates of safety are provided in terms of the risk of bleeding complications. Thus, in the present study, we examined a nationwide cohort of 118 606 patients with AF discharged from hospitals in Denmark between January 1, 1997, and December 31, 2006, to analyze the risk of hospitalization or death due to bleeding after treatment with warfarin, aspirin, clopidogrel, and combinations of these drugs.