I read with interest the report regarding the combination of aspirin and clopidogrel versus aspirin alone for stroke prevention in those deemed unsuitable for warfarin therapy. As the investigators point out, there was modest stroke reduction (relative risk reduction 28%) in the Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events–Aspirin (ACTIVE-A) trial, but at the cost of increased bleeding. This study was the basis for their cost-effectiveness analysis. However, the Apixaban Versus Acetylsalicylic Acid to Prevent Strokes (AVERROES) investigators recently demonstrated much more impressive reductions in stroke (relative risk reduction >50%) with the oral factor Xa inhibitor apixaban, compared to aspirin, in patients with atrial fibrillation deemed unsuitable for warfarin therapy. In addition, this benefit was seen without a corresponding increase in major bleeding or intracranial hemorrhage. The 2 studies were large (7,554 and 5,599 subjects, respectively) and both reported similar refusal of warfarin therapy. The subsequent publication of the Apixaban Versus Warfarin in Patients With Atrial Fibrillation (ARISTOTLE) trial has shown apixaban to be noninferior to warfarin in stroke reduction but with less bleeding. The definition of warfarin unsuitability, however, is not clear in the randomized trials or in everyday practice. This is relevant given the recent shift in favor of “oral anticoagulants” for stroke risk reduction in patients with atrial fibrillation rather than aspirin, given that it is relatively ineffective. This is highlighted in the recent European guidelines for the management of atrial fibrillation.
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