For patients with atrial fibrillation unable to take warfarin for stroke prophylaxis, aspirin is frequently used instead. The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE A) trial evaluated the addition of clopidogrel to daily aspirin for stroke prophylaxis in 7,554 patients with atrial fibrillation (mean age 71 years) who were followed for median 3.6 years.  All patients had elevated risk of stroke but were unsuited for vitamin K-antagonist therapy by physician’s judgment, personal preference, or prior risk of bleeding.  Treatment had been discontinued in 39% of the clopidogrel group and 31% of the placebo group at 4 years.  The annual rate of stroke was reduced in the clopidogrel group (2.4% vs. 3.3%, p < 0.001, NNT 111) as was the annual rate of disabling or fatal stroke (1.6% vs. 2.1%, p = 0.001, NNT 200) (level 2 [mid-level] evidence).  The myocardial infarction rate was marginally lower for clopidogrel (0.7% vs. 0.9%, p = 0.08), but there were no significant differences in annual all-cause mortality (6.4% vs. 6.6%), or vascular mortality (4.7% vs. 4.7%).  The annual rate of major bleeding events was higher in the clopidogrel group (2% vs. 1.3%, p < 0.001, NNH 142), with significant differences in severe bleeding (1.5% vs. 1%, p < 0.001, NNH 200), major gastrointestinal bleeding with transfusion (0.9% vs. 0.5%, p < 0.001, NNH 250) and intracranial bleeding (0.4% vs. 0.2%, p = 0.006, NNH 500).  Fatal bleeding events were marginally higher for clopidogrel (0.3% vs. 0.2%, p = 0.07) (N Engl J Med 2009 May 14;360(20):2066).  For more information, see the Thromboembolic prophylaxis in atrial fibrillation topic in DynaMed.