Level 2: Mid-level evidence
Patients with atrial fibrillation (AF) who are unable to take warfarin for stroke prophylaxis frequently take aspirin instead. The Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events (ACTIVE A) evaluated the addition of clopidogrel to daily aspirin for stroke prophylaxis in 7,554 patients with AF (mean age 71 years) who were followed for median 3.6 years (N Engl J Med. 2009;360:2066-2078; available at content.nejm.org/cgi/content/full/360/20/2066, accessed June 11, 2009). 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 four years. The annual rate of stroke was reduced in the clopidogrel group compared with the placebo group (2.4% vs. 3.3%, P <.001, NNT 111), as was the annual rate of disabling or fatal stroke (1.6% vs. 2.1%, P =.001, NNT 200). The MI rate was marginally lower for clopidogrel (0.7% vs. 0.9%, P =.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 <.001, NNH 142), with significant differences in severe bleeding (1.5% vs. 1%, P <.001, NNH 200), major GI bleeding with transfusion (0.9% vs. 0.5%, P <.001, NNH 250), and intracranial bleeding (0.4% vs. 0.2%, P =.006, NNH 500). Fatal bleeding events were marginally higher for clopidogrel (0.3% vs. 0.2%, P =.07) than for placebo.