The ACTIVE Investigators. Effect of clopidogrel added to aspirin in patients with atrial fibrillation. N. Engl. J. Med. doi:10.1056/NEJMoa0901301 (2009).

The addition of clopidogrel to aspirin reduces the risk of vascular events, particularly stroke, in patients with atrial fibrillation (AF), according to a report by the ACTIVE investigators.

Vitamin K antagonists, such as warfarin, are currently recommended for individuals with AF who have additional risk factors for stroke. However, these drugs are not suitable for all patients—they are associated with a high risk of hemorrhage, can interact adversely with other medications, and require the patient to be regularly monitored. Establishing a safe and effective medical regimen for the prevention of stroke in patients with AF who have contraindications to warfarin therapy is, therefore, important.

“prevention of stroke in patients with AF who have contraindications to warfarin therapy is ... important”

ACTIVE A was an international, randomized, double-blind, placebo-controlled trial. Enrolled patients had AF with at least one other risk factor for stroke, and were not considered to be candidates for vitamin K antagonist therapy. All enrolled patients received aspirin (75–100 mg daily) and the investigators randomly assigned patients to also receive placebo (n = 3,782) or 75 mg per day of clopidogrel (n = 3,772) daily.

Participants in this study were elderly (mean age 71 years); at baseline 82.7% of patients were already taking aspirin and 23.0% were receiving an antiarrhythmic medication. The researchers found that clopidogrel was associated with an 11% reduction in the incidence of major vascular events, which was principally the result of a 28% reduction in stroke, when compared with placebo. However, the incidence of major hemorrhage was higher in the clopidogrel group than in the placebo group. There were 1,666 deaths during the study, 9.8% of which were caused by stroke, but there were no significant differences in the rates of all-cause or vascular mortality between the two treatment groups.

Guidelines for the treatment of patients with AF call for individualized anticoagulation strategies on the basis of the patient's risk profile. The results of ACTIVE A could help physicians determine which anticoagulant regimen is best for their patient.