Aspirin for Atrial Fibrillation

CLINICAL QUESTION: In a low-risk primary care population, is warfarin more effective than aspirin in preventing thromboembolism?

BACKGROUND: Studies of patients with atrial fibrillation have shown that warfarin is more effective than aspirin in reducing the risk of thromboembolism. It is unclear whether this finding is generalizable to primary care settings, since patients in these particular studies may be at higher risk than the typical family practice patient. The purpose of this study was to compare the rates of thromboembolism and the side effects of aspirin and warfarin in low-risk primary care patients with atrial fibrillation.

POPULATION STUDIED: A total of 729 patients aged 60 years and older were recruited from 284 general practices in the Netherlands. The pulse of all older patients visiting these practices was taken to identify those with atrial fibrillation for this study. Atrial fibrillation was confirmed by electrocardiogram. Patients were excluded if they had rheumatic valvular disease; previous stroke or systemic embolism; treatable causes of atrial fibrillation; contraindications to anticoagulation; or a history of recent warfarin use, myocardial surgery, or infarction.

STUDY DESIGN AND VALIDITY: This was a randomized single-blind controlled trial. Patients eligible for standard intensity warfarin were randomly assigned to either regular-dose warfarin (to achieve an international normalized ratio [INR] of 2.5 - 3.5), low-intensity warfarin (INR = 1.1 - 1.6), or aspirin 150 mg per day (stratum 1). Patients ineligible for standard-dose anticoagulation were randomly assigned to low-dose warfarin or aspirin (stratum 2). Patients were unaware of their intensity of anticoagulant. However, they were not blinded as to which medication (aspirin or warfarin) they were taking. Evaluators were unaware of treatment. This study enrolled patients at low baseline risk of embolism. Twenty-eight percent of the patients were taking aspirin before entering the trial. Although aspirin use was stopped before randomization, this group may have been at lower risk for thromboembolism. It is likely that this study had a predominantly white population. The results may not be generalizable to blacks, who have a higher rate of strokes than whites for any given level of blood pressure. Sample size calculations showed that the study had sufficient statistical power to compare low-intensity anticoagulation (INR = 1.1 - 1.6)—but not standard anticoagulation—to aspirin. The low rate of events in the group as a whole (5.5% per year) made it difficult to find differences in outcome between the treatment groups. In addition, the study was too small to detect a difference in outcome between the standard anticoagulation and aspirin groups.

OUTCOMES MEASURED: The primary outcomes were stroke, systemic embolism, major hemorrhage, and vascular death. Secondary outcomes were nonfatal myocardial infarction, retinal infarction, transient ischemic attack, minor bleeding, and nonvascular death. results n During an average follow-up period of 2.7 years, 108 patients (5.5% per year) suffered a major event. This rate of stroke and other events is lower than in the typical populations studied in the past. There was no difference in the incidence of these major events in patients receiving aspirin or low or standard anticoagulation. Nonvascular death was less common in the low-anticoagulation group than in the aspirin group (hazard ratio = 0.41; 95% confidence interval, 0.20 - 0.82). Major bleeding events occurred in 0.7% of patients per year; this rate was not different among the 3 groups.