Warfarin Versus Aspirin for Prevention of Cognitive Decline in Atrial Fibrillation

BACKGROUND AND PURPOSE: Atrial fibrillation is associated with decline of cognitive function. Observational evidence suggests that anticoagulation might protect against this decline. We report the first randomized controlled trial evidence on the effect of anticoagulation on cognitive function in elderly patients with atrial fibrillation. METHODS: A total of 973 patients aged≥75 years with atrial fibrillation were recruited from primary care and randomly assigned to warfarin (n=488; target international normalized ratio, 2-3) or aspirin (n=485; 75 mg/d). Neither participants nor investigators were masked to group assignment. Follow-up was for a mean of 2.7 years (SD, 1.2). Cognitive outcome was assessed using the Mini-Mental State Examination at 9-, 21-, and 33-month follow-up. Participants who had a stroke were censored from the analysis, which was by intention to treat with imputation for missing data. RESULTS: There was no difference between mean Mini-Mental State Examination scores in people assigned to warfarin or aspirin at 9 or 21 months. At 33-month follow-up, there was a nonsignificant difference of 0.56 in favor of warfarin that decreased to 0.49 (95% confidence interval, -0.01 to 0.98) after imputation. CONCLUSIONS: We found no evidence that anticoagulation confers clinically important protection over aspirin against cognitive decline as measured by the Mini-Mental State Examination in atrial fibrillation in the first 33 months of treatment other than that provided by preventing clinical stroke. CLINICAL TRIAL REGISTRATION URL: http://www.controlled-trials.com. Unique identifier: ISRCTN89345269.