Mavaddat N, Roalfe A, Fletcher K, Lip GYH, Hobbs FDR, Fitzmaurice D, and Mant J. Warfarin Versus Aspirin for Prevention of Cognitive Decline in Atrial Fibrillation: Randomized Controlled Trial (Birmingham Atrial Fibrillation Treatment of the Aged Study). Stroke. 2014
Atrial fibrillation (AF) is associated with impaired cognition. Knowing this association has led many to speculate that treatment with warfarin may reduce the accumulation of silent infarcts, thereby preventing or at least slowing cognitive decline. In this article, Mavvadat and colleagues analyzed the protective effects of warfarin by measuring cognitive function over time in warfarin vs. aspirin treated patients.
The authors performed a retrospective analysis using data from the Birmingham Atrial Fibrillation Treatment of the Elderly (BAFTA) study. 973 patients age > 75 with AF were randomized to aspirin (ASA) vs. warfarin if their primary care physician was undecided on the most appropriate treatment. Subjects received mini-mental status examinations (MMSE) at 9, 21, and 33 months after randomization. Of note, subjects were excluded from analysis if they suffered a symptomatic stroke. The authors found a non-significant effect favoring warfarin over ASA at 33 months (mean MMSE 26.9 vs. 26.4 respectively, P = 0.16) that was likely too small to be clinically meaningful.
This is the first study to test the ability of warfarin to prevent cognitive decline over time related to silent infarcts in patients with AF. Prior studies were confounded by inclusion of subjects with clinically symptomatic stroke during follow up. Unfortunately neuroimaging was not obtained in this study. It would be fascinating, for example, to determine whether there was a significant accumulation of silent infarcts on FLAIR despite little change in MMSE over time. This study suggests that undertreated AF has little impact on cognitive decline in the absence of new symptomatic infarcts. Despite these findings, the evidence for warfarin in terms of stroke prevention is overwhelming. Whenever possible we should push our primary care colleagues to choose warfarin (or one of the novel anticoagulant drugs) over aspirin for patients with AF.