Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation - Analysis of 2012 participants in the SPAF I-III clinical trials

Background and Purpose-Nonvalvular atrial fibrillation (AF) is a strong, in dependent risk factor for stroke, but the absolute rate of stroke varies wi dely among AF patients, importantly influencing the potential benefit of an tithrombotic prophylaxis. We explore factors associated with ischemic strok e in AF patients taking aspirin. Methods-We performed multivariate logistic regression analysis of 2012 part icipants given aspirin alone or in combination with low, inefficacious dose s of warfarin in the Stroke Prevention in Atrial Fibrillation I-III trials followed for a mean of 2.0 years, during which 130 ischemic strokes were ob served. Results-Age (relative risk [RR]=1.8 per decade, P<0.001), female sex (RR=1. 6, P=0.01), history of hypertension (RR=2.0, P<0.001), systolic blood press ure >160 mm Hg (RR=2.3, P<0.001), and prior stroke or transient ischemic at tack (RR=2.9, P<0.001) were independently associated with increased stroke risk. Regular consumption of greater than or equal to 14 alcohol-containing drinks per week was associated with reduced stroke risk (adjusted RR=0.4, P=0.04). Among SPAF III participants, estrogen hormone replacement therapy was associated with a higher risk of ischemic stroke (adjusted RR=3.2, P=0. 007). With the use of these variables, a risk stratification scheme for pri mary prevention separated participants into those with high (7.1%/y, 22% of the cohort), moderate (2.6%/y, 37% of the cohort), and low (0.9%/y, 41% of the cohort) rates of stroke. Ischemic strokes in low-risk participants wer e less often disabling (P<0.001). Conclusions-Patients with AF who have high and low rates of stroke during t reatment with aspirin can be identified. However, validation of our risk st ratification scheme is necessary before it can be applied with confidence t o clinical management. Postmenopausal. estrogen replacement therapy and mod erate alcohol consumption may additionally modify the risk of stroke in AF, but these findings require confirmation.