Cardioembolic vs. Noncardioembolic Strokes in Atrial Fibrillation: Frequency and Effect of Antithrombotic Agents in the Stroke Prevention in Atrial Fibrillation Studies

Background: While atrial fibrillation (AF) increases the risk of cardioembolic stroke, some ischemic strokes in AF patients are noncardioembolic. Objectives: To assess ischemic stroke mechanisms in AF and to compare their responses to antithrombotic therapies. Methods: On-therapy analyses of ischemic strokes occurring in 3,950 participants in the Stroke Prevention in Atrial Fibrillation I–III clinical trials. Strokes were classified by presumed mechanism according to specified neurologic features by neurologists unaware of antithrombotic therapy. Results: Of 217 ischemic strokes, 52% were classified as probably cardioembolic, 24% as noncardioembolic, and 24% as of uncertain cause (i.e., 68% of classifiable infarcts were deemed cardioembolic). Compared to those receiving placebo or no antithrombotic therapy, the proportion of cardioembolic stroke was lower in patients taking adjusted-dose warfarin (p = 0.02), while the proportion of noncardioembolic stroke was lower in those taking aspirin (p = 0.06). Most (56%) ischemic strokes occurring in AF patients taking adjusted-dose warfarin were noncardioembolic vs. 16% of strokes in those taking aspirin. Adjusted-dose warfarin reduced cardioembolic strokes by 83% (p < 0.001) relative to aspirin. Cardioembolic strokes were particularly disabling (p = 0.05). Conclusions: Most ischemic strokes in AF patients are probably cardioembolic, and these are sharply reduced by adjusted-dose warfarin. Aspirin in AF patients appears to primarily reduce noncardioembolic strokes. AF patients at highest risk for stroke have the highest rates of cardioembolic stroke and have the greatest reduction in stroke by warfarin.