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.

1.
Miller VT, Rothrock JF, Pearce LA, Feinberg WM, Hart RG, Anderson DC: Ischemic stroke in patients with atrial fibrillation: Effect of aspirin according to stroke mechanism. Neurology 1993;43:32–36.
2.
Bogousslavsky J, van Melle G, Regli F, Kappenberger L: Pathogenesis of anterior circulation stroke in patients with nonvalvular atrial fibrillation. Neurology 1990;40:1046–1050.
3.
Miller VT, Pearce LA, Feinberg WM, Rothrock JF, Anderson DC, Hart RG: Differential effect of aspirin vs. warfarin on clinical stroke types in patients with atrial fibrillation. Neurology 1996;46:238–240.
4.
Stroke Prevention in Atrial Fibrillation Investigators: The Stroke Prevention in Atrial Fibrillation III Study: Rationale, design and patient features. J Stroke Cerebrovasc Dis 1997;6:341–353.
5.
Stroke Prevention in Atrial Fibrillation Investigators: Adjusted-dose warfarin versus low-intensity, fixed-dose warfarin plus aspirin for high-risk patients with atrial fibrillation: Stroke Prevention in Atrial Fibrillation III randomised clinical trial. Lancet 1996;348:633–638.
6.
Stroke Prevention in Atrial Fibrillation Study Investigators: Patients with nonvalvular atrial fibrillation at low risk of stroke during treatment with aspirin: Stroke Prevention in Atrial Fibrillation III Study. JAMA 1998;279:1273–1277.
7.
Stroke Prevention in Atrial Fibrillation Investigators: Warfarin versus aspirin for the prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet 1994;343:687–691.
8.
Stroke Prevention in Atrial Fibrillation Investigators: Stroke Prevention in Atrial Fibrillation Study: Final results. Circulation 1991;84:527–539.
9.
Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B: Placebo-controlled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: The Copenhagen AFASAK Study. Lancet 1989;i:175–179.
10.
Hart RG, Benavente O, McBride R, Pearce LA: Antithrombotic therapy to prevent stroke in atrial fibrillation: Meta-analysis of 15 randomized trials. Submitted.
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