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Lessons from the Stroke Prevention in Atrial Fibrillation Trials

Robert G. Hart, MD; Jonathan L. Halperin, MD; Lesly A. Pearce, MS; David C. Anderson, MD; Richard A. Kronmal, PhD; Ruth McBride, BS; Elaine Nasco, BA; David G. Sherman, MD; Robert L. Talbert, PharmD; John R. Marler, MD, Stroke Prevention in Atrial Fibrillation Investigators*
[+] Article and Author Information

From University of Texas Health Science Center, San Antonio, Texas; The Zena and Michael A. Weiner Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York; Hennepin County Medical Center, University of Minnesota Medical School, Minneapolis, Minnesota; University of Washington and Axio Research Corporation, Seattle, Washington; University of Texas School of Pharmacy, Austin, Texas; and National Institute of Neurological Disorders and Stroke, Bethesda, Maryland.


Grant Support: By grant RO1 NS 24-224 from the National Institute of Neurological Disorders and Stroke, National Institutes of Health.

Potential Financial Conflicts of Interest:Consultancies: J.L. Halperin (AstraZeneca); Honoraria: J.L. Halperin (AstraZeneca); Grants received: J.L. Halperin (AstraZeneca).

Requests for Single Reprints: Robert G. Hart, MD, Department of Medicine (Neurology), University of Texas Health Science Center, 7703 Floyd Curl Drive MC 7883, San Antonio, TX 78229-3900; e-mail, hartr@uthscsa.edu.

Current Author Addresses: Drs. Hart and Sherman: Department of Medicine (Neurology), University of Texas Health Science Center, 7703 Floyd Curl Drive MC 7883, San Antonio, TX 78229-3900.

Dr. Halperin: The Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai Medical Center, Box 1030, Fifth Avenue at 100th Street, New York, NY 10029-6574.

Ms. Pearce: 2509 Bel Air Court, Minot, ND 58703.

Dr. Anderson: Department of Neurology, Hennepin County Medical Center, 701 Park Avenue South, Minneapolis, MN 55415.

Dr. Kronmal: Department of Biostatistics, University of Washington, 600 Stewart Street, Suite 700, Seattle, WA 98195.

Ms. McBride and Ms. Nasco: Axio Research Corporation, 2601 Fourth Avenue, Suite 200, Seattle, WA 98121.

Dr. Talbert: Department of Pharmacotherapy, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900.

Dr. Marler: National Institute of Neurological Disorders and Stroke, Neuroscience Center, Suite 2216, 6001 Executive Boulevard, Rockville, MD 20892-9520.


Ann Intern Med. 2003;138(10):831-838. doi:10.7326/0003-4819-138-10-200305200-00011
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Atrial fibrillation predisposes to left atrial thrombus formation and carries a sixfold increased risk for stroke. Antithrombotic therapies are the mainstay for stroke prevention. The National Institute of Neurological Disorders and Strokesponsored Stroke Prevention in Atrial Fibrillation (SPAF) studies assessed the value of warfarin, aspirin, and their combination for preventing stroke in six multicenter trials involving 3950 participants. This review presents the major results and implications, which offer unique perspectives on antithrombotic therapies for stroke prevention in atrial fibrillation.

Warfarin and aspirin reduce stroke. Anticoagulation substantially benefits high-risk patients with atrial fibrillation, while many younger patients with atrial fibrillation have a low stroke rate when given aspirin. Pathogenetic and transesophageal echocardiographic correlations shed light on mechanisms by which antithrombotic agents prevent stroke. Warfarin inhibits formation of atrial appendage thrombi and markedly reduces cardioembolic strokes, while aspirin primarily prevents smaller, noncardioembolic strokes. The SPAF III stroke risk stratification scheme has been validated for identifying patients with high versus moderate versus low risk for stroke. Women with atrial fibrillation benefit from anticoagulation significantly more than men do. Many elderly patients with recurrent paroxysmal atrial fibrillation have high rates of stroke.

Antithrombotic prophylaxis should be individualized on the basis of the estimated risk for stroke during aspirin therapy and the risk for bleeding during anticoagulation. Overall, nearly one third of patients with atrial fibrillation are low risk and should be treated with aspirin, and about one third are high risk and should receive warfarin if it can be given safely. For patients at moderate risk for stroke, patient preferences and access to reliable anticoagulation monitoring are particularly relevant.

For members of the Stroke Prevention in Atrial Fibrillation Investigators, see the Appendix.

Figures

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Figure 1.
Design of the Stroke Prevention in Atrial Fibrillation (SPAF) trials.

INR = international normalized ratio; LV = left ventricular.

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Figure 2.
Combined rates of ischemic and hemorrhagic strokes according to antithrombotic therapy assignment in Stroke Prevention in Atrial Fibrillation I (top), II (middle), and III (bottom) trials.

Error bars represent upper bound of 95% CI. HTN = hypertension; INR = international normalized ratio.

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