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Michael D. Ezekowitz, MBChB, PhD; Jody A. Levine, BA

JAMA. 1999;281:1830-1835.

Context  Atrial fibrillation, a common disorder that affects nearly one sixth of the population aged 75 years and older, is a major risk factor for stroke.

Objectives  To review and evaluate the evidence supporting the use of warfarin and/or aspirin for stroke prevention in patients with atrial fibrillation.

Data Sources  Prospective, randomized trials of patients with atrial fibrillation evaluating either warfarin or aspirin or both, from MEDLINE from January 1, 1966, to February 23, 1999.

Study Selection  Five primary prevention placebo-controlled studies, which had been formally pooled, 1 study evaluating secondary prevention of stroke, 1 study comparing warfarin with aspirin, and 3 studies of warfarin in combination with aspirin were identified.

Data Synthesis  The risk of developing stroke is heterogeneous and increases with each decade above 65 years; history of high blood pressure, diabetes mellitus, previous transient ischemic attack, or stroke; poor ventricular function; and in women older than 75 years. For patients younger than 65 years, without risk factors, and not receiving antithrombotic therapy, the risk of stroke is 1%/y; those without risk factors between the ages of 65 and 75 years have a risk of 1.1%/y if taking warfarin and 1.4%/y if taking aspirin. For all other patients, stroke risk is reduced from an untreated rate of between 4.3%/y and more than 12%/y to a rate of 1.2%/y to 4%/y with warfarin use.

Conclusion  The protection afforded by warfarin is most pronounced in patients at the highest risk for stroke, while aspirin treatment seems adequate in low-risk populations.

Author Affiliations: Yale Clinical Trials Office, Yale University School of Medicine, New Haven, Conn (Dr Ezekowitz and Mr Levine), and the Veterans Affairs Medical Center, West Haven, Conn (Dr Ezekowitz).

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