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(Stroke. 2004;35:1519.)
© 2004 American Heart Association, Inc.

Emerging Therapies

Direct Thrombin Inhibition

A Novel Approach to Stroke Prevention in Patients With Atrial Fibrillation

From the Department of Neurology (M.S.E., R.L.S.), College of Physicians and Surgeons, Columbia University, and the Columbia University Medical Center of New York–Presbyterian Hospital, New York; the Sergievsky Center (M.S.E., R.L.S.), College of Physicians and Surgeons, Columbia University, New York; and the Division of Epidemiology (R.L.S.), Joseph P. Mailman School of Public Health, Columbia University, New York.

Correspondence to Dr Mitchell S. Elkind, Neurological Institute, 710 W 168th St, New York, NY 10032. E-mail mse13@columbia.edu

Key Words: atrial fibrillation • cerebral embolism • direct thrombin inhibitor • stroke prevention • ximelagatran

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Atrial fibrillation (AF) is the most common cause of cardioembolic ischemic stroke, particularly in the elderly, in whom it accounts for as many as 24% of strokes.¹ As the population ages, it is anticipated that the number of strokes caused by AF will increase. Anticoagulant therapy with coumarin derivatives (primarily warfarin) is considered the optimal strategy to reduce the risk of stroke in patients with AF. Warfarin inhibits the vitamin K-dependent post-translational modification of certain coagulation factors (factors II, VII, IX, and X, as well as the anticoagulant factors protein C and protein S) in the liver. This leads to a reduction in generation of thrombin, which is the final rate-limiting step in the coagulation cascade. Thrombin, a serine protease, cleaves fibrinopeptides from soluble fibrinogen to form insoluble fibrin, leading to thrombus formation.

Most trials of anticoagulant therapy in AF have tested the role of warfarin in primary prevention, with relative risk reductions for stroke ranging from 56% to 86% compared with placebo and a pooled risk reduction of 68% (95% confidence interval [CI] 50% to 79%).^2–5 Warfarin is superior to aspirin, particularly in higher-risk patients with AF. A recent meta-analysis⁶ using individual patient data found that warfarin significantly reduced the risk of the combination of hemorrhagic and ischemic strokes compared with aspirin (hazard ratio of warfarin 0.55, 95% CI 0.43 to 0.71). The benefit was seen in all patient groups, but the absolute risk reductions were greatest in those at highest risk, including those over age 75. Aspirin may . . . [Full Text of this Article]