Effect of ximelagatran and warfarin on stroke subtypes in atrial fibrillation.
OBJECTIVE
The most common stroke subtype among atrial fibrillation (AF) patients not receiving anticoagulants is cardioembolic. In the SPORTIF III and V trials, the oral direct thrombin inhibitor ximelagatran was as effective as warfarin in reducing the risk of stroke in patients with nonvalvular AF. We assessed any differential effect of warfarin versus ximelagatran on the risk and outcome of cardioembolic and noncardioembolic stroke.


METHODS
7329 patients with AF and > or = 1 risk factors for stroke were randomized to treatment with warfarin (target international normalized ratio 2.0--3.0) or fixed-dose ximelagatran. Strokes were classified into specific subtypes. Therapeutic effect of warfarin and ximelagatran, adverse events, and stroke outcomes were assessed according to stroke subtype.


RESULTS
The annual stroke rate was low for both cardioembolic (ximelagatran, 0.39%; warfarin, 0.47%) and noncardioembolic stroke (ximelagatran, 0.57%; warfarin, 0.37%). In ischemic strokes, 33.9% (ximelagatran) and 34.3% (warfarin) had strokes of presumed cardioembolic origin. When fatal stroke, disabling stroke, myocardial infarction, and death from any cause were combined as poor outcome, patients with cardioembolic strokes had the highest rate of poor outcome (40%) but this was non- significant.


CONCLUSIONS
In SPORTIF III and V the efficacy of warfarin and ximelagatran were similar for prevention of cardioembolic and noncardioembolic strokes. Overall outcome tended to be worse following cardioembolic stroke. Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied.
Department of Neurology, Montreal Neurological Institute and Hospital, Montreal, Quebec, Canada.
Jeanne S
JS
Teitelbaum
Rüdiger
R
von Kummer
Knut
K
Gjesdal
Arni
A
Kristinsson
Georg
G
Gahn
Gregory W
GW
Albers
D000925:Anticoagulants / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications* / Q000517:prevention & control; D001384:Azetidines / Q000627:therapeutic use*; D001596:Benzylamines / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D020521:Stroke / Q000145:classification / Q000209:etiology* / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use*
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C426686:ximelagatran; D014859:Warfarin