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Effect of Ximelagatran and Warfarin on Stroke Subtypes in Atrial Fibrillation

  • Jeanne S. Teitelbaum, Rüdiger von Kummer, Knut Gjesdal, Arni Kristinsson, Georg Gahn and Gregory W. Albers...

Abstract

Background and Purpose:

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 ≥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 Ximelagatran has been withdrawn from the market due to hepatic side effects, but similar compounds are presently being studied.

<span class='bold'>RÉSUMÉ:</span> <span class='bold'> <span class='italic'>Contexte et Objectif:</span> </span>

Le sous–type le plus frequent d’accident vasculaire cerebral (AVC), chez les patients porteurs de fibrillation auriculaire (FA) qui ne sont pas anticoagules, est l’AVC d’origine cardioembolique. Dans les essais cliniques SPORTIF III et V, un inhibiteur direct de la thrombine, le ximelagatran, administre par voie orale, etait aussi efficace que la warfarine pour diminuer le risque d’AVC chez les patients atteints de FA non valvulaire. Nous avons evalue l’effet de ces deux agents sur le risque et l’issue d’un AVC cardioembolique et non cardioembolique.

<span class='bold'> <span class='italic'>Méthodes:</span> </span>

Septmille trois cent vingt–neuf patients atteints de FA, porteurs d’un facteur de risque d’AVC ou plus, ont ete randomises a l’un des deux traitements suivants : la warfarine (INR cible de 2,0 à 3,0) ou une dose fixe de ximelagatran. Les AVC etaient classifies en sous–types specifiques. L’effet therapeutique de la warfarine et du ximelagatran, les effets indesirables et l’issue des AVC etaient evalues selon le sous–type d’AVC.

<span class='bold'> <span class='italic'>Résultats:</span> </span>

Le taux annuel d’AVC tant cardioembolique (ximelagatran 0,39%; warfarine 0,47%) que non cardioembolique (ximelagatran 0,57%; warfarine 0,37%) etait faible. Parmi les AVC ischemiques, 33,9% (ximelagatran) et 34,3% (warfarine) des AVC ont ete presumes d’origine cardioembolique. En combinant l’AVC fatal, l’AVC invalidant, l’infarctus du myocarde et le deces de toutes causes comme issues defavorables, les patients qui avaient subi un AVC cardioembolique avaient le taux le plus eleve d’issues defavorables (40%), ce qui n’atteignait cependant pas le seuil de la signification statistique.

<span class='bold'> <span class='italic'>Conclusions:</span> </span>

L’efficacite de la warfarine et du ximelagatran etaient similaires au cours des essais cliniques SPORTIF III et V pour prevenir les AVC d’origine cardioembolique et non cadioembolique. L’issue avait tendance a etre moins bonne apres un AVC cardioembolique. Le ximelagatran a ete retire du marche a cause d’effets secondaires hepatiques. Cependant on etudie presentement des composes similaires.

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References

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Effect of Ximelagatran and Warfarin on Stroke Subtypes in Atrial Fibrillation

  • Jeanne S. Teitelbaum, Rüdiger von Kummer, Knut Gjesdal, Arni Kristinsson, Georg Gahn and Gregory W. Albers...

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