Ximelagatran^[*] zur Therapie und Sekundärprophylaxe der tiefen Venenthrombose

Zusammenfassung

Die Therapie und Rezidivprophylaxe der venösen Thromboembolie mit Heparin/niedermolekularem Heparin und Vitamin- K-Antagonisten wird durch eine Anzahl von Faktoren beeinträchtigt. Orale direkte Thrombininhibitoren (ODTI) weisen ein verbessertes pharmakologisches Prinzip auf und könnten eine Alternative in der Therapie der venösen Thromboembolie darstellen. Das THRIVE(Thrombin Inhibition in Venous thromboembolism)-Programm entwickelte mit mehreren Studien den ODTI Ximelagatran in dieser Indikation, das in der Übersicht dargestellt ist. Die Dosisfindung wurde in der THRIVE-I- und die Anwendbarkeit bei der hämodynamisch stabilen Lungenembolie in der THRIVE-IV-Studie untersucht. Eine randomisierte doppelblinde Studie prüfte Ximelagatran zur Therapie der proximalen Venenthrombose über 6 Monate im Vergleich zu Enoxaparin/Warfarin (THRIVE treatment). Die doppelblinde THRIVE-III-Studie verglich Ximelagatran mit Plazebo über 18 Monate nach initialer 6-monatiger konventioneller Antikoagulation der Beinvenenthrombose (BVT). 2 × 36 mg Ximelagatran ist der konventionellen 6-monatigen Rezidivprophylaxe der frischen BVT in Wirksamkeit und Verträglichkeit nicht unterlegen. 2 × 24 mg Ximelagatran reduziert über weitere 18 Monate die Thromboembolierezidive im Vergleich zu Plazebo ohne Zunahme von Blutungskomplikationen. Ein symptomloser, reversibler Anstieg der Alaninaminotransferase tritt bei etwa 6% bis 9,6% der Patienten nach 2 bis 4 Monaten auf.

Summary

The treatment of acute venous thromboembolism and prophylaxis of recurrent events with heparin/low molecular weight heparin followed by vitamin-K antagonists is limited by a number of factors. Oral direct thrombin inhibitors (ODTI) showed a better pharmacological activity and might be an alternative in the treatment of venous thromboembolism. The THRIVE (Thrombin Inhibition in Venous Thromboembolism) program performed some studies developing the ODTI ximelagatran for this indication, it is presented in the overview. The aim of the THRIVE I study was the dose finding, that of the THRIVE IV study the applicability in the haemodynamic stabile pulmonary embolism. A prospective, randomized, double-blind trial was performed to compare oral ximelagatran with enoxaparin/warfarin for a 6-months treatment of acute venous thrombosis (THRIVE treatment). Another double blind study compared ximelagatran with placebo over 18 months after a 6-months anticoagulant therapy of acute deep vein thrombosis. The efficacy and safety of treatment of patients with acute deep venous thrombosis with 2 × 36 mg ximelagatran is not inferior to a conventional anticoagulant for prophylaxis of recurrent events over 6-months. 2 × 24 mg ximelagatran significantly reduce recurrent thromboembolic events compared to placebo without increasing the risk for haemorrhage. A reversible symptomless increase of alanineaminotransferase occurs in 6% to 9,6% of patients between months 2 and 4.

Résumé

Le traitement du thromboembolism veineuse et la prophylaxie recidive avec de l‘héparine/l‘héparine á bas poids moléculaire et des antagonistes de vitamine-K est limité par un certain nombre de facteurs. Les inhibiteurs directs oraux de thrombine (ODTI) ont montré une meilleure activité pharmacologique et pourraient être une alternative dans le traitement du thromboembolism veineux. L‘inhibition de thrombine dans le programme veineux de Thromboembolism (THRIVE) a réalisé quelques études développant l‘ODTI Ximelagatran pour cette indication, il est présentée dans la vue d‘ensemble. Le but de la THRIVE I étude était la dose trouvant, celui de l‘étude de la THRIVE IV l‘applicabilité dans l‘embolisme pulmonaire stabile hémodynamique. Une étude, randomisée, à double anonymat a été exécutée pour comparer Ximelagatran oral à Enoxaparin/Warfarin pour un traitement de 6-mois de la thrombose veineuse aiguë (THRIVE treatment). Une deuxième étude randomisée, à double anonymat a comparé Ximelagatran au placebo plus de 18 mois après une thérapie de l‘anticoagulant de 6 mois de la thrombose profonde. 2 × 36 mg Ximelagatran était aussi efficace et coffre-fort que la thérapie conventionnelle d‘anticoagulant pour une prophylaxie de 6 mois des événements récurrents. 2 × 24 mg Ximelagatran a sensiblement réduit des événements récurrents comparés au placebo sans augmenter le risque hémorragiques. Une augmentation réversible d’ alaninaminotransferase été vue entre les mois 2 et 4. * Ximelagatran ist aktuell in Deutschland für die Thromboembolieprophylaxe in der orthopädischen Chirurgie zugelassen. Für weitere Indikationen ist die Zulassung beantragt. (Anm. d. Red.)

Schlüsselwörter

Venenthrombose - Antikoagulation - Thrombininhibitor - Ximelagatran

Keywords

Venous thrombosis - anticoagulation - thrombin inhibitor - ximelagatran

Mots clés

Thrombose de veine profonde - vitamines K antagoniste - thrombine inhibiteur - Ximelagatran

^* Ximelagatran ist aktuell in Deutschland für die Thromboembolieprophylaxe in der orthopädischen Chirurgie zugelassen. Für weitere Indikationen ist die Zulassung beantragt. (Anm. d. Red.)

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