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DOI: 10.1055/s-0037-1616916
Neue Antikoagulanzien
New anticoagulantsPublication History
Publication Date:
29 December 2017 (online)
Zusammenfassung
Dieser Übersichtsartikel referiert den aktuellen Stand der Entwicklungen auf dem Gebiet der neuen Antikoagulanzien. Erläutert werden unterschiedliche Angriffspunkte in der Gerinnungskaskade: Hemmung der Initiationsphase, Faktor-Xa- oder Thrombinhemmung. Der Schwerpunkt liegt bei den Substanzen in fortgeschrittener Entwicklung, die die Phase-II-Studien zur venösen Thromboembolie (VTE)-Prophylaxe als ˶proof of concept“ erfolgreich abgeschlossen haben.
Bei den Faktor-Xa-Inhibitoren ist Fondaparinux als indirekter Hemmer bereits für die Prophylaxe und die Therapie thromboembolischer Erkrankungen sowie das akute Koronarsyndrom zugelassen (OASIS 5 und 6). Rivaroxaban ist der erste direkte Faktor-Xa-Hemmer, für den eine Zulassung für die Indikation VTE-Prophylaxe beantragt wurde. Die erste Studie aus dem RECORD 1–4-Programm wurde abgeschlossen, die Studien zur Therapie von VTE (EINSTEIN) und zur Schlaganfallprophylaxe bei Vorhofflimmern (ROCKET AF) befinden sich in Phase III, Der Einsatz bei akutem Koronarsyndrom wird ebenso wie bei Apixaban in Phase II untersucht. Die ADOPT-Studie mit Apixaban zur VTEPrävention bei internistischen Indikationen und die BOTTICELLI- Studie bei Vorhofflimmern haben Phase III erreicht. Nachdem Ximelagatran zurückgezogen werden musste, ist Dabigatran der am weitesten entwickelte direkte Thrombininhibitor, dessen umfangreiches Phase-III-Programm REVOLUTION vorgestellt wird und der sich für die Indikation VTE-Prophylaxe ebenfalls bereits im Zulassungsverfahren befindet.
Summary
This review updates the latest developments concerning new anticoagulants. It describes potential targets in the coagulation pathway: inhibition of the initiation of coagulation, factor Xa and thrombin inhibitors. The focus is laid on substances in late development that already passed the phase II trial for venous thromboembolism (VTE)-prevention as ˶proof of concept”.
In the group of factor Xa inhibitors, the indirect inhibitor Fondaparinux has got approval for the indications prevention and therapy of VTE and acute coronary syndromes (OASIS 5 and 6). Rivaroxaban is the first direct factor Xa inhibitor that was admitted for approval in the indication VTE-prevention. The first trial of the program RECORD 1–4 was finished, trials for the indications therapy of VTE (EINSTEIN) and stroke prevention in atrial fibrillation (ROCKET AF) are in phase III. The use in acute coronary symptoms is – like apixaban – evaluated in phase II. The ADOPT trial with apixaban for VTE-prevention, as well as the BOTTICELLI trial for atrial fibrillation, have reached phase III. After the withdrawal of Ximelagatran, Dabigatran is the most developed direct thrombin inhibitor, being extensively studied in the comprehensive phase- III-program REVOLUTION and in approval for the indication VTE-prevention.
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