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Neue orale Antikoagulanzien beim Vorhofflimmern

New oral anticoagulants in atrial fibrillation

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Zusammenfassung

Vorhofflimmern (VHF) verursacht mindestens 20% aller ischämischen Schlaganfälle. In großen randomisierten Primär- und Sekundärprophylaxestudien schützte die orale Antikoagulation (OAK) mit Vitamin-K-Antagonisten (VKA) wesentlich wirksamer als Thrombozytenaggregationshemmer vor Schlaganfällen. Aufgrund der problematischen pharmakologischen Eigenschaften der VKA werden aber zu wenige VHF-Patienten mit OAK behandelt. Die gezielte Entwicklung spezifisch an den zentralen Gerinnungsfaktoren Thrombin und Faktor Xa ansetzender oraler Inhibitoren ermöglicht eine zuverlässige Antikoagulation ohne regelmäßiges Gerinnungsmonitoring. In der vorliegenden Übersicht werden zunächst die pharmakologischen Eigenschaften der verschiedenen Thrombin- und Faktor-Xa-Inhibitoren verglichen. Von den vier großen randomisierten Phase-III-Studien bei VHF (RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) mit dem primären Wirksamkeitsendpunkt Schlaganfall weisen die bereits publizierten Daten der RELY-Studie auf eine überlegene Wirksamkeit von Dabigatranetexilat (2-mal 150 mg/Tag) bei signifikant niedrigerem Hirnblutungsrisiko gegenüber Warfarin hin. Ähnlich günstige Ergebnisse ergeben sich aus vorläufigen Daten zu Rivaroxaban. Apixaban war in der AVERROES-Studie wirksamer als Acetylsalicylsäure bei vergleichbarem Blutungsrisiko. Damit deutet sich ein insgesamt günstiges Nutzen-Risiko-Verhältnis für die neuen Substanzen bei größerem Patientenkomfort an. Noch ungelöste Fragen betreffen die Prüfung der Patientenadhärenz durch geeignete Gerinnungstests sowie die Notfallgerinnungsdiagnostik und -therapie bei ischämischen und hämorrhagischen Schlaganfällen unter neuen OAK.

Summary

Atrial fibrillation (AF) causes at least 20% of all ischemic strokes. In large randomized trials of primary and secondary stroke prevention, anticoagulation with vitamin K antagonists (VKA) protected much more efficiently than antiplatelet agents against stroke. Because of the problematic pharmacological properties of VKA only part of the AF patients are currently being treated with oral anticoagulants (OAK). The targeted development of specific oral inhibitors of the central coagulation factors thrombin and factor Xa allows reliable anticoagulation without regular coagulation monitoring. In the present review, pharmacological properties of the different agents are compared. Of the four large randomized phase 3 studies in AF (RELY, ROCKET-AF, ARISTOTLE, ENGAGE-AF) with the primary efficacy endpoint stroke and systemic embolism, the published data from the RELY trial indicate a superior efficacy of dabigatran etexilate (2×150 mg/day) and a lower risk of intracranial hemorrhage compared to warfarin. Favorable preliminary results have been demonstrated for the factor Xa inhibitor rivaroxaban. Apixaban was more efficacious than ASA and had a similar risk of hemorrhage in the AVERROES study. Thus, the available data suggest a favorable benefit-risk ratio for the new substances in addition to improved patient comfort. Currently unresolved issues relate to the verification of patient adherence by suitable coagulation tests and to the emergency coagulation diagnostics and therapy in acute ischemic or hemorrhagic strokes under the new OAC.

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Danksagung

Die Autoren danken Herrn PD. Dr. Peter Ringleb, Heidelberg, für eine kritische Durchsicht des Manuskripts.

Interessenkonflikt

Der korrespondierende Autor weist auf folgende Beziehungen hin: R.V. wird unterstützt durch ein Else Kröner Memorial Stipendium und hat Honorare für Vorträge, Beratung bzw. Forschungsunterstützung von den Firmen Bayer, Boehringer Ingelheim und SanofiAventis erhalten. W.H. hat Honorare für Vorträge, Beratung bzw. Forschungsunterstützung u. a. von den Firmen Bayer, Boehringer Ingelheim und SanofiAventis erhalten.

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Correspondence to R. Veltkamp.

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Veltkamp, R., Hacke, W. Neue orale Antikoagulanzien beim Vorhofflimmern. Nervenarzt 82, 180–189 (2011). https://doi.org/10.1007/s00115-010-3114-5

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