Antithrombotische Therapien zur Schlaganfallprävention bei Patienten mit kardioembolischem Schlaganfall – Gegenwart und Zukunft

Zusammenfassung

Vorhofflimmern ist ein wichtiger Risikofaktor für Schlaganfälle. Bei Patienten mit absoluter Arrhythmie ist das Schlaganfallrisiko um den Faktor 5 erhöht. Sowohl in der Primär- wie in der Sekundärprävention kann durch eine orale Antikoagulation das relative Schlaganfallrisiko gegenüber Placebo um 60–70 % verringert werden. Orale Vitamin-K-Antagonisten haben eine Reihe von Nachteilen. Es gibt eine Reihe von genetischen Faktoren, die den Metabolismus bestimmen und dazu führen können, dass es bei einigen Patienten sehr schwierig ist, die INR-Werte im therapeutischen Bereich zwischen 2,0 und 3,0 zu halten. Darüber hinaus gibt es eine Vielzahl von Interaktionen mit Nahrungsmitteln und mit anderen Medikamenten, sodass Patienten unter einer Therapie mit Vitamin-K-Antagonisten engmaschig überwacht werden müssen. Bei Patienten mit Kontraindikationen für orale Vitamin-K-Antagonisten kann durch die Gabe von Azetylsalizylsäure das relative Schlaganfallrisiko immer noch um durchschnittlich 22 % gesenkt werden. Die Kombination von Azetylsalizylsäure und Clopidogrel ist gegenüber einer Azetylsalizylsäure-Monotherapie signifikant wirksamer in der Verhinderung ischämischer Schlaganfälle, führt aber gleichzeitig zu einer signifikant erhöhten Blutungsrate. Derzeit gibt es 2 neue Therapieansätze mit oralen Antikoagulanzien, die ganz überwiegend die Nachteile von Vitamin-K-Antagonisten nicht haben. Dazu gehören Antagonisten des Faktors Xa wie Rivaroxaban, Apixaban, Betrixaban, LY517717, YM150 und GU167b oder Faktor-IIa-Inhibitoren (direkte Thrombininhibitoren). Von den direkten Thrombininhibitoren war Ximelagatran in der Schlaganfallprävention bei Patienten mit Vorhofflimmern genauso wirksam wie Warfarin und hatte eine etwas niedrigere Rate an Blutungskomplikationen. Die Substanz musste aber wegen Leberschäden vom Markt genommen werden. Ein weiterer oraler direkter Thrombinantagonist Dabigatran befindet sich im Moment im Endstadium der klinischen Prüfung.

Abstract

Atrial fibrillation is a risk factor for stroke. For patients with absolute arrhythmia, the stroke risk is increased by 5. Both in primary and secondary prevention, the relative risk of stroke compared with placebo is reduced by 60–70 % by oral anticoagulation. However, oral vitamin K antagonists have disadvantages. There are some genetic factors that control the metabolism and can lead to situations in which it is difficult für some patients to keep the INR value in the therapeutic range between 2.0 and 3.0. Furthermore, there are numerous interactions with food and other drugs so that patients must be closely monitored. In patients with contraindications for oral vitamin K antagonists the relative risk of stroke can still be reduced by 22 % on average by administration of ASA. The combination of ASA and clopidogrel is more effective than ASA alone in reducing ischaemic stroke but concomitantly leads to significantly increased bleeding incidence. At present there are 2 new therapeutic options for oral anticoagulation that do not exhibit most of the disadvantages of vitamin K antagonists. These include antagonists of factor Xa such as rivaroxaban, apixaban, betrixaban, LY517717, YM150 and GU167b or factor IIa inhibitors (direct thrombin inhibitors). Of the latter, ximelagatran was equally effective in stroke prevention in patients with atrial fibrillation as warfarin and had a somewhat lower rate of bleeding complications. However, the substance had to be removed from the market due to liver damage. Another oral direct thrombin inhibitor, dabigatran, is currently in the final phase of clinical testing.

Schlüsselwörter

Vorhofflimmern - Schlaganfall - orale Antikoagulation - Thrombozytenfunktionshemmer - Prävention

Keywords

atrial fibrillation - stroke - oral anticoagulation - antiplatelet drugs - prevention

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