Systemische Thrombolysetherapie des akuten Hirninfarktes: Kaum noch Platz für Zweifel

 

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Zusammenfassung

Die Zulassung von rt-PA zur Behandlung der akuten zerebralen Ischämie im 3-Stunden-Zeitfenster stützte sich bislang im Wesentlichen auf den 2. Teil der 1995 publizierten NINDS-Studie mit 333 Patienten. Im 3–6-Stunden-Zeitfenster konnte bislang keine Thrombolysestudie per se die Effektivität von rt-PA nachweisen. Allerdings erbrachte die kombinierte Analyse 6 systemischer Thrombolysestudien (NINDS, ECASS, ATLANTIS; n = 2 775) deutliche Hinweise auf das Vorliegen einer rt-PA-Effektivität bis zu 4,5 Stunden nach Symptombeginn ohne relevante Auswirkung auf die Rate von Blutungskomplikationen. Die Zulassung von rt-PA in Europa war an die Führung eines Thrombolyseregisters geknüpft (SITS-MOST). Hierin konnte die Sicherheit und Effektivität der rt-PA-Therapie an 6 483 behandelten Patienten eindrücklich bestätigt werden. Darüber hinaus forderte die europäische Zulassungsbehörde eine randomisierte Patientenstudie mit einem Zeitfenster über 3 Stunden. Die hierfür konzipierte Studie (ECASS3) konnte an 821 eingeschlossenen Patienten die Effektivität und Sicherheit auch im Zeitfenster zwischen 3 und 4,5 Stunden nachweisen. Das heißt umgekehrt allerdings nicht, dass man nun mehr Zeit hat, Patienten mit einem ischämischen Schlaganfall zu behandeln. Weiterhin gilt, dass die Behandlung mit rt-PA so früh wie möglich initiiert werden muss, um dem Patienten die größtmögliche Chance auf ein gutes Outcome zu geben.

Abstract

So far, the approval of rt-PA for the treatment of acute ischemic stroke within a 3-hour time window was based essentially on the second part of the 1995 published NINDS trial which enrolled 333 patients. For the time window between 3 and 6 hours after stroke onset, so far no single rt-PA trial has proved any efficacy. However, the combined analysis of six thrombolysis trials (NINDS, ECASS, ATLANTIS, n = 2 775) strongly indicated an efficacy of rt-PA for up to 4.5 hours, with no significant increase in bleeding complications. The European Evaluation of Medicines Agency (EMEA) granted limited approval for rt-PA in 2002. Limitation one was the request for an observational safety study. Subsequently, the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) was undertaken. SITS-MOST enrolled 6 483 patients and could convincingly confirm the safety and efficacy of rt-PA. Limitation two was the request for a randomised controlled trial with rt-PA beyond the 3-hour time window. The trial conceived for this request – ECASS3 – convincingly proved the efficacy and safety for rt-PA administered between 3 and 4.5 hours after stroke onset. However, this does not mean that there is more time for stroke teams to treat acute ischemic stroke patients. To give patients the best possible chance for a good clinical outcome it remains essential to start rt-PA treatment as soon as possible.

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Dr. Andreas Hug

Neurologische Universitätsklinik Heidelberg

Im Neuenheimer Feld 400

69120 Heidelberg

Email: Andreas.Hug@med.uni-heidelberg.de