Systemische Thrombolyse beim akuten ischämischen Schlaganfall: Retrospektiver Vergleich von Patienten mit Indikationsstellung innerhalb vs. außerhalb der Zulassungskriterien

Zusammenfassung

Hintergrund und Ziel: Die systemische Thrombolyse mit rt-PA und die Behandlung auf der Stroke Unit sind evidenzbasierte Therapiestrategien in der Akutphase des ischämischen Schlaganfalls. Im Untersuchungszeitraum wurden dabei im Sinne individueller Heilversuche auch Lyse-Therapien jenseits der Zulassungskriterien vorgenommen. Ziel dieser Studie war es zu prüfen, ob und in welchem Ausmaß sich das klinische Ergebnis (objektivierbar in der National Institutes of Health Stroke Scale, NIHSS) am Folgetag nach Thrombolyse bei gemäß vs. außerhalb der Zulassungskriterien therapierten Patienten unterscheidet.

Methoden: Es wurden in einer 1:1 gematchten Kohortenstudie retrospektiv 52 Index-Patienten (mit Zulassungsüberschreitung) mit 52 Match-Patienten (Lyse gemäß Zulassungskriterien) verglichen. Als Match-Kriterien galten das Alter und der Aufnahme-NIHSS der Patienten. Sofern eines der beiden Übereinstimmungskriterien die Zulassungsüberschreitung darstellte, wurde nur nach dem verbleibenden Kriterium gematcht. Primärer Endpunkt der Studie war die intraindividuelle Änderung des NHISS einen Tag nach gegenüber vor Lyse. Die konfirmatorische Auswertung erfolgte mit einem 2-seitigen Vorzeichentest zum 5%-Niveau. Um hierfür eine statistische Power von 80% zu sichern, wurden 52 matched pairs dokumentiert.

Ergebnisse: Der Vergleich der Gesamtveränderung im NIHSS zwischen außerhalb vs. innerhalb der Zulassungskriterien therapierten Patienten zeigte keinen signifikanten Unterschied (Vorzeichentest p=0,568). Die Verminderung des NIHSS war bei den Match-Patienten im Median um 0,5 Punkte größer. Demnach war die Veränderung der klinischen Symptomatik bei innerhalb vs. außerhalb der Zulassungskriterien therapierten Patienten im Median nicht unterschiedlich ausgeprägt.

Schlussfolgerung: Es konnte kein signifikanter Unterschied im primären Endpunkt, dem klinischen Ergebnis am Folgetag nach Lyse, festgestellt werden zwischen Patienten mit Zulassungs-gerechter respektive -erweiterter Lyse-Therapie. Die Studienergebnisse bestärken das klinische Vorgehen, bei jedem Patienten nach sorgfältiger Nutzen-Risiko-Analyse eine individuell abgestimmte Therapie-Entscheidung zu treffen.

Abstract

Background and Intention: Systemic thrombolysis with rt-PA and treatment on neurological stroke units are evidence-based therapy strategies during the acute phase of ischemic stroke. In individual cases, thrombolytic therapy was used beyond the licensed criteria. The intention of this study was to investigate whether and to which extent the clinical outcome (assessed by means of the National Institutes of Health Stroke Scale, NIHSS) on the first day after thrombolysis would differ between patients treated with thrombolysis according to vs. beyond the licensed criteria.

Material and Methods: In a retrospective 1:1 matched pair design 52 index patients (treated beyond the licensed criteria) have been compared to 52 matched patients who had been treated generally according to the licensed criteria. Matching criteria were the patient’s age and the first NIHSS noted in the emergency room. If one of these matching criteria was the reason why the treatment was considered beyond the licensed criteria, only the remaining matching criterion was applied. The primary endpoint of this investigation was the intra-individual change of the NHISS one day after vs. before thrombolysis; the confirmatory analysis was based on a 2-sided sign test at the 5% significance level. To ensure a statistical power of 80%, 52 matched pairs were documented.

Results: The comparison of the total change in the NIHSS in patients treated beyond vs. according to the licensed criteria showed no significant difference (sign test p = 0,568). Among the matched patients the decrease of the NIHSS was higher than in the index patient cohort (in median 0,5 points); the changes in clinical symptom profiles were not found to differ among the cohorts.

Conclusion: No significant difference could be determined in the clinical outcome at the subsequent day to thrombolysis between patients treated according to and beyond the licensing criteria. This supports the clinical practice to personalize the therapy decision after having carefully reflected possible benefit and risk profiles for thrombolysis.

Schlüsselwörter

Schlaganfall - systemische Thrombolyse - rt-PA - off label - Kontraindikation

Keywords

stroke - systemic thrombolysis - rt-PA - off-label - contraindication

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