Objectives: (1) To determine whether and how outcome measurements in the ECASS trial are influenced by a shorter time window (0–3 vs. 3–6 h) between onset of symptoms and start of thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA) in acute ischemic stroke. (2) To discuss the results of the ECASS 0- to 3-hour cohort with the results of the National Institute of Neurological Disorders and Stroke Study (NINDSS). Design and Analysis: Analysis of the 0- to 3-hour and the 3- to 6-hour cohort in accordance with the ECASS protocol. Comparative analysis of the ECASS and NINDSS results following the NINDSS protocol using dichotomized endpoints. Main Outcome Measures: Primary endpoints: modified Rankin Scale, Barthel Index; secondary endpoints: combined Barthel/Rankin, long-term Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, mortality at 30 and 90 days, occurrence of intracranial hemorrhage. NINDS trial endpoint: favorable outcome as defined in the NINDS trial. Results: In ECASS, 87 patients were randomized within 3 h of stroke onset. Differences in favor of rt-PA treatment can be found for all primary and secondary outcome measures in the ECASS 0- to 3-hour cohort, except for mortality at day 30, which is somewhat higher in the rt-pA-treated group. However, due to the small sample size, the differences do not reach statistical significance. Early infarct signs (as defined by the ECASS protocol) are found as early as 2 h after stroke onset. Parenchymal hemorrhages are found significantly more often among rt-PA-treated patients. The results in the ECASS 0- to 3-hour cohort fit well with the results in NINDSS. Conclusion: Data from the 3-hour ECASS cohort support the efficacy of early thrombolytic therapy in acute hemispheric stroke patients. Comparing bleeding complications between the ECASS and NINDSS is difficult because of differences in the definition and occurrence of hemorrhagic events.

Keywords:
Stroke, Thrombolysis, ECASS, rt-PA, Time window
1.
Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boysen G, Bluhmki E, Höxter G, Mahagne M-H: Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke: The European Cooperative Acute Stroke Study (ECASS). JAMA 1995;274:1017–1025.
2.
NINDS rt-PA Stroke Study Group: Tissue plasminogen activator for acute ischemic stroke. N Engl J Med 1995;333:1581–1587.
3.
Donnan GA, Davis SM, Chambers BR, Gates PC, Hankey GJ, McNeil JJ, Rosen D, Stewart-Wynne EG, Tuck RR, for the Australian Streptokinase (ASK) Trial Group: Streptokinase for acute ischemic stroke with relationship to time of administration. JAMA 1996;25:961–966.
4.
Multicentre Acute Stroke Trial-Italy (MAST-I) Group: Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Lancet 1995;345:1509–1515.
5.
The Multicenter Acute Stroke Trial-Europe Study Group: Thrombolytic therapy with streptokinase in acute ischemic stroke. N Engl J Med 1996;335:145–150.
6.
Boysen G, Hacke W: European Cooperative Acute Stroke Study (ECASS): Study design and progress report. Eur J Neurol 1995;1:213–219.
7.
Tilley BC, Marler J, Geller NL, Lu M, Legler J, Brott T, Lyden P, Grotta J, for the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trial Group: Use of global test for multiple outcomes in stroke trials with application to the National Institute of Neurological Disorders and Stroke rt-PA Stroke Trial. Stroke 1996;27:2136–2142.
8.
von Kummer R, Bozzao L, Manelfe C: Early CT Diagnosis of Hemispheric Brain Infarction. Berlin, Springer, 1995.
9.
von Kummer R, Meyding-Lamade U, Forsting ML, Rosin L, Ricke K, Hacke W, Sartor K: Sensitivity and prognostic value of early CT in occlusion of the middle cerebral artery trunk. AJNR 1994;15:9–15.
10.
Baron JC, von Kummer R, del Zoppo GJ: Treatment of acute ischemic stroke: Challenging the concept of a rigid and universal time window. Stroke 1995;26:2219–2221.
11.
Toni D, Fiorelli M, Gentile M, Bastianello S, Sachetti ML, Argentino C, Pozzilli C, Fieschi C: Progressing neurological deficit secondary to acute ischemic stroke: A study on predictability, pathogenesis and prognosis. Arch Neurol 1995;52:670–675.
1998
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.