The Impact of the Extended Time Window Seen in the ECASS III Trial on the Guidelines for Stroke Management in Europe

Original Manuscript

The Impact of the Extended Time Window Seen in the ECASS III Trial on the Guidelines for Stroke Management in Europe

Keith W. Muir^1,2

Affiliations: ¹Division of Clinical Neurosciences, University of Glasgow, Glasgow, Scotland, UK; ²Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, Scotland, UK

Submission date: 1st September 2009, Revision date: 5th September 2009, Acceptance date: 9th August 2009

 
ABSTRACT

Pooled analysis from the major randomized controlled trials of intravenous treatment with the recombinant tissue plasminogen activator alteplase for acute ischemic stroke showed a time-dependent benefit. Individual trials used windows of between 3 and 6 h from symptom onset and individually had only been conclusive for treatment within 3 h. The pooled analysis indicated that a significant improvement in the proportion of patients making an excellent recovery might extend to 4.5 h. The ECASS III trial recently confirmed benefit in the 3 to 4.5 h time window, with odds of excellent outcome of around 1.40, in line with predictions. There was no increase in risk of bleeding. Confirmation of safety in practice came from the Safe Implementation of Thrombolysis in Stroke–International Stroke Thrombolysis Register (SITS-ISTR) analysis of patients treated between 3 and 4.5 h. In response to these data, European and other guidelines have been updated to recommend treatment in patients up to 4.5 h after onset of symptoms who otherwise fulfill current European license terms. A formal change in licensed indications is awaited.

Keywords: stroke, cerebrovascular disease, guidelines, thrombolysis, alteplase, recombinant tissue plasminogen activator, rt-PA, acute treatment
Correspondence: Professor Keith Muir, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, Scotland, UK. Tel.: +44-141-201-2494; fax: +44-141-201-2510; e-mail: k.muir@clinmed.gla.ac.uk