Alteplase for appropriate stroke patients is safe and effective

Jan 28 2007

The thrombolytic drug alteplase, despite recent concerns, is safe and effective in routine clinical use when used within 3 hours of stroke onset, according to an observational study published in this week's issue of The Lancet.

Alteplase (recombinant tissue plasminogen activator) is currently the only approved medical therapy for patients with acute ischaemic stroke. Intravenous treatment with alteplase within a 3-hour window of stroke onset has been shown to be safe and effective in randomised trials. However, concerns have been raised about the applicability of these data to individuals in daily clinical practice, especially considering the short time within which treatment must be given, and the potential risks of intracerebral haemorrhages when thrombolytic therapy is applied. Alteplase was licensed for the treatment of acute ischaemic stroke in the USA in 1996, and in Canada in 1999. As a requisite of the European Union's conditional license in 2002, a large observational study was required to assess whether the levels of safety of intravenous alteplase, seen in randomised controlled trial populations, could be reproduced in clinical practice.

Nils Wahlgren (Department of Neurology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden) and colleagues established the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST)—a prospective monitored study that enrolled 6483 patients from 285 European Centres (50% with little previous experience in stroke thrombolysis) between 2002 and 2006. Primary outcome measures were the rates of symptomatic intracerebral haemorrhage (SICH) type 2 within 24 hours and 3-month mortality. The results show that the proportion of patients who developed SICH in the SITS-MOST and alteplase randomised controlled trials were much the same. There was, however, a noticeable reduction in mortality within the first 3 months of stroke onset in SITS-MOST compared with that seen in the pooled randomised controlled trials (11·3% vs 17·3%). The findings indicate that intravenous alteplase is safe and effective in routine clinical use even by centres with little previous experience of thrombolytic therapy.

The authors conclude: "Although there are still unanswered questions with regard to the role of stroke thrombolysis beyond the limitations of this study, our data suggest that thrombolysis should now be considered as part of routine care of suitable stroke patients. We hope these findings will encourage the uptake of routine thrombolysis therapy for suitable patients in stroke centers, whether experienced or new to stroke thrombolysis."

In an accompanying Comment, Gregory Albers and Jean-Marc Olivot (Stanford Stroke Centre, Stanford University Medical Centre, CA, USA) state: " SITS-MOST imparts a strong message to European regulators that permanent approval of alteplase for appropriate stroke patients in suitable settings is justified."