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(Stroke. 2001;32:2710.)
© 2001 American Heart Association, Inc.

Controversies in Stroke

When Is Enough Enough?

Geoffrey A. Donnan, MD, FRACP Stephen M. Davis, MD, FRACP

From the National Stroke Research Institute, Heidelberg West, Victoria, Australia.

Correspondence to Prof Goeffrey A. Donnan, National Stroke Research Institute, Level 1, Neurosciences Bldg, Banksia St. Heidelberg West, Victoria 3081, Australia.

Key Words: randomized controlled trials • stroke, acute • stroke, ischemic • thrombolysis • tissue plasminogen activator

We find it fascinating that the views expressed by the protagonists of our first controversy reflect the trans-Atlantic dichotomy of opinion concerning the use of tissue plasminogen activator (tPA). As most clinicians know, tPA is now licensed in North America (United States since 1996) and a number of South American countries. Licensing has been slower in Europe, Australasia, and Asia. Indeed, there is only restricted licensing in a limited number of countries outside North America.

Perhaps understandably, the use of tPA has been taken up more enthusiastically in the United States where the only unequivocally positive trial(s) of therapy was conducted and, importantly, under the auspices of their national funding body. The main difficulty is that an equivalent trial with a 3-hour time window has not been conducted elsewhere, although the cumulative meta-analysis supports the findings of the NINDS trial. Of importance, open phase IV studies with tPA indicate that the positive benefit/risk ratio of the NINDS trial may be replicated, provided that the therapy is administered in expert centers with strict adherence to the NINDS protocol.

Given our current dependence on evidence based medicine, investigators only wish to advocate a therapy when it is of proven value. Only a few thousand patients have been enrolled in tPA stroke trials. In contrast, tens of thousands of patients were studied in the mega-trials of myocardial infarction before thrombolysis became accepted. This may be because the single end point of mortality in myocardial infarction necessitates larger sample sizes than stroke trials, where . . . [Full Text of this Article]

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