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(Stroke. 2001;32:2708.)
© 2001 American Heart Association, Inc.

Controversies in Stroke

Further Randomized Controlled Trials of Tissue Plasminogen Activator Within 3 Hours Are Required

Section Editors: Geoffrey A. Donnan MD, FRACP and Stephen M. Davis MD, FRACPRichard Iain Lindley, MD, FRCP(Edin)

From the Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh, UK.

Correspondence to Dr Richard Iain Lindley, Department of Clinical Neurosciences, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK. E-mail richard.lindley@ed.ac.uk

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

Although early (within 3 hours of onset) tissue plasminogen activator (tPA) has been approved as a treatment for stroke in several countries and endorsed by experts, it remains underused. Clinicians are still uncertain about whom to treat.

Why Are Stroke Physicians Uncertain of the Benefits of Early tPA?

An independent national survey¹ of 1716 stroke physicians in the United Kingdom reported that 74% were uncertain of the benefits of thrombolytic therapies. A recent United States survey² reported that less than half of the responding neurologists had administered tPA and only 30% believed the efficacy of intravenous tPA was "very convincing."

The Available Evidence

The randomized controlled trials (RCTs) of thrombolysis for acute ischemic stroke have been systematically reviewed with data from just over 5000 patients in 17 trials.³ The majority of the data derives from the 8 tPA trials (2955 patients). In the review it was noted that few older patients (aged 80 years) had been included. Unfortunately, there were too few data to perform many subgroup analyses, but overall 3 important conclusions were drawn: (1) there was a definite substantial risk of fatal intracranial hemorrhage; (2) there was a nonsignificant excess of deaths; and (3) these risks appeared to be balanced by an increase in independent survival, which appeared most beneficial for tPA given early (<3 hours after onset).

However, there were too few data to help determine the risk for individual patients. We do not have data on the effects of tPA subdivided by initial CT brain scan appearances, stroke severity, stroke subtype, patient age, or whether the benefits of tPA persist . . . [Full Text of this Article]

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