(Stroke. 1995;26:2219-2221.)
© 1995 American Heart Association, Inc.
Articles |
Treatment of Acute Ischemic Stroke
Challenging the Concept of a Rigid and Universal Time Window
From Institut Nationale de la Santé et de la Recherche Medicale (INSERM) U 320, Centre Cyceron, Caen, France (J.C.B.); Department of Neuroradiology, University of Heidelberg (Germany) (R. von K.); and Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, Calif (G.J. del Z.).
Correspondence to Dr J.C. Baron, Institut Nationale de la Santé et de la Recherche Medicale (INSERM) U 320, Centre Cyceron, Boulevard H. Becquerel, BP 5229, F-14074 Caen Cedex, France.
Key Words: clinical trials • stroke, ischemic • stroke onset
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Introduction |
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Acute stroke treatment has recently become a major area for clinical trials. Each year, thousands of patients with first-ever middle cerebral artery (MCA) territory stroke are enrolled in therapeutic trials, testing the hypothesis that the investigational treatment might improve functional outcome. In addition to trials of therapeutic thrombolysis, other classes of agents such as glutamate antagonists, free radical scavengers, anticytokines, and calcium channel blockers are presently being tested for therapeutic efficacy. Whereas most trials in the 1970s and 1980s enrolled patients within 24 or even 48 hours after stroke onset, at the present time it would be almost unthinkable to extend the time of inclusion beyond the "magic limit" of 6 hours. There are four reasons for this: First, experiments conducted in the nonhuman primate that led to the concept of the ischemic penumbra clearly documented that "time is brain," with apparently only little penumbra remaining beyond 3 hours.1 2 Second, thus far many clinical trials have reported negative, only marginally significant, and/or positive but poorly reproducible findings; late inclusion of patients was considered to be responsible for treatment failure.3 4 Third, recent studies have demonstrated that it is possible to have stroke patients seen in the hospital within 3 to 6 hours after onset.5 6 Fourth, the success of intravenous therapeutic thrombolysis in less than 6 hours after myocardial infarction stimulated a similar design for acute stroke.7
For organizational reasons it has been operationally justified to apply
a rigid time window for screened patients in multicenter, international
trials. Furthermore, it is reasonable
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