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(Stroke. 2003;34:359.)
© 2003 American Heart Association, Inc.

Advances in Stroke 2002

Emerging Therapies for Acute Ischemic Stroke

New Therapies on Trial

Marc Fisher, MD Thomas G. Brott, MD

From the Department of Neurology, University of Massachusetts Medical School, Worcester, Mass (M.F.), and the Department of Neurology, Mayo Medical School, Jacksonville, Fla (T.G.B.).

Correspondence to Marc Fisher, MD, UMASS/Memorial Healthcare, 119 Belmont St, Worcester, MA 01605. E-mail fisherm@ummhc.org

Key Words: acute stroke trials • stroke • thrombolysis

An extract of the first 250 words of the full text is provided, because this article has no abstract.

The development of additional effective therapies for acute ischemic stroke remains a challenging but critical endeavor. Intravenous recombinant tissue plasminogen activator (rtPA) initiated within 3 hours of stroke onset remains the only approved and validated therapy for acute ischemic stroke, and regulatory approval has expanded recently. Many other therapies have been evaluated, and these trials have either been inconclusive or negative.¹ These acute stroke trials do provide valuable information concerning how to implement future trials and some glimmers of hope about existing data. Some of the lessons learned from prior acute stroke trials that will help to guide future trials are outlined below. The two fundamental approaches to the development of acute stroke therapy remain reperfusion and neuroprotection. This short review will focus on the current status of both approaches and how they might be combined, hopefully in the near future.

Negative acute stroke treatment trials may be explained by the following:

1. The agents evaluated in clinical trials may not have been adequately tested in preclinical studies to provide robust confirmation of efficacy in appropriate animal models.
   
2. Side effects precluded adequate drug assessment or did not allow use of adequate drug concentrations.
   
3. Because of macro-occlusions and, perhaps, micro-occlusions, the drug did not penetrate into or beyond the penumbral tissue in adequate concentrations.
   
4. Trials included patients not appropriate for the purported mechanism of action of the drug being tested.
   
5. Patients were included too late after stoke onset to allow for adequate assessment of the drug’s efficacy, and imaging studies were not . . . [Full Text of this Article]

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