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(Circulation. 2003;107:2769.)
© 2003 American Heart Association, Inc.

Editorials

Adding to the Effectiveness of Intravenous Tissue Plasminogen Activator for Treating Acute Stroke

James C. Grotta, MD

From the Department of Neurology, UT-STAT Stroke Team, University of Texas-Houston Medical School, Houston.

Correspondence to James C. Grotta, MD, Department of Neurology, UT-STAT Stroke Team, University of Texas-Houston Medical School, 6431 Fannin, MSB 7.001, Houston, TX 77030. E-mail james.c.grotta@uth.tmc.edu

Key Words: Editorials • stroke • plasminogen activators

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

Intravenous tissue plasminogen activator (rt-PA) remains the only approved therapy for acute ischemic stroke with demonstrated effectiveness in phase 3 clinical trials.¹ Unfortunately, the utilization of this treatment is limited by a 6% risk of symptomatic brain hemorrhage² and a brief 3-hour time window of efficacy from symptom onset to treatment.³ Furthermore, its effectiveness is limited for several reasons; intravenously administered rt-PA often fails to lyse large clots,^4,5 arteries reocclude in about a third of cases,⁵ flow may remain stagnant in the microcirculation despite clot lysis,^6,7 and cellular injury may continue despite reperfusion.⁸

See p 2837

Attempts to augment the effect of IV rt-PA have so far been only partially successful. The most promising results have occurred with endovascular techniques that deliver smaller doses of lytic drugs, energy-producing catheters, or mechanical devices directly into the clot to achieve more complete lysis. Pro-urokinase delivered directly into proximal occlusions of the middle cerebral artery on average 5.3 hours after stroke onset was able to achieve lysis in 66% of cases with improved outcome (over heparin alone) in a phase 2 trial.⁹ Similarly, if IV rt-PA is followed by intra-arterially administered rt-PA (average 3.6 hours after stroke onset), complete or partial recanalization occurred in 56% with improved outcome compared with historical placebo-treated controls.¹⁰ Both of these studies need replication with a larger sample and head-to-head comparison against IV rt-PA alone. Studies with various energy-producing and mechanical disruption catheters are just starting. All of these endovascular techniques have the limitations of expense, available expert . . . [Full Text of this Article]

Related Article:

Adjuvant Treatment With a Glycoprotein IIb/IIIa Receptor Inhibitor Increases the Therapeutic Window for Low-Dose Tissue Plasminogen Activator Administration in a Rat Model of Embolic Stroke

Li Zhang, Zheng Gang Zhang, Ruilan Zhang, Daniel Morris, Mei Lu, Barry S. Coller, and Michael Chopp
Circulation 2003 107: 2837-2843. [Abstract] [Full Text]

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