This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lyden, P. D. Search for Related Content PubMed PubMed Citation Articles by Lyden, P. D.

(Stroke. 2001;32:2709.)
© 2001 American Heart Association, Inc.

Controversies in Stroke

Further Randomized Controlled Trials of tPA Within 3 Hours Are Required—NOT!

Patrick D. Lyden, MD

From the School of Medicine, University of California–San Diego.

Correspondence to Dr Patrick D. Lyden, UCSD School of Medicine, OPC Third Floor, Suite 3, 200 West Arbor Dr, San Diego, CA 92103-8466. E-mail plyden@ucsd.edu

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

Intravenous thrombolysis is beneficial for patients with acute ischemic stroke: in 5 separate trials, treated patients improved more than placebo patients. The first 2 trials, the NINDS trials, were published in 1995 and led directly to the licensing of recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke. In these trials, patients were treated within 90 or 180 minutes of stroke onset with 0.9 mg/kg rtPA after a careful selection procedure. Treated patients enjoyed a near-total resolution of deficit more often (30% to 50% relative benefit) compared with placebo. Symptomatic hemorrhage occurred in 6.4% of treated patients. It is not widely appreciated that in addition to the treated patients who totally cleared their symptoms, an additional 20% to 30% enjoyed a partial improvement.¹ A similar trial utilized intravenous ancrod, a defibrinogenating agent that causes modest thrombolysis, hypofibrinogenemia, and mild anticoagulation.² Benefits and risks were similar to those with rtPA. In the PROACT II study, patients thrombolysed within 6 hours of symptom onset did well, with an acceptable hemorrhage rate.³ Finally, a large European trial of rtPA showed a clear benefit for rtPA, using the analysis method devised for the NINDS trials.⁴

The limitations on this therapy—the only proven stroke treatment—are legendary: patients must be treated promptly after stroke onset, must have no contraindications to thrombolysis, and must be treated by a team skilled in preventing potential complications. Much has been made of these limitations, to the point of considerable nihilism among neurologists. Yet, results similar to the NINDS data are . . . [Full Text of this Article]

This article has been cited by other articles:

				P. A. Lapchak, M.-K. Han, K. F. Salgado, J. Streeter, and J. A. Zivin Safety Profile of Transcranial Near-Infrared Laser Therapy Administered in Combination With Thrombolytic Therapy to Embolized Rabbits Stroke, November 1, 2008; 39(11): 3073 - 3078. [Abstract] [Full Text] [PDF]

				J.M. Wardlaw, P.A.G. Sandercock, and E. Berge Thrombolytic Therapy With Recombinant Tissue Plasminogen Activator for Acute Ischemic Stroke: Where Do We Go From Here? A Cumulative Meta-Analysis Stroke, June 1, 2003; 34(6): 1437 - 1442. [Abstract] [Full Text] [PDF]