This Article Full Text Full Text (PDF) CME: Take the course for this article: Stroke: July 2009, Volume 40, Number 7 All Versions of this Article: 40/7/2438    most recent STROKEAHA.109.552547v1 Alert me when this article is cited Alert me if a correction is posted 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 Google Scholar Articles by Lansberg, M. G. Articles by Thijs, V. N. PubMed PubMed Citation Articles by Lansberg, M. G. Articles by Thijs, V. N. Related Collections Acute Cerebral Infarction Emergency treatment of Stroke Thrombolysis

(Stroke. 2009;40:2438.)
© 2009 American Heart Association, Inc.

Original Contributions

Efficacy and Safety of Tissue Plasminogen Activator 3 to 4.5 Hours After Acute Ischemic Stroke

A Metaanalysis

Maarten G. Lansberg, MD, PhD; Erich Bluhmki, PhD Vincent N. Thijs, MD, PhD

From the Stanford Stroke Center (M.G.L.), Stanford University Medical Center, Palo Alto, Calif; the Department of Neurology (V.N.T.), University Hospitals of Leuven, Belgium; the Vesalius Research Center (V.N.T.), Leuven, Belgium; and Boehringer Ingelheim Pharma GmbH & Co (E.B.), Germany.

Correspondence to Maarten G. Lansberg, Stanford Stroke Center, 701 Welch Road, Suite B325, Palo Alto, CA 94304-9705, USA. E-mail lansberg{at}stanford.edu

Background and Purpose— The Third European Cooperative Acute Stroke Study (ECASS-3) demonstrated a benefit of treatment with intravenous tissue plasminogen activator (tPA) for acute stroke in the 3- to 4.5-hour time-window. Prior studies, however, have failed to demonstrate a significant benefit of tPA for patients treated beyond 3 hours. The purpose of this study was to produce reliable and precise estimates of the treatment effect of tPA by pooling data from all relevant studies.

Methods— A metaanalysis was undertaken to determine the efficacy of tPA in the 3- to 4.5-hour time-window. The effect of tPA on favorable outcome and mortality was assessed.

Results— The metaanalysis included data from patients treated in the 3- to 4.5-hour time-window in ECASS-1 (n=234), ECASS-2 (n=265), ECASS-3 (n=821) and The Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) (n=302). tPA treatment was associated with an increased chance of favorable outcome (odds ratio 1.31; 95% CI: 1.10 to 1.56; P=0.002) and no significant difference in mortality (odds ratio 1.04; 95% CI: 0.75 to 1.43; P=0.83) compared to placebo treated patients.

Conclusions— Treatment with tPA in the 3- to 4.5-hour time-window is beneficial. It results in an increased rate of favorable outcome without adversely affecting mortality.

Key Words: acute stroke • thrombolysis • metaanalysis