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

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. (Stroke. 2009; 40: 2438-2441.)