The 4.5-hour time window for intravenous thrombolysis with intravenous tissue-type plasminogen activator is not firmly established.

Most stroke neurologists would likely choose to treat this patient with intravenous tissue-type plasminogen activator (IV tPA) assuming the treatment could be initiated within 4.5 hours from stroke onset. In fact, the American Heart Association and European Stroke Organization guidelines both recommend treatment of selected patients in the 3- to 4.5-hour time window. IV tPA is approved in this time window in 15 countries in Europe and several other countries around the world. In the United States, however, the Food and Drug Administration declined an application by Genentech to extend the time window for treatment beyond 3 hours. The evidence supporting the benefit of treatment in the 3- to 4.5-hour time window includes the results of European Cooperative Acute Stroke Study (ECASS) III,1 a randomized controlled trial enrolling 821 patients. Three prior randomized controlled trials (ECASS, ECASS II, Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke [ATLANTIS]) and 1 subsequent trial (Third International Stroke Trial [IST-3]) attempting to extend the time window for IV tPA beyond 3 hours failed to show significant benefit. In addition, an updated meta-analysis of 7012 patients in 12 IV tPA trials found that the major benefit occurred in patients treated within 3 hours with no significant effect of IV tPA in almost 5000 patients treated 3 to 6 hours after stroke onset (odds ratio, 1.07; 95% confidence interval, …