Intravenous Tissue Plasminogen Activator for Stroke: A Review of the ECASS III Results in Relation to Prior Clinical Trials

Background: Intravenous tissue plasminogen activator (IV tPA) is currently approved by the Food and Drug Administration for use in acute ischemic stroke patients up to 3 h from symptom onset, based primarily on the National Institute of Neurological Disorders and Stroke tPA trials published in 1995. The most recent trial published with IV tPA in stroke (European Cooperative Acute Stroke Study [ECASS] III) studied patients between 3 and 4.5 h from symptom onset and found a benefit to treatment in the rate of favorable outcome when compared to placebo, with no difference in mortality. Objectives: To examine the patient selection criteria and primary outcomes in ECASS III as compared to prior clinical trials and the current practice in the United States to determine how these new data could be applied to clinical practice. Discussion: With the exception of the longer time from symptom onset to treatment, ECASS III used more restrictive patient selection criteria than is the current practice in the United States to determine patient eligibility for IV tPA. Conclusions: Based on the combined data from all trials, the benefits of thrombolysis with IV tPA for acute ischemic stroke outweigh the risks of treatment for selected patients up to 4.5 h from symptom onset. It is already known that thrombolysis is not beneficial for all stroke patients and strict criteria should be applied before treatment. As time from symptom onset increases, the need for careful patient selection likely also increases.