Thrombolysis in acute ischemic stroke: Controlled trials and clinical experience

Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) i s approved in the United States for treatment of acute ischemic stroke. App roval was granted after a large, randomized, placebo-controlled study by th e National Institute of Neurological Disorders and Stroke (NINDS) showed a significant improvement in 3-month outcomes with rtPA despite a significant risk for symptomatic hemorrhage. Two other trials, the first and second Eu ropean Cooperative Acute Stroke Study (ECASS I and II), have shown comparab le results, but neither was statistically positive for the predefined prima ry end point. An analysis of the risk/benefit profile of rtPA therapy based on the results of these three trials indicates that the treatment is effec tive and, when administered within 3 hours of symptom onset at a dose of 0. 9 mg/kg, the benefits by far outweigh the risks for eligible patients. Even with the 6-hour time window of the two ECASS trials, a combined analysis o f the three studies shows the number of disabled or dead patients to be sig nificantly reduced. Preliminary data collected on the use of rtPA outside o f clinical trials in the United States and Europe suggest that, when rtPA i s used according to the trial protocol, the risks and benefits are similar to those observed in clinical trials. However, even within the United State s, rtPA is underutilized, The most substantial treatment barrier is the nar row time window, which may be expanded if long-term experience shows that t his is possible. Most stroke patients arrive at the hospital too late to be eligible for screening and treatment. Education of the public and physicia ns may help to overcome this difficulty.