TY - JOUR
T1 - Thrombolysis in acute ischemic stroke
T2 - Controlled trials and clinical experience
AU - Hacke, Werner
AU - Brott, Thomas
AU - Caplan, Louis
AU - Meier, Dieter
AU - Fieschi, Cesare
AU - Von Kummer, Rüdiger
AU - Donnan, Geoffrey
AU - Heiss, Wolf Dieter
AU - Wahlgren, Nils Gunnar
AU - Spranger, Matthias
AU - Boysen, Gudrun
AU - Marler, John R.
PY - 1999
Y1 - 1999
N2 - Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) is approved in the United States for treatment of acute ischemic stroke. Approval was granted after a large, randomized, placebo-controlled study by the 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 European Cooperative Acute Stroke Study (ECASS I and II), have shown comparable results, but neither was statistically positive for the predefined primary 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 effective 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 of the three studies shows the number of disabled or dead patients to be significantly reduced. Preliminary data collected on the use of rtPA outside of clinical trials in the United States and Europe suggest that, when rtPA is used according to the trial protocol, the risks and benefits are similar to those observed in clinical trials. However, even within the United States, rtPA is underutilized. The most substantial treatment barrier is the narrow time window, which may be expanded if long-term experience shows that this is possible. Most stroke patients arrive at the hospital too late to be eligible for screening and treatment. Education of the public and physicians may help to overcome this difficulty.
AB - Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) is approved in the United States for treatment of acute ischemic stroke. Approval was granted after a large, randomized, placebo-controlled study by the 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 European Cooperative Acute Stroke Study (ECASS I and II), have shown comparable results, but neither was statistically positive for the predefined primary 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 effective 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 of the three studies shows the number of disabled or dead patients to be significantly reduced. Preliminary data collected on the use of rtPA outside of clinical trials in the United States and Europe suggest that, when rtPA is used according to the trial protocol, the risks and benefits are similar to those observed in clinical trials. However, even within the United States, rtPA is underutilized. The most substantial treatment barrier is the narrow time window, which may be expanded if long-term experience shows that this is possible. Most stroke patients arrive at the hospital too late to be eligible for screening and treatment. Education of the public and physicians may help to overcome this difficulty.
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M3 - Review article
C2 - 10532643
AN - SCOPUS:0032744573
SN - 0028-3878
VL - 53
SP - S3-S14
JO - Neurology
JF - Neurology
IS - 7 SUPPL. 4
ER -