Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke
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Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke. / Hacke, Werner; Kaste, Markku; Bluhmki, Erich; Brozman, Miroslav; Dávalos, Antoni; Guidetti, Donata; Larrue, Vincent; Lees, Kennedy R; Medeghri, Zakaria; Machnig, Thomas; Schneider, Dietmar; von Kummer, Rüdiger; Wahlgren, Nils; Toni, Danilo; ECASS Investigators ; Iversen, Helle Klingenberg.
In: New England Journal of Medicine, Vol. 359, No. 13, 25.09.2008, p. 1317-29.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke
AU - Hacke, Werner
AU - Kaste, Markku
AU - Bluhmki, Erich
AU - Brozman, Miroslav
AU - Dávalos, Antoni
AU - Guidetti, Donata
AU - Larrue, Vincent
AU - Lees, Kennedy R
AU - Medeghri, Zakaria
AU - Machnig, Thomas
AU - Schneider, Dietmar
AU - von Kummer, Rüdiger
AU - Wahlgren, Nils
AU - Toni, Danilo
AU - ECASS Investigators
AU - Iversen, Helle Klingenberg
N1 - 2008 Massachusetts Medical Society
PY - 2008/9/25
Y1 - 2008/9/25
N2 - BACKGROUND: Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke.METHODS: After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events.RESULTS: We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alteplase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P=0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P=0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P=0.008). Mortality did not differ significantly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P=0.68). There was no significant difference in the rate of other serious adverse events.CONCLUSIONS: As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.)
AB - BACKGROUND: Intravenous thrombolysis with alteplase is the only approved treatment for acute ischemic stroke, but its efficacy and safety when administered more than 3 hours after the onset of symptoms have not been established. We tested the efficacy and safety of alteplase administered between 3 and 4.5 hours after the onset of a stroke.METHODS: After exclusion of patients with a brain hemorrhage or major infarction, as detected on a computed tomographic scan, we randomly assigned patients with acute ischemic stroke in a 1:1 double-blind fashion to receive treatment with intravenous alteplase (0.9 mg per kilogram of body weight) or placebo. The primary end point was disability at 90 days, dichotomized as a favorable outcome (a score of 0 or 1 on the modified Rankin scale, which has a range of 0 to 6, with 0 indicating no symptoms at all and 6 indicating death) or an unfavorable outcome (a score of 2 to 6 on the modified Rankin scale). The secondary end point was a global outcome analysis of four neurologic and disability scores combined. Safety end points included death, symptomatic intracranial hemorrhage, and other serious adverse events.RESULTS: We enrolled a total of 821 patients in the study and randomly assigned 418 to the alteplase group and 403 to the placebo group. The median time for the administration of alteplase was 3 hours 59 minutes. More patients had a favorable outcome with alteplase than with placebo (52.4% vs. 45.2%; odds ratio, 1.34; 95% confidence interval [CI], 1.02 to 1.76; P=0.04). In the global analysis, the outcome was also improved with alteplase as compared with placebo (odds ratio, 1.28; 95% CI, 1.00 to 1.65; P<0.05). The incidence of intracranial hemorrhage was higher with alteplase than with placebo (for any intracranial hemorrhage, 27.0% vs. 17.6%; P=0.001; for symptomatic intracranial hemorrhage, 2.4% vs. 0.2%; P=0.008). Mortality did not differ significantly between the alteplase and placebo groups (7.7% and 8.4%, respectively; P=0.68). There was no significant difference in the rate of other serious adverse events.CONCLUSIONS: As compared with placebo, intravenous alteplase administered between 3 and 4.5 hours after the onset of symptoms significantly improved clinical outcomes in patients with acute ischemic stroke; alteplase was more frequently associated with symptomatic intracranial hemorrhage. (ClinicalTrials.gov number, NCT00153036.)
KW - Acute Disease
KW - Adult
KW - Aged
KW - Brain Ischemia
KW - Double-Blind Method
KW - Drug Administration Schedule
KW - Female
KW - Fibrinolytic Agents
KW - Humans
KW - Infusions, Intravenous
KW - Intracranial Hemorrhages
KW - Logistic Models
KW - Male
KW - Middle Aged
KW - Odds Ratio
KW - Stroke
KW - Time Factors
KW - Tissue Plasminogen Activator
KW - Treatment Outcome
U2 - 10.1056/NEJMoa0804656
DO - 10.1056/NEJMoa0804656
M3 - Journal article
C2 - 18815396
VL - 359
SP - 1317
EP - 1329
JO - New England Journal of Medicine
JF - New England Journal of Medicine
SN - 0028-4793
IS - 13
ER -
ID: 128983189