Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke

被引:5161
作者
Hacke, Werner [1 ]
Kaste, Markku [2 ]
Bluhmki, Erich [3 ]
Brozman, Miroslav [4 ]
Davalos, Antoni [5 ]
Guidetti, Donata [6 ]
Larrue, Vincent [7 ]
Lees, Kennedy R. [8 ]
Medeghri, Zakaria
Machnig, Thomas [9 ]
Schneider, Dietmar [10 ]
von Kummer, Ruediger [11 ]
Wahlgren, Nils [12 ]
Toni, Danilo [13 ]
机构
[1] Heidelberg Univ, Dept Neurol, D-69120 Heidelberg, Germany
[2] Univ Helsinki, Cent Hosp, Dept Neurol, Helsinki, Finland
[3] Boehringer Ingelheim KG, Dept Stat, Biberach, Germany
[4] Univ Hosp Nitra, Neurol Clin, Nitra, Slovakia
[5] Hosp Badalona Germans Trias & Pujol, Dept Neurosci, Barcelona, Spain
[6] Hosp Piacenza, Dept Neurol, Piacenza, Italy
[7] Univ Toulouse 1, Dept Neurol, F-31042 Toulouse, France
[8] Univ Glasgow, Fac Med, Glasgow, Lanark, Scotland
[9] Boehringer Ingelheim Pharmaceut Inc, Reims, France
[10] Univ Leipzig, Dept Neurol, Leipzig, Germany
[11] Tech Univ Dresden, Dept Neuroradiol, Dresden, Germany
[12] Karolinska Inst, Dept Neurol, Stockholm, Sweden
[13] Univ Roma La Sapienza, Dept Neurol Sci, Rome, Italy
关键词
D O I
10.1056/NEJMoa0804656
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.).
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收藏
页码:1317 / 1329
页数:13
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