Thrombolysis with alteplase 3 to 4.5 hours after acute ischemic stroke
Werner Hacke, Markku Kaste, Erich Bluhmki, Miroslav Brozman, Antoni Dávalos, Donata Guidetti, Vincent Larrue, Kennedy R Lees, Zakaria Medeghri, Thomas Machnig, Dietmar Schneider, Rüdiger von Kummer, Nils Wahlgren, Danilo Toni, ECASS Investigators, W Hacke, A Dávalos, M Kaste, R von Kummer, V Larrue, D Toni, N Wahlgren, K R Lees, W D Heiss, E Lesaffre, J M Orgogozo, R von Kummer, S Bastianello, J M Wardlaw, J-C Peyrieux, C Sauce, Z Medeghri, R Mazenc, C Sauce, T Machnig, E Bluhmki, F Aichner, C Alf, U Baumhackl, M Brainin, C Eggers, F Gruber, G Ladurner, K Niederkorn, G Noistering, J Willeit, G Vanhooren, S Blecic, B Bruneel, J Caekebeke, P Laloux, P J Simons, V Thijs, M Bar, H Dvorakova, D Vaclavik, G Boysen, G Andersen, H K Iversen, B Traberg-Kristensen, M Kaste, R Marttila, J Sivenius, P Trouillas, P Amarenco, J Bouillat, X Ducrocq, M Giroud, A Jaillard, J-M Larrieu, V Larrue, D Leys, C Magne, M-H Mahagne, D Milhaud, D Sablot, D Saudeau, O Busse, J Berrouschot, J H Faiss, J Glahn, M Görtler, A Grau, M Grond, R Haberl, G Hamann, M Hennerici, H Koch, P Krauseneck, J Marx, S Meves, U Meyding-Lamadé, P Ringleb, D Schneider, A Schwarz, J Sobesky, P Urban, K Karageorgiou, A Komnos, A Csányi, L Csiba, A Valikovics, D Toni, G Agnelli, G Billo, P Bovi, G Comi, G Gigli, D Guidetti, D Inzitari, N Marcello, C Marini, G Orlandi, M Pratesi, M Rasura, A Semplicini, C Serrati, T Tassinari, P J A M Brouwers, J Stam, H Naess, B Indredavik, R Kloster, A Czlonkowska, A Kuczyńska-Zardzewialy, W Nyka, G Opala, S Romanowicz, L Cunha, C Correia, V Cruz, T Pinho e Melo, M Brozman, M Dvorak, R Garay, G Krastev, E Kurca, J Alvarez-Sabin, A Chamorro, M del Mar Freijo Guerrero, J A E Herrero, A Gil-Peralta, R Leira, J L Martí-Vilalta, J Masjuan Vallejo, M Millán, C Molina, E Mostacero, T Segura, J Serena, J Vivancos Mora, E Danielsson, B Cederin, von Zweigberg, N-G Wahlgren, L Welin, P Lyrer, J Bogousslavsky, H-J Hungerbühler, B Weder, G A Ford, D Jenkinson, M J MacLeod, R S MacWalter, H S Markus, K W Muir, A K Sharma, M R Walters, E A Warburton, Werner Hacke, Markku Kaste, Erich Bluhmki, Miroslav Brozman, Antoni Dávalos, Donata Guidetti, Vincent Larrue, Kennedy R Lees, Zakaria Medeghri, Thomas Machnig, Dietmar Schneider, Rüdiger von Kummer, Nils Wahlgren, Danilo Toni, ECASS Investigators, W Hacke, A Dávalos, M Kaste, R von Kummer, V Larrue, D Toni, N Wahlgren, K R Lees, W D Heiss, E Lesaffre, J M Orgogozo, R von Kummer, S Bastianello, J M Wardlaw, J-C Peyrieux, C Sauce, Z Medeghri, R Mazenc, C Sauce, T Machnig, E Bluhmki, F Aichner, C Alf, U Baumhackl, M Brainin, C Eggers, F Gruber, G Ladurner, K Niederkorn, G Noistering, J Willeit, G Vanhooren, S Blecic, B Bruneel, J Caekebeke, P Laloux, P J Simons, V Thijs, M Bar, H Dvorakova, D Vaclavik, G Boysen, G Andersen, H K Iversen, B Traberg-Kristensen, M Kaste, R Marttila, J Sivenius, P Trouillas, P Amarenco, J Bouillat, X Ducrocq, M Giroud, A Jaillard, J-M Larrieu, V Larrue, D Leys, C Magne, M-H Mahagne, D Milhaud, D Sablot, D Saudeau, O Busse, J Berrouschot, J H Faiss, J Glahn, M Görtler, A Grau, M Grond, R Haberl, G Hamann, M Hennerici, H Koch, P Krauseneck, J Marx, S Meves, U Meyding-Lamadé, P Ringleb, D Schneider, A Schwarz, J Sobesky, P Urban, K Karageorgiou, A Komnos, A Csányi, L Csiba, A Valikovics, D Toni, G Agnelli, G Billo, P Bovi, G Comi, G Gigli, D Guidetti, D Inzitari, N Marcello, C Marini, G Orlandi, M Pratesi, M Rasura, A Semplicini, C Serrati, T Tassinari, P J A M Brouwers, J Stam, H Naess, B Indredavik, R Kloster, A Czlonkowska, A Kuczyńska-Zardzewialy, W Nyka, G Opala, S Romanowicz, L Cunha, C Correia, V Cruz, T Pinho e Melo, M Brozman, M Dvorak, R Garay, G Krastev, E Kurca, J Alvarez-Sabin, A Chamorro, M del Mar Freijo Guerrero, J A E Herrero, A Gil-Peralta, R Leira, J L Martí-Vilalta, J Masjuan Vallejo, M Millán, C Molina, E Mostacero, T Segura, J Serena, J Vivancos Mora, E Danielsson, B Cederin, von Zweigberg, N-G Wahlgren, L Welin, P Lyrer, J Bogousslavsky, H-J Hungerbühler, B Weder, G A Ford, D Jenkinson, M J MacLeod, R S MacWalter, H S Markus, K W Muir, A K Sharma, M R Walters, E A Warburton
Abstract
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.)
2008 Massachusetts Medical Society
Source: PubMed