Journal ArticleDOI
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 +13 more
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TLDR
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.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 alte plase 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 significant ly 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.)read more
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Predictors and clinical relevance of hemorrhagic transformation after endovascular therapy for anterior circulation large vessel occlusion strokes: a multicenter retrospective analysis of 1122 patients
Raul G. Nogueira,Rishi Gupta,Tudor G Jovin,Elad I. Levy,David S Liebeskind,Osama O. Zaidat,Ansaar T Rai,Joshua A Hirsch,Daniel P Hsu,Marilyn M. Rymer,Ashis H Tayal,Ridwan Lin,Sabareesh K. Natarajan,Ashish Nanda,Melissa Tian,Qing Hao,Junaid S. Kalia,Michael Chen,Alex Abou-Chebl,Thanh N. Nguyen,Albert J Yoo +20 more
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Association between brain imaging signs, early and late outcomes, and response to intravenous alteplase after acute ischaemic stroke in the third international stroke trial (IST-3): Secondary analysis of a randomised controlled trial
Joanna M. Wardlaw,Peter Sandercock,Geoff Cohen,Andrew J. Farrall,Richard I. Lindley,Richard I. Lindley,Rudiger von Kummer,Rudiger von Kummer,Anders von Heijne,Nick Bradey,Nick Bradey,André Peeters,Lesley Cala,Lesley Cala,Alessandro Adami,Alessandro Adami,Zoe Morris,Gillian Potter,Gordon Murray,William Whiteley,David J. Perry,Eleni Sakka +21 more
TL;DR: Some early ischaemic and pre-existing signs were associated with reduced independence at 6 months and increased symptomatic intracranial haemorrhage after alteplase, and some combinations of signs increased some absolute risks.
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Efficacy of Intra-Arterial Fibrinolysis for Acute Ischemic Stroke Meta-Analysis of Randomized Controlled Trials
TL;DR: Formal meta-analysis suggests that IA fibrinolysis substantially increases recanalization rates and good and excellent clinical outcomes in acute ischemic stroke.
Journal ArticleDOI
Pretreatment diffusion and perfusion MR lesion volumes have a crucial influence on clinical response to stroke thrombolysis
Mark W Parsons,Soren Christensen,Patrick McElduff,Christopher R Levi,Kenneth Butcher,Deidre A De Silva,Martin Ebinger,P. Alan Barber,Christopher F. Bladin,Geoffrey A. Donnan,Stephen M. Davis +10 more
TL;DR: Clinical responsiveness to IV-tPA, and stroke outcome, depends more on baseline DWI and PWI lesion volumes than the extent of perfusion–diffusion mismatch.
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New approaches to neuroprotective drug development.
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References
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Measurements of acute cerebral infarction: a clinical examination scale.
Thomas Brott,Harold P. Adams,Charles P. Olinger,John R. Marler,William G. Barsan,José Biller,Judith Spilker,R Holleran,Robert Eberle,Vicki S. Hertzberg +9 more
TL;DR: A 15-item neurologic examination stroke scale for use in acute stroke therapy trials was designed and interrater reliability for the scale was found to be high, and test-retest reliability was also high, suggesting acceptable examination and scale validity.
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