Low-Dose versus Standard-Dose Intravenous Alteplase in Acute Ischemic Stroke

• DOI: 10.1056/nejmoa1515510
• Publication Date: 2016-05-10T06:18:17Z
• Authors: Craig S. Anderson; Thompson Robinson; Richard I. Lindley; Hisatomi Arima; Pablo M. Lavados; Tsong-Hai Lee; Joseph P. Broderick; Xiaoying Chen; Guofang Chen; Vijay K. Sharma; Jong S. Kim; Nguyen H. Thang; Yongjun Cao; Mark W. Parsons; Christopher Levi; Yining Huang; Verónica V. Olava...; Andrew M. Demchuk; Philip M. Bath; Geoffrey A. Donnan; Sheila Martins; Octavio M. Pontes...; Federico Silva; Stefano Ricci; Christine Roffe; Jeyaraj Pandian; Laurent Billot; Mark Woodward; Qiang Li; Xia Wang; Jiguang Wang; John Chalmers
• Keywords: Stroke

Thrombolytic therapy for acute ischemic stroke with a lower-than-standard dose of intravenous alteplase may improve recovery along reduced risk intracerebral hemorrhage.Using 2-by-2 quasi-factorial open-label design, we randomly assigned 3310 patients who were eligible thrombolytic (median age, 67 years; 63% Asian) to low-dose (0.6 mg per kilogram body weight) or the standard (0.9 kilogram); underwent randomization within 4.5 hours after onset stroke. The primary objective was determine whether low would be noninferior respect outcome death disability at 90 days, which defined by scores 2 6 on modified Rankin scale (range, 0 [no symptoms] [death]). Secondary objectives superior centrally adjudicated symptomatic hemorrhage and in an ordinal analysis (testing improvement distribution scores). trial included 935 also intensive guideline-recommended blood-pressure control.The occurred 855 1607 participants (53.2%) group 817 1599 (51.1%) standard-dose (odds ratio, 1.09; 95% confidence interval [CI], 0.95 1.25; upper boundary exceeded noninferiority margin 1.14; P=0.51 noninferiority). Low-dose (unadjusted common odds 1.00; CI, 0.89 1.13; P=0.04 Major 1.0% 2.1% (P=0.01); fatal events 7 days 0.5% 1.5%, respectively (P=0.01). Mortality did not differ significantly between two groups (8.5% 10.3%, respectively; P=0.07).This involving predominantly Asian show days. There fewer hemorrhages alteplase. (Funded National Health Medical Research Council Australia others; ENCHANTED ClinicalTrials.gov number, NCT01422616.).