Effects of Ultraearly Intravenous Thrombolysis on Outcomes in Ischemic Stroke
Authors: Alexander Kunz, Christian H. Nolte, Hebun Erdur, Jochen B. Fiebach, Frederik Geisler, Michal Rozanski, Jan F. Scheitz, Kersten Villringer, Carolin Waldschmidt, Joachim E. Weber, Matthias Wendt, Benjamin Winter, Katja Zieschang, Ulrike Grittner, Sabina Kaczmarek, Matthias Endres, Martin Ebinger, Heinrich J. Audebert
Journal: Circulation (2017)

T he effects of intravenous thrombolysis (IVT) in ischemic stroke are time dependent. 1,2Because of delays in conventional stroke workup, previous randomized IVT trials were unable to include patients with onset-to-treatment time (OTT) ≤60 minutes of symptom onset.With the invention of computed tomography-equipped mobile stroke units (MSUs), a relevant proportion of patients treated on such ambulances receive IVT within this ultraearly time window. 3In this study, we assessed the effects of IVT on 3-month functional outcome and mortality in different OTT intervals, including the first hour after onset, using a pooled analysis of 2 prospective prehospital and in-hospital registries in Berlin/Germany. 4ethods of patient inclusion and documentation in the 2 registries were described elsewhere 4 (URL: http://www.clinicaltrials.gov.Unique identifier: NCT02358772).Briefly, all patients admitted through emergency medical services who received IVT between February 5, 2011, and March 5, 2015, were included in the registries.The prehospital registry included patients thrombolysed in an MSU and admitted to the nearest stroke unit thereafter.Intra-arterial treatment was optional in patients with occlusion of proximal intracranial arteries in both cohorts.The in-hospital registry comprised patients receiving IVT at Charité-Universitätsmedizin, Campus Benjamin Franklin.We excluded patients with nonstroke diagnosis, IVT without known exact (witnessed) time of onset, denial/withdrawal of informed consent for follow-up, missing 3-month follow-up, or incomplete documentation of data used in the multivariable analyses.For the pooled analyses of time-to-treatment effects, we included all ischemic stroke patients who received IVT within 4.5 hours.We compared results of the first two 60-minute OTT intervals with OTT of 121 to 270 minutes as reference.The primary outcome was survival without disability (modified Rankin Scale [mRS] score ≤1 at 3 months after ischemic stroke).The primary study population did not include patients who had previously lived with need of assistance because only patients without prestroke disability can realistically achieve an outcome of mRS score ≤1.Secondary outcomes were survival without severe disability (mRS score ≤3) and mortality at 3 months (also assessed in the entire study population, including patients with prestroke need of assistance).These outcomes were assessed by certified mRS raters through standardized telephone interview or based on information from Berlin registration offices.Outcomes were adjusted in multivariable regression for demographics, comorbidities, intra-arterial treatment, and stroke severity according to the National Institutes of Health Stroke Scale as a continuous variable (Table ).Because of the low 3-month mortality, we had to restrict the covariables in this regression analysis to age, continuous National Institutes of Health Stroke Scale, and time intervals.A 2-sided significance level of α=0.05 was applied with IBM SPSS Statistics version 22.