title: Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke.
abstract: OBJECTIVE
  Randomized clinical trials suggest the benefit of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke is time dependent. However, modest sample sizes have limited characterization of the extent to which onset to treatment (OTT) time influences outcome; and the generalizability of findings to clinical practice is uncertain.
  
  
  OBJECTIVE
  To evaluate the degree to which OTT time is associated with outcome among patients with acute ischemic stroke treated with intraveneous tPA.
  
  
  METHODS
  Data were analyzed from 58,353 patients with acute ischemic stroke treated with tPA within 4.5 hours of symptom onset in 1395 hospitals participating in the Get With The Guidelines-Stroke Program, April 2003 to March 2012.
  
  
  METHODS
  Relationship between OTT time and in-hospital mortality, symptomatic intracranial hemorrhage, ambulatory status at discharge, and discharge destination.
  
  
  RESULTS
  Among the 58,353 tPA-treated patients, median age was 72 years, 50.3% were women, median OTT time was 144 minutes (interquartile range, 115-170), 9.3% (5404) had OTT time of 0 to 90 minutes, 77.2% (45,029) had OTT time of 91 to 180 minutes, and 13.6% (7920) had OTT time of 181 to 270 minutes. Median pretreatment National Institutes of Health Stroke Scale documented in 87.7% of patients was 11 (interquartile range, 6-17). Patient factors most strongly associated with shorter OTT included greater stroke severity (odds ratio [OR], 2.8; 95% CI, 2.5-3.1 per 5-point increase), arrival by ambulance (OR, 5.9; 95% CI, 4.5-7.3), and arrival during regular hours (OR, 4.6; 95% CI, 3.8-5.4). Overall, there were 5142 (8.8%) in-hospital deaths, 2873 (4.9%) patients had intracranial hemorrhage, 19,491 (33.4%) patients achieved independent ambulation at hospital discharge, and 22,541 (38.6%) patients were discharged to home. Faster OTT, in 15-minute increments, was associated with reduced in-hospital mortality (OR, 0.96; 95% CI, 0.95-0.98; P < .001), reduced symptomatic intracranial hemorrhage (OR, 0.96; 95% CI, 0.95-0.98; P < .001), increased achievement of independent ambulation at discharge (OR, 1.04; 95% CI, 1.03-1.05; P < .001), and increased discharge to home (OR, 1.03; 95% CI, 1.02-1.04; P < .001).
  
  
  CONCLUSIONS
  In a registry representing US clinical practice, earlier thrombolytic treatment was associated with reduced mortality and symptomatic intracranial hemorrhage, and higher rates of independent ambulation at discharge and discharge to home following acute ischemic stroke. These findings support intensive efforts to accelerate hospital presentation and thrombolytic treatment in patients with stroke.
authors.affiliation: Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA. jsaver@mednet.ucla.edu
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Saver
authors.forename: Gregg C
authors.initials: GC
authors.lastname: Fonarow
authors.forename: Eric E
authors.initials: EE
authors.lastname: Smith
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Reeves
authors.forename: Maria V
authors.initials: MV
authors.lastname: Grau-Sepulveda
authors.forename: Wenqin
authors.initials: W
authors.lastname: Pan
authors.forename: Daiwai M
authors.initials: DM
authors.lastname: Olson
authors.forename: Adrian F
authors.initials: AF
authors.lastname: Hernandez
authors.forename: Eric D
authors.initials: ED
authors.lastname: Peterson
authors.forename: Lee H
authors.initials: LH
authors.lastname: Schwamm
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006304:Health Status; D017052:Hospital Mortality; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D010351:Patient Discharge / Q000706:statistics & numerical data; D012042:Registries; D012189:Retrospective Studies; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator