title: Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials.
abstract: BACKGROUND
  Quick administration of intravenous recombinant tissue plasminogen activator (rt-PA) after stroke improved outcomes in previous trials. We aimed to analyse combined data for individual patients to confirm the importance of rapid treatment.
  
  
  METHODS
  We pooled common data elements from six randomised placebo-controlled trials of intravenous rt-PA. Using multivariable logistic regression we assessed the relation of the interval from stroke onset to start of treatment (OTT) on favourable 3-month outcome and on the occurrence of clinically relevant parenchymal haemorrhage.
  
  
  RESULTS
  Treatment was started within 360 min of onset of stroke in 2775 patients randomly allocated to rt-PA or placebo. Median age was 68 years, median baseline National Institute of Health Stroke Scale (NIHSS) 11, and median OTT 243 min. Odds of a favourable 3-month outcome increased as OTT decreased (p=0.005). Odds were 2.8 (95% CI 1.8-4.5) for 0-90 min, 1.6 (1.1-2.2) for 91-180 min, 1.4 (1.1-1.9) for 181-270 min, and 1.2 (0.9-1.5) for 271-360 min in favour of the rt-PA group. The hazard ratio for death adjusted for baseline NIHSS was not different from 1.0 for the 0-90, 91-180, and 181-270 min intervals; for 271-360 min it was 1.45 (1.02-2.07). Haemorrhage was seen in 82 (5.9%) rt-PA patients and 15 (1.1%) controls (p<0.0001). Haemorrhage was not associated with OTT but was with rt-PA treatment (p=0.0001) and age (p=0.0002).
  
  
  CONCLUSIONS
  The sooner that rt-PA is given to stroke patients, the greater the benefit, especially if started within 90 min. Our results suggest a potential benefit beyond 3 h, but this potential might come with some risks.
authors.affiliation: Medical University at Heidelberg, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Hacke
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Donnan
authors.forename: Cesare
authors.initials: C
authors.lastname: Fieschi
authors.forename: Markku
authors.initials: M
authors.lastname: Kaste
authors.forename: Rüdiger
authors.initials: R
authors.lastname: von Kummer
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
authors.forename: Thomas
authors.initials: T
authors.lastname: Brott
authors.forename: Michael
authors.initials: M
authors.lastname: Frankel
authors.forename: James C
authors.initials: JC
authors.lastname: Grotta
authors.forename: E Clarke
authors.initials: EC
authors.lastname: Haley
authors.forename: Thomas
authors.initials: T
authors.lastname: Kwiatkowski
authors.forename: Steven R
authors.initials: SR
authors.lastname: Levine
authors.forename: Chris
authors.initials: C
authors.lastname: Lewandowski
authors.forename: Mei
authors.initials: M
authors.lastname: Lu
authors.forename: Patrick
authors.initials: P
authors.lastname: Lyden
authors.forename: John R
authors.initials: JR
authors.lastname: Marler
authors.forename: Suresh
authors.initials: S
authors.lastname: Patel
authors.forename: Barbara C
authors.initials: BC
authors.lastname: Tilley
authors.forename: Gregory
authors.initials: G
authors.lastname: Albers
authors.forename: Erich
authors.initials: E
authors.lastname: Bluhmki
authors.forename: Manfred
authors.initials: M
authors.lastname: Wilhelm
authors.forename: Scott
authors.initials: S
authors.lastname: Hamilton
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator