title: Results of intravenous thrombolysis within 4.5 to 6 hours and updated results within 3 to 4.5 hours of onset of acute ischemic stroke recorded in the Safe Implementation of Treatment in Stroke International Stroke Thrombolysis Register (SITS-ISTR): an observational study.
abstract: OBJECTIVE
  Pooled analysis of randomized controlled trials of intravenous thrombolysis shows no statistically significant benefit beyond 4.5 hours, with the possible advantage perhaps offset by risk.
  
  
  OBJECTIVE
  To compare the outcomes of patients who were treated within 4.5 to 6 hours or within 3 to 4.5 hours of the onset of an ischemic stroke with the outcomes of patients who were treated within 3 hours in the SITS-ISTR.
  
  
  METHODS
  An observational study based on SITS-ISTR data during the period from 2002 to 2011.
  
  
  METHODS
  Acute and emergency care.
  
  
  METHODS
  Of 29 618 patients with acute ischemic stroke, 283 (1.0%) were treated within 4.5 to 6 hours of onset, 4056 (13.7%) were within 3 to 4.5 hours of onset, and 25 279 (85.4%) were treated within 3 hours of onset, in compliance with other European Union approval criteria.
  
  
  METHODS
  Intravenous thrombolysis with alteplase.
  
  
  METHODS
  Functional independence (modified Rankin Scale score of 0-2) and mortality at 3 months and symptomatic intracerebral hemorrhage (SICH). P values are based on comparisons between patients treated within 4.5 to 6 hours or within 3 to 4.5 hours of onset against patients treated within 3 hours of onset.
  
  
  RESULTS
  Results are presented as within 4.5 to 6 hour vs within 3 to 4.5 hours vs within 3 hours. Median time from stroke onset to treatment was 295 vs 210 minutes vs 138 minutes (P < .01), median age was 65 vs 67 vs 68 years (P < .01), and median baseline National Institutes of Health Stroke Scale score was 9 vs 9 vs 12 (P < .01). Rate of functional independence was 61.3% (P = .40) vs 62.7% (P < .01) vs 58.4%; mortality rate was 11.8% (P = .99) vs 11.1% (P = .21) vs 11.8%; and rate of SICH was 2.6% (P = .17) vs 1.8% (P = .27) vs 1.5%. Multivariate analysis detected no significant difference in SICH (P > .05), mortality (P > .05), or independence (P > .05). Time from stroke onset to treatment as a continuous variable was significantly associated with higher rates of SICH and poor 3-month outcome after adjustment for age and National Institutes of Health Stroke Scale score.
  
  
  CONCLUSIONS
  The treatment remains safe and effective for patients treated within 3 to 4.5 hours compared with patients treated within 3 hours. Our selected group of patients treated within 4.5 to 6 hours of stroke onset did not have worse outcomes than patients treated within 3 hours. An inevitable limitation of our observational study is the possible nonequivalence of the cohorts, particularly the 4.5- to 6-hour cohort relative to the other 2 cohorts.
authors.affiliation: Department of Clinical Neurosciences, Karolinska Institutet. niaz.ahmed@karolinska.se
authors.forename: Niaz
authors.initials: N
authors.lastname: Ahmed
authors.forename: Lars
authors.initials: L
authors.lastname: Kellert
authors.forename: Kennedy R
authors.initials: KR
authors.lastname: Lees
authors.forename: Robert
authors.initials: R
authors.lastname: Mikulik
authors.forename: Turgut
authors.initials: T
authors.lastname: Tatlisumak
authors.forename: Danilo
authors.initials: D
authors.lastname: Toni
mesh_terms: D000208:Acute Disease; D000368:Aged; D002545:Brain Ischemia / Q000188:drug therapy* / Q000401:mortality; D002985:Clinical Protocols / Q000592:standards*; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D012042:Registries; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality; D015912:Thrombolytic Therapy / Q000379:methods* / Q000592:standards; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator