title: Meta-analysis of clinical outcomes of intravenous recombinant tissue plasminogen activator for acute ischemic stroke: within 3 hours versus 3-4.5 hours.
abstract: OBJECTIVE
  This meta-analysis was to compare clinical outcomes of intravenous recombinant tissue plasminogen activator (IV rtPA) administered within 3 hours versus 3-4.5 hours after symptom onset.
  
  
  METHODS
  We collected all interventional or observational studies that compared clinical outcomes of IV rtPA treatment within 3 hours and 3-4.5 hours after acute ischemic stroke onset by searching PubMed (up to October 2012), Embase (1966 to October 2012) and Web of Science (2003 to October 2012) as well as manually searching the references of articles retrieved. The combined effect was calculated by odds ratios (ORs) and 95% confidence intervals (CIs) to analyze favorable functional outcome, mortality and symptomatic intracranial hemorrhage (sICH) at 90 days. Publication bias was analyzed by Begg's funnel plot and Egger's regression test.
  
  
  RESULTS
  Our initial search identified a total of 27,391 articles. After reviewing the titles, abstracts and full text, a total of six studies and more than 25,000 patients were included in the final meta-analysis. The combined analyses demonstrated significant differences in the favorable outcome (modified Rankin scale, mRS: 0-2): OR = 0.89, 95% CI = 0.81-0.98 and very favorable outcomes (mRS: 0-1): OR = 0.86, 95% CI = 0.78-0.94 between two groups, which were both in favor of the 3-4.5 hours group. When all studies reporting data on sICH were combined, the overall summary OR indicated no differences in the two groups. The combined analyses showed no significant differences in 90 day mortality and 7 day mortality between within 3 hours and 3-4.5 hours.
  
  
  CONCLUSIONS
  This meta-analysis does not provide any evidence that treatment with rtPA within 3-4.5 hours is less safe than treatment within 3 hours. It suggests that treatment with IV rtPA may be recommended to ischemic stroke patients that present within 4.5 hours of onset, although every effort should be made to give those patients IV rtPA within 3 hours of symptom onset.
authors.affiliation: Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Bing-Hu
authors.initials: BH
authors.lastname: Li
authors.forename: Xin
authors.initials: X
authors.lastname: Ding
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Yin
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Chang-Yue
authors.initials: CY
authors.lastname: Gao
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhang
authors.forename: Jing-Cheng
authors.initials: JC
authors.lastname: Li
mesh_terms: D000208:Acute Disease; D061605:Administration, Intravenous; D002545:Brain Ischemia / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D010960:Plasminogen Activators / Q000008:administration & dosage*; D039781:PubMed; D011994:Recombinant Proteins / Q000008:administration & dosage; D012044:Regression Analysis; D020521:Stroke / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D013997:Time Factors
chemical_list: D011994:Recombinant Proteins; D010960:Plasminogen Activators