title: Tenecteplase versus alteplase in stroke thrombolysis: An individual patient data meta-analysis of randomized controlled trials.
abstract: Tenecteplase, a modified plasminogen activator with higher fibrin specificity and longer half-life, may have advantages over alteplase in acute ischemic stroke thrombolysis.
  
  
  
  We undertook an individual patient data meta-analysis of randomized controlled trials that compared alteplase with tenecteplase in acute stroke.
  
  
  
  Eligible studies were identified by a MEDLINE search, and individual patient data were acquired. We compared clinical outcomes including modified Rankin Scale at three months, early neurological improvement at 24 h, intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and mortality at three months between all dose tiers of tenecteplase and alteplase.
  
  
  
  Three relevant studies (Haley et al., Parsons et al., and ATTEST) included 291 patients and investigated three doses of tenecteplase (0.1, 0.25, 0.4 mg/kg). There were no differences between any dose of tenecteplase and alteplase for either efficacy or safety end points. Tenecteplase 0.25 mg/kg had the greatest odds to achieve early neurological improvement (OR [95%CI] 3.3 [1.5, 7.2], p = 0.093), excellent functional outcome (modified Rankin Scale 0-1) at three months (OR [95%CI] 1.9 [0.8, 4.4], p = 0.28), with reduced odds of intracerebral hemorrhage (OR [95%CI] 0.6 [0.2, 1.8], P = 0.43) compared with alteplase. Only 19 patients were treated with tenecteplase 0.4 mg/kg, which showed increased odds of symptomatic intracerebral hemorrhage compared with alteplase (OR [95% CI] 6.2 [0.7, 56.3]).
  
  
  
  While no significant differences between tenecteplase and alteplase were found, point estimates suggest potentially greater efficacy of 0.25 and 0.1 mg/kg doses with no difference in symptomatic intracerebral hemorrhage, and potentially higher symptomatic intracerebral hemorrhage risk with the 0.4 mg/kg dose. Further investigation of 0.25 mg/kg tenecteplase is warranted.
authors.affiliation: Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.
authors.forename: Xuya
authors.initials: X
authors.lastname: Huang
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Rachael
authors.initials: R
authors.lastname: MacIsaac
authors.affiliation: Department of Biostatistics, Columbia University, New York, USA.
authors.forename: John Lp
authors.initials: JL
authors.lastname: Thompson
authors.affiliation: Department of Biostatistics, Columbia University, New York, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Levin
authors.affiliation: Department of Biostatistics, Columbia University, New York, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Buchsbaum
authors.affiliation: Department of Neurology, University of Virginia, Charlottesville, USA.
authors.forename: E Clarke
authors.initials: EC
authors.lastname: Haley
authors.affiliation: Department of Neurology, University of Newcastle, Newcastle, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Levi
authors.affiliation: Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia.
authors.forename: Bruce
authors.initials: B
authors.lastname: Campbell
authors.affiliation: The Department of Neurosciences, Monash University, Melbourne, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bladin
authors.affiliation: Department of Neurology, University of Newcastle, Newcastle, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Parsons
authors.affiliation: Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK keith.muir@glasgow.ac.uk.
authors.forename: Keith W
authors.initials: KW
authors.lastname: Muir
mesh_terms: D000368:Aged; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000188:drug therapy*; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: Acute stroke therapy; alteplase; intracerebral hemorrhage; meta-analysis; tenecteplase; thrombolysis