title: Impact of Computed Tomography Perfusion Imaging on the Response to Tenecteplase in Ischemic Stroke: Analysis of 2 Randomized Controlled Trials.
abstract: BACKGROUND
  We pooled 2 clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of tenecteplase and the other that showed no difference between the treatments in patient clinical outcomes. We tested the hypotheses that reperfusion therapy with tenecteplase would be superior to alteplase in improving functional outcomes in the group of patients with target mismatch as identified with advanced imaging.
  
  
  METHODS
  We investigated whether tenecteplase-treated patients had a different 24-hour reduction in the National Institutes of Health Stroke Scale and a favorable odds ratio of a modified Rankin scale score of 0 to 1 versus 2 to 6 compared with alteplase-treated patients using linear regression to generate odds ratios. Imaging outcomes included rates of vessel recanalization and infarct growth at 24 hours and occurrence of large parenchymal hematoma. Baseline computed tomography perfusion was analyzed to assess whether patients met the target mismatch criteria (absolute mismatch volume >15 mL, mismatch ratio >1.8, baseline ischemic core <70 mL, and volume of severely hypoperfused tissue <100 mL). Patients meeting target mismatch criteria were analyzed as a subgroup to identify whether they had different treatment responses from the pooled group.
  
  
  RESULTS
  Of 146 pooled patients, 71 received alteplase and 75 received tenecteplase. Tenecteplase-treated patients had greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 7; alteplase, 2; P=0.018) and less parenchymal hematoma (2 of 75 versus 10 of 71; P=0.02). The pooled group did not show improved patient outcomes when treated with tenecteplase (modified Rankin scale score 0-1: odds ratio, 1.77; 95% confidence interval, 0.89-3.51; P=0.102) compared with alteplase therapy. However, in patients with target mismatch (33 tenecteplase, 35 alteplase), treatment with tenecteplase was associated with greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 6; alteplase, 1; P<0.001) and better late independent recovery (modified Rankin scale score 0-1: odds ratio, 2.33; 95% confidence interval, 1.13-5.94; P=0.032) than those treated with alteplase.
  
  
  CONCLUSIONS
  Tenecteplase may offer an improved efficacy and safety profile compared with alteplase, benefits possibly exaggerated in patients with baseline computed tomography perfusion-defined target mismatch.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926. URL: https://www.anzctr.org.au. Unique identifier: ACTRN12608000466347.
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.). andrew.bivard@hotmail.com.
authors.forename: Andrew
authors.initials: A
authors.lastname: Bivard
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Xuya
authors.initials: X
authors.lastname: Huang
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Patrick
authors.initials: P
authors.lastname: McElduff
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Levi
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Bruce C V
authors.initials: BC
authors.lastname: Campbell
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Bharath Kumar
authors.initials: BK
authors.lastname: Cheripelli
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Kalladka
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Fiona Catherine
authors.initials: FC
authors.lastname: Moreton
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Ian
authors.initials: I
authors.lastname: Ford
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Bladin
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Davis
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Donnan
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Keith W
authors.initials: KW
authors.lastname: Muir
authors.affiliation: From Department of Neurology, John Hunter Hospital, University of Newcastle, Australia (A.B., P.M., C.R.L., M.W.D.); Institute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Scotland, UK (X.H., B.K.C., D.K., F.C.M., I.F., K.W.M.); Department of Medicine and Neurology, Royal Melbourne Hospital (B.C.V.C., S.M.D.), and The Florey Institute of Neuroscience and Mental Health (C.F.B., G.A.D.), University of Melbourne, Australia; and Department of Neurology, Eastern Health Clinical School, Monash University, Melbourne, Australia (C.F.B.).
authors.forename: Mark W
authors.initials: MW
authors.lastname: Parsons
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D055420:Perfusion Imaging / Q000379:methods*; D015424:Reperfusion / Q000379:methods*; D020521:Stroke / Q000000981:diagnostic imaging / Q000188:drug therapy*; D000077785:Tenecteplase; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D010959:Tissue Plasminogen Activator; D000077785:Tenecteplase
keywords: perfusion imaging; stroke, ischemic; thrombolytic therapy