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March 06, 2023Research Article

Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post-Hoc Analysis of the EXTEND-IA TNK Trials

View ORCID ProfileVignan Yogendrakumar, Leonid Churilov, Peter J Mitchell, Timothy J Kleinig, View ORCID ProfileNawaf Yassi, View ORCID ProfileVincent Thijs, Teddy Wu, Darshan Shah, Peter Bailey, View ORCID ProfileHelen M Dewey, Philip MC Choi, Alice Ma, View ORCID ProfileTissa Wijeratne, View ORCID ProfileCarlos Garcia-Esperon, View ORCID ProfileGeoffrey Cloud, Ronil V. Chandra, Dennis John Cordato, Bernard Yan DMedSc, Gagan Sharma, Patricia M Desmond, Mark W Parsons, Geoffrey Alan Donnan, Stephen M Davis, View ORCID ProfileBruce C. V. Campbell
First published March 6, 2023, DOI: https://doi.org/10.1212/WNL.0000000000207138
Vignan Yogendrakumar
1Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, Australia
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  • ORCID record for Vignan Yogendrakumar
  • For correspondence: vyogendrakum@student.unimelb.edu.au
Leonid Churilov
1Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, Australia
2Melbourne Medical School, University of Melbourne, Heidelberg, Australia
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Peter J Mitchell
3Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia
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Timothy J Kleinig
4Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia
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Nawaf Yassi
1Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, Australia
5Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Australia
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  • ORCID record for Nawaf Yassi
Vincent Thijs
2Melbourne Medical School, University of Melbourne, Heidelberg, Australia
6Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Australia
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Teddy Wu
7Department of Neurology, Christchurch Hospital, Christchurch, New Zealand
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Darshan Shah
8Department of Neurology, Princess Alexandra Hospital, Brisbane, Queensland, Australia
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Peter Bailey
9Department of Neurology, Gold Coast University Hospital, Queensland, Australia
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Helen M Dewey
10Eastern Health and Eastern Health Clinical School, Department of Neurosciences, Monash University, Clayton, Victoria, Australia
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  • ORCID record for Helen M Dewey
Philip MC Choi
10Eastern Health and Eastern Health Clinical School, Department of Neurosciences, Monash University, Clayton, Victoria, Australia
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Alice Ma
11Royal North Shore Hospital, New South Wales, Australia
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Tissa Wijeratne
12Melbourne Medical School, Department of Medicine and Neurology, The University of Melbourne and Western Health, Sunshine Hospital, St Albans Victoria, Australia
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Carlos Garcia-Esperon
13Department of Neurology, John Hunter Hospital, Newcastle, New South Wales, Australia
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Geoffrey Cloud
14Department of Neurology, Alfred Hospital, Melbourne, Australia
15Department of Neuroscience, Central Clinical School, Monash University, Melbourne
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Ronil V. Chandra
16NeuroInterventional Radiology Unit, Monash Health, Monash University, Australia
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Dennis John Cordato
17Department of Neurology, Liverpool Hospital, University of New South Wales, Sydney, Australia
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Bernard Yan DMedSc
1Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, Australia
4Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia
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Gagan Sharma
1Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, Australia
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Patricia M Desmond
4Department of Neurology, Royal Adelaide Hospital, Adelaide, Australia
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Mark W Parsons
1Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, Australia
17Department of Neurology, Liverpool Hospital, University of New South Wales, Sydney, Australia
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Geoffrey Alan Donnan
1Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, Australia
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Stephen M Davis
1Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, Australia
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Bruce C. V. Campbell
1Department of Medicine and Neurology, Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville, Australia
3Department of Radiology, Royal Melbourne Hospital, University of Melbourne, Parkville, Australia
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  • ORCID record for Bruce C. V. Campbell
Full PDF
Citation
Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post-Hoc Analysis of the EXTEND-IA TNK Trials
Vignan Yogendrakumar, Leonid Churilov, Peter J Mitchell, Timothy J Kleinig, Nawaf Yassi, Vincent Thijs, Teddy Wu, Darshan Shah, Peter Bailey, Helen M Dewey, Philip MC Choi, Alice Ma, Tissa Wijeratne, Carlos Garcia-Esperon, Geoffrey Cloud, Ronil V. Chandra, Dennis John Cordato, Bernard Yan DMedSc, Gagan Sharma, Patricia M Desmond, Mark W Parsons, Geoffrey Alan Donnan, Stephen M Davis, Bruce C. V. Campbell
Neurology Mar 2023, 10.1212/WNL.0000000000207138; DOI: 10.1212/WNL.0000000000207138

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Abstract

Background and Objective: The safety and efficacy of tenecteplase in patients with tandem lesion stroke is unknown. We performed a comparative analysis of tenecteplase versus alteplase in patients with tandem lesions.

Methods: We first compared the treatment effect of tenecteplase and alteplase in patients with tandem lesions using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day mRS with ordinal logistic and Firth regression models. Because two key outcomes, mortality and symptomatic intracranial hemorrhage, were few in number among those who received alteplase in the EXTEND-IA TNK trials, we generated pooled estimates for these outcomes by supplementing trial data with estimates of incidence obtained through a meta-analysis of studies identified in a systematic review. We then calculated unadjusted risk differences to compare the pooled estimates for those receiving alteplase with the incidence observed in the trial among those receiving tenecteplase.

Results: Seventy-one of 483 patients (15%) in the EXTEND-IA TNK trials possessed a tandem lesion. In tandem lesion patients, intracranial reperfusion was observed in 11/56 (20%) of tenecteplase treated patients vs. 1/15 (7%) alteplase treated patients (aOR: 2.19; 95% CI:0.28-17.29). No significant difference in 90-day mRS was observed (adjusted common OR: 1.48; 95% CI: 0.44-5.00). A pooled study-level proportion of alteplase associated mortality and symptomatic intracranial hemorrhage was 0.14 (95% CI: 0.08-0.21) and 0.09 (95% CI: 0.04-0.16), respectively. Compared to a mortality rate of 0.09 (95% CI: 0.03-0.20) and a symptomatic intracranial hemorrhage rate of 0.07 (95% CI: 0.02-0.17) in tenecteplase treated patients, no significant difference was observed.

Conclusions: Functional outcomes, mortality, and symptomatic intracranial hemorrhage did not significantly differ between tenecteplase and alteplase treated tandem lesion patients.

Classification of Evidence: This study provides Class III evidence that tenecteplase is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and symptomatic intracranial hemorrhage compared with alteplase, in patients with acute stroke due to tandem lesions. However, the confidence intervals do not rule out clinically important differences.

  • Received July 6, 2022.
  • Accepted in final form January 18, 2023.
  • © 2023 American Academy of Neurology

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