Meta-Analysis

. 2023 May 2;100(18):e1900-e1911.

doi: 10.1212/WNL.0000000000207138. Epub 2023 Mar 6.

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

Vignan Yogendrakumar¹, Leonid Churilov², Peter J Mitchell², Timothy J Kleinig², Nawaf Yassi², Vincent Thijs², Teddy Wu², Darshan Shah², Peter Bailey², Helen M Dewey², Philip M C Choi², Alice Ma², Tissa Wijeratne², Carlos Garcia-Esperon², Geoffrey Cloud², Ronil V Chandra², Dennis J Cordato², Bernard Yan², Gagan Sharma², Patricia M Desmond², Mark W Parsons², Geoffrey A Donnan², Stephen M Davis², Bruce C V Campbell²; EXTEND-IA TNK Investigators

Collaborators, Affiliations

Collaborators

EXTEND-IA TNK Investigators:
Richard Dowling, Steven Bush, Rebecca Scroop, Marion Simpson, Mark Brooks, Hamed Asadi, Timothy Ang, Ferdinand Miteff, Christopher Levi, Edrich Rodrigues, Henry Zhao, Felix Ng, Fana Alemseged, Patrick Salvaris, Henry Rice, Laetitia de Villiers, Helen Brown, Kendal Redmond, David Leggett, John Fink, Wayne Collecutt, Thomas Kraemer, Claire Muller, Alan Coulthard, Ken Mitchell, John Clouston, Kate Mahady, Deborah Field, Bill O'Brien, Benjamin Clissold, Anna Clissold, Leslie Bolitho, Luke Bonavia, Arup Bhattacharya, Alistair Wright, Abul Mamun, Fintan O'Rourke, John Worthington, Andrew Wong, Henry Ma, Thanh Phan, Winston Chong, Lee-Anne Slater, Martin Krause, Timothy Harrington, Kenneth Faulder, Brendan Steinfort, Christopher Bladin

Affiliations

¹ From the Department of Medicine and Neurology (V.Y., L.C., N.Y., B.Y., G.S., M.W.P., G.A.D., S.M.D., B.C.V.C.), Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville; Melbourne Medical School (L.C., V.T.), University of Melbourne, Heidelberg; Department of Radiology (P.J.M., B.C.V.C.), Royal Melbourne Hospital, University of Melbourne, Parkville; Department of Neurology (T.J.K., B.Y., P.M.D.), Royal Adelaide Hospital; Population Health and Immunity Division (N.Y.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Florey Institute of Neuroscience and Mental Health (V.T.), University of Melbourne, Parkville, Australia; Department of Neurology (T. Wu), Christchurch Hospital, New Zealand; Department of Neurology (D.S.), Princess Alexandra Hospital, Brisbane; Department of Neurology (P.B.), Gold Coast University Hospital, Southport; Department of Neurosciences (H.M.D., P.M.C.C.), Eastern Health and Eastern Health Clinical School, Monash University, Clayton; Royal North Shore Hospital (A.M.), New South Wales; Department of Medicine and Neurology (T. Wijeratne), Melbourne Medical School, The University of Melbourne and Western Health, Sunshine Hospital, St Albans; Department of Neurology (C.G.-E.), John Hunter Hospital, Newcastle, New South Wales; Department of Neurology (G.C.), Alfred Hospital, Melbourne; Department of Neuroscience (G.C.), Central Clinical School, Monash University, Melbourne; NeuroInterventional Radiology Unit (R.V.C.), Monash Health, Monash University; and Department of Neurology (D.J.C., M.W.P.), Liverpool Hospital, University of New South Wales, Sydney, Australia. vyogendrakum@student.unimelb.edu.au.
² From the Department of Medicine and Neurology (V.Y., L.C., N.Y., B.Y., G.S., M.W.P., G.A.D., S.M.D., B.C.V.C.), Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville; Melbourne Medical School (L.C., V.T.), University of Melbourne, Heidelberg; Department of Radiology (P.J.M., B.C.V.C.), Royal Melbourne Hospital, University of Melbourne, Parkville; Department of Neurology (T.J.K., B.Y., P.M.D.), Royal Adelaide Hospital; Population Health and Immunity Division (N.Y.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Florey Institute of Neuroscience and Mental Health (V.T.), University of Melbourne, Parkville, Australia; Department of Neurology (T. Wu), Christchurch Hospital, New Zealand; Department of Neurology (D.S.), Princess Alexandra Hospital, Brisbane; Department of Neurology (P.B.), Gold Coast University Hospital, Southport; Department of Neurosciences (H.M.D., P.M.C.C.), Eastern Health and Eastern Health Clinical School, Monash University, Clayton; Royal North Shore Hospital (A.M.), New South Wales; Department of Medicine and Neurology (T. Wijeratne), Melbourne Medical School, The University of Melbourne and Western Health, Sunshine Hospital, St Albans; Department of Neurology (C.G.-E.), John Hunter Hospital, Newcastle, New South Wales; Department of Neurology (G.C.), Alfred Hospital, Melbourne; Department of Neuroscience (G.C.), Central Clinical School, Monash University, Melbourne; NeuroInterventional Radiology Unit (R.V.C.), Monash Health, Monash University; and Department of Neurology (D.J.C., M.W.P.), Liverpool Hospital, University of New South Wales, Sydney, Australia.

PMID: 36878701
PMCID: PMC10159769
DOI: 10.1212/WNL.0000000000207138

Meta-Analysis

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 et al. Neurology. 2023.

. 2023 May 2;100(18):e1900-e1911.

doi: 10.1212/WNL.0000000000207138. Epub 2023 Mar 6.

Authors

Collaborators

EXTEND-IA TNK Investigators:
Richard Dowling, Steven Bush, Rebecca Scroop, Marion Simpson, Mark Brooks, Hamed Asadi, Timothy Ang, Ferdinand Miteff, Christopher Levi, Edrich Rodrigues, Henry Zhao, Felix Ng, Fana Alemseged, Patrick Salvaris, Henry Rice, Laetitia de Villiers, Helen Brown, Kendal Redmond, David Leggett, John Fink, Wayne Collecutt, Thomas Kraemer, Claire Muller, Alan Coulthard, Ken Mitchell, John Clouston, Kate Mahady, Deborah Field, Bill O'Brien, Benjamin Clissold, Anna Clissold, Leslie Bolitho, Luke Bonavia, Arup Bhattacharya, Alistair Wright, Abul Mamun, Fintan O'Rourke, John Worthington, Andrew Wong, Henry Ma, Thanh Phan, Winston Chong, Lee-Anne Slater, Martin Krause, Timothy Harrington, Kenneth Faulder, Brendan Steinfort, Christopher Bladin

Affiliations

¹ From the Department of Medicine and Neurology (V.Y., L.C., N.Y., B.Y., G.S., M.W.P., G.A.D., S.M.D., B.C.V.C.), Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville; Melbourne Medical School (L.C., V.T.), University of Melbourne, Heidelberg; Department of Radiology (P.J.M., B.C.V.C.), Royal Melbourne Hospital, University of Melbourne, Parkville; Department of Neurology (T.J.K., B.Y., P.M.D.), Royal Adelaide Hospital; Population Health and Immunity Division (N.Y.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Florey Institute of Neuroscience and Mental Health (V.T.), University of Melbourne, Parkville, Australia; Department of Neurology (T. Wu), Christchurch Hospital, New Zealand; Department of Neurology (D.S.), Princess Alexandra Hospital, Brisbane; Department of Neurology (P.B.), Gold Coast University Hospital, Southport; Department of Neurosciences (H.M.D., P.M.C.C.), Eastern Health and Eastern Health Clinical School, Monash University, Clayton; Royal North Shore Hospital (A.M.), New South Wales; Department of Medicine and Neurology (T. Wijeratne), Melbourne Medical School, The University of Melbourne and Western Health, Sunshine Hospital, St Albans; Department of Neurology (C.G.-E.), John Hunter Hospital, Newcastle, New South Wales; Department of Neurology (G.C.), Alfred Hospital, Melbourne; Department of Neuroscience (G.C.), Central Clinical School, Monash University, Melbourne; NeuroInterventional Radiology Unit (R.V.C.), Monash Health, Monash University; and Department of Neurology (D.J.C., M.W.P.), Liverpool Hospital, University of New South Wales, Sydney, Australia. vyogendrakum@student.unimelb.edu.au.
² From the Department of Medicine and Neurology (V.Y., L.C., N.Y., B.Y., G.S., M.W.P., G.A.D., S.M.D., B.C.V.C.), Melbourne Brain Centre at the Royal Melbourne Hospital, Parkville; Melbourne Medical School (L.C., V.T.), University of Melbourne, Heidelberg; Department of Radiology (P.J.M., B.C.V.C.), Royal Melbourne Hospital, University of Melbourne, Parkville; Department of Neurology (T.J.K., B.Y., P.M.D.), Royal Adelaide Hospital; Population Health and Immunity Division (N.Y.), The Walter and Eliza Hall Institute of Medical Research, Parkville; Florey Institute of Neuroscience and Mental Health (V.T.), University of Melbourne, Parkville, Australia; Department of Neurology (T. Wu), Christchurch Hospital, New Zealand; Department of Neurology (D.S.), Princess Alexandra Hospital, Brisbane; Department of Neurology (P.B.), Gold Coast University Hospital, Southport; Department of Neurosciences (H.M.D., P.M.C.C.), Eastern Health and Eastern Health Clinical School, Monash University, Clayton; Royal North Shore Hospital (A.M.), New South Wales; Department of Medicine and Neurology (T. Wijeratne), Melbourne Medical School, The University of Melbourne and Western Health, Sunshine Hospital, St Albans; Department of Neurology (C.G.-E.), John Hunter Hospital, Newcastle, New South Wales; Department of Neurology (G.C.), Alfred Hospital, Melbourne; Department of Neuroscience (G.C.), Central Clinical School, Monash University, Melbourne; NeuroInterventional Radiology Unit (R.V.C.), Monash Health, Monash University; and Department of Neurology (D.J.C., M.W.P.), Liverpool Hospital, University of New South Wales, Sydney, Australia.

PMID: 36878701
PMCID: PMC10159769
DOI: 10.1212/WNL.0000000000207138

Abstract

Background and objectives: The safety and efficacy of tenecteplase (TNK) in patients with tandem lesion (TL) stroke is unknown. We performed a comparative analysis of TNK and alteplase in patients with TLs.

Methods: We first compared the treatment effect of TNK and alteplase in patients with TLs using individual patient data from the EXTEND-IA TNK trials. We evaluated intracranial reperfusion at initial angiographic assessment and 90-day modified Rankin scale (mRS) with ordinal logistic and Firth regression models. Because 2 key outcomes, mortality and symptomatic intracranial hemorrhage (sICH), 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 TNK.

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

Discussion: Functional outcomes, mortality, and sICH did not significantly differ between patients with TLs treated with TNK and those treated with alteplase.

Classification of evidence: This study provides Class III evidence that TNK is associated with similar rates of intracranial reperfusion, functional outcome, mortality, and sICH compared with alteplase in patients with acute stroke due to TLs. However, the CIs do not rule out clinically important differences. TRIAL REGISTRATION INFORMATION: clinicaltrials.gov/ct2/show/NCT02388061; clinicaltrials.gov/ct2/show/NCT03340493.

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Conflict of interest statement

V. Yogendrakumar, L. Churilov, and P.J. Mitchell reports no disclosures relevant to the manuscript. T.J. Kleinig receives educational meeting supports from Boehringer Ingelheim. N. Yassi reports no disclosures relevant to the manuscript. V. Thijs receives personal compensation from Pfizer, Boehringer Ingelheim, Medtronic, BMS, Bayer, Allergan, Amgen, Biotronik and Abbott. D. Shah has received speakers honoraria from Boehringer Ingelheim and Bayer. P. Bailey, H.M. Dewey, P.M.C. Choi, A. Ma, and T. Wijeratne report no disclosures relevant to the manuscript. C. Garcia-Esperon received funding from Boehringer Ingelheim and Bayer for conference travel. G. Cloud, R.V Chandra, D.J. Cordato, B. Yan, and G. Sharma report no disclosures relevant to the manuscript. M. Parsons is on the Global Metalyse (TNK) Advisory Board for Boehringer Ingelheim. G.A. Donnan, S.M. Davis, B.C.V. Campbell, T. Wu, and P. Desmond report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Figures

**Figure 1. mRS Scores at 90 Days Stratified by Treatment in Patients With a Tandem Lesion (A) and Without a Tandem Lesion (B)**
(A) No significant differences were observed between tenecteplase (pooled analysis of 0.25 and 0.40 mg/kg dosing) and alteplase (acOR 1.48 95% CI 0.44–5.00), adjusting for baseline NIH Stroke Scale, age, time from symptom onset to arterial puncture, and study. (B) No significant differences were observed between tenecteplase (pooled analysis of 0.25 mg/kg and 0.40 mg/kg dosing) and alteplase (acOR 1.49 95% CI 0.85–2.60), adjusting for baseline NIH Stroke Scale, age, time from symptom onset to arterial puncture, and study. acOR = adjusted common odds radio; mRS = modified Rankin scale.

**Figure 2. Study-Level Meta-analysis of Proportions of Mortality (A) and Symptomatic Intracranial Hemorrhage (B) in Patients With Tandem Lesions Treated With IV Alteplase**
ES = effect size.

See this image and copyright information in PMC

References

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Substances

Associated data

LinkOut - more resources

Full Text Sources

Medical

Research Materials