Safety and efficacy of tenecteplase and alteplase in patients with tandem lesion stroke : a post hoc analysis of the EXTEND-IA TNK trials

V. Yogendrakumar; L. Churilov; P. J. Mitchell; T. J. Kleinig; N. Yassi; V. Thijs; T. Wu; D. Shah; P. Bailey; H. M. Dewey; P. M. C. Choi; A. Ma; T. Wijeratne; C. Garcia-Esperon; G. Cloud; R. V. Chandra; D. J. Cordato; B. Yan; G. Sharma; P. M. Desmond; M. W. Parsons; G. A. Donnan; S. M. Davis; Bruce C. V. Campbell; R. Dowling; S. Bush; R. Scroop; M. Simpson; M. Brooks; H. Asadi; T. Ang; F. Miteff; C. Levi; E. Rodrigues; H. Zhao; F. Ng; F. Alemseged; P. Salvaris; H. Rice; L. de Villiers; H. Brown; K. Redmond; D. Leggett; J. Fink; W. Collecutt; T. Kraemer; C. Muller; A. Coulthard; K. Mitchell; J. Clouston; K. Mahady; D. Field; B. O'Brien; B. Clissold; A. Clissold; L. Bolitho; L. Bonavia; A. Bhattacharya; A. Wright; A. Mamun; F. O'Rourke; J. Worthington; A. Wong; H. Ma; T. Phan; W. Chong; L. -A. Slater; M. Krause; T. Harrington; K. Faulder; B. Steinfort; C. Bladin

doi:10.1212/WNL.0000000000207138

Safety and efficacy of tenecteplase and alteplase in patients with tandem lesion stroke : a post hoc analysis of the EXTEND-IA TNK trials

V. Yogendrakumar, L. Churilov, P. J. Mitchell, T. J. Kleinig, N. Yassi, V. Thijs, T. Wu, D. Shah, P. Bailey, H. M. Dewey, P. M. C. Choi, A. Ma, T. Wijeratne, C. Garcia-Esperon, G. Cloud, R. V. Chandra, D. J. Cordato, B. Yan, G. Sharma, P. M. DesmondM. W. Parsons, G. A. Donnan, S. M. Davis, Bruce C. V. Campbell, R. Dowling, S. Bush, R. Scroop, M. Simpson, M. Brooks, H. Asadi, T. Ang, F. Miteff, C. Levi, E. Rodrigues, H. Zhao, F. Ng, F. Alemseged, P. Salvaris, H. Rice, L. de Villiers, H. Brown, K. Redmond, D. Leggett, J. Fink, W. Collecutt, T. Kraemer, C. Muller, A. Coulthard, K. Mitchell, J. Clouston, K. Mahady, D. Field, B. O'Brien, B. Clissold, A. Clissold, L. Bolitho, L. Bonavia, A. Bhattacharya, A. Wright, A. Mamun, F. O'Rourke, J. Worthington, A. Wong, H. Ma, T. Phan, W. Chong, L. -A. Slater, M. Krause, T. Harrington, K. Faulder, B. Steinfort, C. Bladin

Western Sydney University

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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.

Original language	English
Pages (from-to)	E1900-E1911
Number of pages	12
Journal	Neurology
Volume	100
Issue number	18
DOIs	https://doi.org/10.1212/WNL.0000000000207138
Publication status	Published - 2 May 2023

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Publisher Copyright:
© American Academy of Neurology.

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10.1212/WNL.0000000000207138

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Yogendrakumar, V., Churilov, L., Mitchell, P. J., Kleinig, T. J., Yassi, N., Thijs, V., Wu, T., Shah, D., Bailey, P., Dewey, H. M., Choi, P. M. C., Ma, A., Wijeratne, T., Garcia-Esperon, C., Cloud, G., Chandra, R. V., Cordato, D. J., Yan, B., Sharma, G., ... Bladin, C. (2023). Safety and efficacy of tenecteplase and alteplase in patients with tandem lesion stroke : a post hoc analysis of the EXTEND-IA TNK trials. Neurology, 100(18), E1900-E1911. https://doi.org/10.1212/WNL.0000000000207138

@article{524495746f02437fa8f9b033b9d08141,

title = "Safety and efficacy of tenecteplase and alteplase in patients with tandem lesion stroke : a post hoc analysis of the EXTEND-IA TNK trials",

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.",

author = "V. Yogendrakumar and L. Churilov and Mitchell, {P. J.} and Kleinig, {T. J.} and N. Yassi and V. Thijs and T. Wu and D. Shah and P. Bailey and Dewey, {H. M.} and Choi, {P. M. C.} and A. Ma and T. Wijeratne and C. Garcia-Esperon and G. Cloud and Chandra, {R. V.} and Cordato, {D. J.} and B. Yan and G. Sharma and Desmond, {P. M.} and Parsons, {M. W.} and Donnan, {G. A.} and Davis, {S. M.} and Campbell, {Bruce C. V.} and R. Dowling and S. Bush and R. Scroop and M. Simpson and M. Brooks and H. Asadi and T. Ang and F. Miteff and C. Levi and E. Rodrigues and H. Zhao and F. Ng and F. Alemseged and P. Salvaris and H. Rice and {de Villiers}, L. and H. Brown and K. Redmond and D. Leggett and J. Fink and W. Collecutt and T. Kraemer and C. Muller and A. Coulthard and K. Mitchell and J. Clouston and K. Mahady and D. Field and B. O'Brien and B. Clissold and A. Clissold and L. Bolitho and L. Bonavia and A. Bhattacharya and A. Wright and A. Mamun and F. O'Rourke and J. Worthington and A. Wong and H. Ma and T. Phan and W. Chong and Slater, {L. -A.} and M. Krause and T. Harrington and K. Faulder and B. Steinfort and C. Bladin",

note = "Publisher Copyright: {\textcopyright} American Academy of Neurology.",

year = "2023",

month = may,

day = "2",

doi = "10.1212/WNL.0000000000207138",

language = "English",

volume = "100",

pages = "E1900--E1911",

journal = "Neurology",

issn = "0028-3878",

publisher = "Lippincott Williams and Wilkins",

number = "18",

}

Yogendrakumar, V, Churilov, L, Mitchell, PJ, Kleinig, TJ, Yassi, N, Thijs, V, Wu, T, Shah, D, Bailey, P, Dewey, HM, Choi, PMC, Ma, A, Wijeratne, T, Garcia-Esperon, C, Cloud, G, Chandra, RV, Cordato, DJ, Yan, B, Sharma, G, Desmond, PM, Parsons, MW, Donnan, GA, Davis, SM, Campbell, BCV, Dowling, R, Bush, S, Scroop, R, Simpson, M, Brooks, M, Asadi, H, Ang, T, Miteff, F, Levi, C, Rodrigues, E, Zhao, H, Ng, F, Alemseged, F, Salvaris, P, Rice, H, de Villiers, L, Brown, H, Redmond, K, Leggett, D, Fink, J, Collecutt, W, Kraemer, T, Muller, C, Coulthard, A, Mitchell, K, Clouston, J, Mahady, K, Field, D, O'Brien, B, Clissold, B, Clissold, A, Bolitho, L, Bonavia, L, Bhattacharya, A, Wright, A, Mamun, A, O'Rourke, F, Worthington, J, Wong, A, Ma, H, Phan, T, Chong, W, Slater, L-A, Krause, M, Harrington, T, Faulder, K, Steinfort, B & Bladin, C 2023, 'Safety and efficacy of tenecteplase and alteplase in patients with tandem lesion stroke : a post hoc analysis of the EXTEND-IA TNK trials', Neurology, vol. 100, no. 18, pp. E1900-E1911. https://doi.org/10.1212/WNL.0000000000207138

TY - JOUR

T1 - Safety and efficacy of tenecteplase and alteplase in patients with tandem lesion stroke : a post hoc analysis of the EXTEND-IA TNK trials

AU - Yogendrakumar, V.

AU - Churilov, L.

AU - Mitchell, P. J.

AU - Kleinig, T. J.

AU - Yassi, N.

AU - Thijs, V.

AU - Wu, T.

AU - Shah, D.

AU - Bailey, P.

AU - Dewey, H. M.

AU - Choi, P. M. C.

AU - Ma, A.

AU - Wijeratne, T.

AU - Garcia-Esperon, C.

AU - Cloud, G.

AU - Chandra, R. V.

AU - Cordato, D. J.

AU - Yan, B.

AU - Sharma, G.

AU - Desmond, P. M.

AU - Parsons, M. W.

AU - Donnan, G. A.

AU - Davis, S. M.

AU - Campbell, Bruce C. V.

AU - Dowling, R.

AU - Bush, S.

AU - Scroop, R.

AU - Simpson, M.

AU - Brooks, M.

AU - Asadi, H.

AU - Ang, T.

AU - Miteff, F.

AU - Levi, C.

AU - Rodrigues, E.

AU - Zhao, H.

AU - Ng, F.

AU - Alemseged, F.

AU - Salvaris, P.

AU - Rice, H.

AU - de Villiers, L.

AU - Brown, H.

AU - Redmond, K.

AU - Leggett, D.

AU - Fink, J.

AU - Collecutt, W.

AU - Kraemer, T.

AU - Muller, C.

AU - Coulthard, A.

AU - Mitchell, K.

AU - Clouston, J.

AU - Mahady, K.

AU - Field, D.

AU - O'Brien, B.

AU - Clissold, B.

AU - Clissold, A.

AU - Bolitho, L.

AU - Bonavia, L.

AU - Bhattacharya, A.

AU - Wright, A.

AU - Mamun, A.

AU - O'Rourke, F.

AU - Worthington, J.

AU - Wong, A.

AU - Ma, H.

AU - Phan, T.

AU - Chong, W.

AU - Slater, L. -A.

AU - Krause, M.

AU - Harrington, T.

AU - Faulder, K.

AU - Steinfort, B.

AU - Bladin, C.

PY - 2023/5/2

Y1 - 2023/5/2

N2 - 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.

AB - 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.

UR - https://hdl.handle.net/1959.7/uws:77888

U2 - 10.1212/WNL.0000000000207138

DO - 10.1212/WNL.0000000000207138

M3 - Article

SN - 0028-3878

VL - 100

SP - E1900-E1911

JO - Neurology

JF - Neurology

IS - 18

ER -

Safety and efficacy of tenecteplase and alteplase in patients with tandem lesion stroke : a post hoc analysis of the EXTEND-IA TNK trials

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