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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dc.contributor.authorYogendrakumar, V.
dc.contributor.authorChurilov, L.
dc.contributor.authorMitchell, P.J.
dc.contributor.authorKleinig, T.J.
dc.contributor.authorYassi, N.
dc.contributor.authorThijs, V.
dc.contributor.authorWu, T.
dc.contributor.authorShah, D.
dc.contributor.authorBailey, P.
dc.contributor.authorDewey, H.M.
dc.contributor.authorChoi, P.M.
dc.contributor.authorMa, A.
dc.contributor.authorWijeratne, T.
dc.contributor.authorGarcia-Esperon, C.
dc.contributor.authorCloud, G.
dc.contributor.authorChandra, R.V.
dc.contributor.authorCordato, D.J.
dc.contributor.authorYan DMedSc, B.
dc.contributor.authorSharma, G.
dc.contributor.authorDesmond, P.M.
dc.contributor.authoret al.
dc.date.issued2023
dc.description.abstractBackground 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.
dc.description.statementofresponsibilityVignan Yogendrakumar, Leonid Churilov, Peter J. Mitchell, Timothy J. Kleinig, Nawaf Yassi, Vincent Thijs, Teddy Wu, Darshan Shah, Peter Bailey, Helen M. Dewey, Philip M.C. Choi, Alice Ma, Tissa Wijeratne, Carlos Garcia-Esperon, Geoffrey Cloud, Ronil V. Chandra, Dennis J. Cordato, Bernard Yan, Gagan Sharma, Patricia M. Desmond, Mark W. Parsons, Geoffrey A. Donnan, Stephen M. Davis, Bruce C.V. Campbell, for the EXTEND-IA TNK Investigators
dc.identifier.citationNeurology, 2023; 100(18):e1900-e1911
dc.identifier.doi10.1212/wnl.0000000000207138
dc.identifier.issn0028-3878
dc.identifier.issn1526-632X
dc.identifier.orcidKleinig, T.J. [0000-0003-4430-3276]
dc.identifier.urihttps://hdl.handle.net/2440/138812
dc.language.isoen
dc.publisherOvid Technologies (Wolters Kluwer Health)
dc.rights© 2023, American Academy of Neurology
dc.source.urihttps://doi.org/10.1212/wnl.0000000000207138
dc.subjectEXTEND-IA TNK Investigators
dc.subjectHumans
dc.subjectBrain Ischemia
dc.subjectIntracranial Hemorrhages
dc.subjectTissue Plasminogen Activator
dc.subjectFibrinolytic Agents
dc.subjectTreatment Outcome
dc.subjectStroke
dc.subjectTenecteplase
dc.subject.meshHumans
dc.subject.meshBrain Ischemia
dc.subject.meshIntracranial Hemorrhages
dc.subject.meshTissue Plasminogen Activator
dc.subject.meshFibrinolytic Agents
dc.subject.meshTreatment Outcome
dc.subject.meshStroke
dc.subject.meshTenecteplase
dc.titleSafety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post-Hoc Analysis of the EXTEND-IA TNK Trials
dc.typeJournal article
pubs.publication-statusPublished

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