Safety and Efficacy of Tenecteplase and Alteplase in Patients With Tandem Lesion Stroke: A Post Hoc Analysis of the EXTEND-IA TNK Trials. (2nd May 2023)

• Record Type: Journal Article
• Authors: Yogendrakumar, Vignan; Churilov, Leonid; Mitchell, Peter J.; Kleinig, Timothy J.; Yassi, Nawaf; Thijs, Vincent; Wu, Teddy; Shah, Darshan; Bailey, Peter; Dewey, Helen M.; Choi, Philip M.C.; Ma, Alice; Wijeratne, Tissa; Garcia-Esperon, Carlos; Cloud, Geoffrey; Chandra, Ronil V.; Cordato, Dennis J.; Yan, Bernard; Sharma, Gagan; Desmond, Patricia M.; Parsons, Mark W.; Donnan, Geoffrey A.; Davis, Stephen M.; Campbell, Bruce C.V.
• Other Names: author non-byline.; Dowling Richard author non-byline.; Bush Steven author non-byline.; Scroop Rebecca author non-byline.; Simpson Marion author non-byline.; Brooks Mark author non-byline.; Asadi Hamed author non-byline.; Ang Timothy author non-byline.; Miteff Ferdinand author non-byline.; Levi Christopher author non-byline.; Rodrigues Edrich author non-byline.; Zhao Henry author non-byline.; Ng Felix author non-byline.; Alemseged Fana author non-byline.; Salvaris Patrick author non-byline.; Rice Henry author non-byline.; de Villiers Laetitia author non-byline.; Brown Helen author non-byline.; Redmond Kendal author non-byline.; Leggett David author non-byline.; Fink John author non-byline.; Collecutt Wayne author non-byline.; Kraemer Thomas author non-byline.; Muller Claire author non-byline.; Coulthard Alan author non-byline.; Mitchell Ken author non-byline.; Clouston John author non-byline.; Mahady Kate author non-byline.; Field Deborah author non-byline.; O'Brien Bill author non-byline.; Clissold Benjamin author non-byline.; Clissold Anna author non-byline.; Bolitho Leslie author non-byline.; Bonavia Luke author non-byline.; Bhattacharya Arup author non-byline.; Wright Alistair author non-byline.; Mamun Abul author non-byline.; O'Rourke Fintan author non-byline.; Worthington John author non-byline.; Wong Andrew author non-byline.; Ma Henry author non-byline.; Phan Thanh author non-byline.; Chong Winston author non-byline.; Slater Lee-Anne author non-byline.; Krause Martin author non-byline.; Harrington Timothy author non-byline.; Faulder Kenneth author non-byline.; Steinfort Brendan author non-byline.; Bladin Christopher author non-byline.;
• Is Part Of: Neurology. Volume 100:Number 18(2023)
• Page Start: e1900
• Page End: e1911
• Publication Date: 2023-05-02
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000207138
• Languages: English
• ISSNs: 0028-3878

Abstract

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 .