Safety and Efficacy of Tenecteplase in Older Patients With Large Vessel Occlusion: A Pooled Analysis of the EXTEND-IA TNK Trials. (22nd March 2022)

• Record Type: Journal Article
• Authors: Yogendrakumar, Vignan; Churilov, Leonid; Mitchell, Peter J.; Kleinig, Timothy J.; Yassi, Nawaf; Thijs, Vincent; Wu, Teddy Y.; Shah, Darshan G.; Ng, Felix C.; Dewey, Helen M.; Wijeratne, Tissa; Yan, Bernard; Desmond, Patricia M.; Parsons, Mark W.; Donnan, Geoffrey Alan; 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.; Zhao Henry author non-byline.; Alemseged Fana author non-byline.; Salvaris Patrick author non-byline.; GarciaEsperon Carlos author non-byline.; Bailey Peter author non-byline.; Rice Henry author non-byline.; de Villiers Laetitia author non-byline.; Choi Philip 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.; Cordato Dennis 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.; Cloud Geoffrey 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.; Chandra Ronil 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.; Sharma Gagan author non-byline.;
• Is Part Of: Neurology. Volume 98:Number 12(2022)
• Page Start: e1292
• Page End: e1301
• Publication Date: 2022-03-22
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000013302
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : Background and Objectives: Detailed study of tenecteplase (TNK) in patients older than 80 years is limited. The objective of our study was to assess the safety and efficacy of TNK at 0.25 and 0.40 mg/kg doses in patients older than 80 years with large vessel occlusion. Methods: We performed a pooled analysis of the EXTEND-IA TNK randomized controlled trials (n = 502). Patients were adults presenting with ischemic stroke due to occlusion of the intracranial internal carotid, middle cerebral, or basilar artery presenting within 4.5 hours of symptom onset. We compared the treatment effect of TNK 0.25 mg/kg, TNK 0.40 mg/kg, and alteplase 0.90 mg/kg, stratifying for patient age (>80 years). Outcomes evaluated include 90-day modified Rankin Scale (mRS) score, all-cause mortality, and symptomatic ICH. Treatment effect was adjusted for baseline NIH Stroke Score, age, and time from symptom onset to puncture via mixed effects proportional odds and logistic regression models. Results: In patients >80 years (n = 137), TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, adjusted common odds ratio (acOR) 2.70, 95% CI 1.23–5.94) and reduced mortality (acOR 0.34, 95% CI 0.13–0.91) vs 0.40 mg/kg. TNK 0.25 mg/kg was associated with improved 90-day mRS (median 3 vs 4, acOR 2.28, 95% CI 1.03–5.05) vs alteplase. No difference in 90-day mRS or mortality was detected between alteplase and TNK 0.40 mg/kg. Symptomatic ICH was observed in 4 patients treated with TNK 0.40 mg/kg, 1 patient treated with alteplase, and 0 patients treated with TNK 0.25 mg/kg. In patients ≤80 years, no differences in 90-day mRS, mortality, or symptomatic ICH were observed among TNK 0.25 mg/kg, alteplase, and TNK 0.40 mg/kg. Discussion: TNK 0.25 mg/kg was associated with improved 90-day mRS and lower mortality in patients older than 80 years. No differences among the doses were observed in younger patients. Trial Registration Information: NCT02388061, NCT03340493. Classification of Evidence: This study provides Class II evidence that tenecteplase 0.25 mg/kg given before endovascular therapy in patients >80 years old with large vessel occlusion stroke is associated with better functional outcomes at 90 days and reduced mortality when compared to tenecteplase 0.40 mg/kg or alteplase 0.90 mg/kg.