Tenecteplase compared to alteplase in real-world outcome: A Swedish Stroke Register study
Keywords:
ischemic stroke, intravenous thrombolysis, tenecteplase, alteplase
Abstract
Background: Tenecteplase is increasingly used off-label as an alternative to alteplase for ischemic stroke thrombolysis. Our aim was to evaluate the safety of tenecteplase versus alteplase in comprehensive real-world data.
Methods: We compared the outcomes for adult patients with acute ischemic stroke treated with alteplase or tenecteplase, registered in the Swedish Stroke Register between January 1, 2018 and December 31, 2020. The primary outcome was symptomatic intracerebral hemorrhage or death during hospital stay. Secondary outcomes were death within 90 days, modified Rankin Scale at 90 days, and mean door-to-needle time (DNT).
Results: There were no significant differences in age or risk factors between 6,560 patients (45% women, mean age 74) treated with alteplase and 888 patients (43% women, mean age 74) treated with tenecteplase, although tenecteplase was more commonly used in non-university hospitals, hospitals with high use of thrombolysis, and in wake-up strokes. Tenecteplase was not non-inferior compared to alteplase in terms of symptomatic intracerebral hemorrhage or death during hospital stay (13.2% vs. 10.7%, absolute risk difference [95% confidence interval, CI] 2.5% [0.1 to 4.9%], adjusted odds ratio 1.44 [1.07–1.94]). There were no significant differences in functional outcome or death at 90 days, but tenecteplase was associated with decreased DNT (mean difference 9 min).
Conclusion: Tenecteplase was not non-inferior in safety outcome, although associated with decreased DNT. As accumulating randomized controlled studies support the non-inferiority of tenecteplase regarding functional outcome, it is important to keep scrutinizing the safety outcomes.
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References
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24. Hall J, Thon JM, Heslin M, Thau L, Yeager T, Siegal T, et al. Tenecteplase improves door-to-needle time in real-world acute stroke treatment. Stroke Vasc Interv Neurol. 2021;1:e000102. doi: 10.1161/SVIN.121.000102
25. Lees KR, Emberson J, Blackwell L, Bluhmki E, Davis SM, Donnan GA, et al. Effects of alteplase for acute stroke on the distribution of functional outcomes: a pooled analysis of 9 trials. Stroke. 2016;47:2373–9. doi: 10.1161/STROKEAHA.116.013644
26. Darehed D, Blom M, Glader EL, Niklasson J, Norrving B, Eriksson M. In-hospital delays in stroke thrombolysis: every minute counts. Stroke. 2020;51:2536–9. doi: 10.1161/STROKEAHA.120.029468
27. Yogendrakumar V, Churilov L, Mitchell PJ, Kleinig TJ, Yassi N, Thijs V, et al. Safety and efficacy of tenecteplase in older patients with large vessel occlusion: a pooled analysis of the EXTEND-IA TNK trials. Neurology. 2022;98:e1292–301. doi: 10.1212/WNL.0000000000013302
28. Thommessen B, Næss H, Logallo N, Kvistad CE, Waje-Andreassen U, Ihle-Hansen H, et al. Tenecteplase versus alteplase after acute ischemic stroke at high age. Int J Stroke Off J Int Stroke Soc. 2021;16:295–9. doi: 10.1177/1747493020938306
29. Chaisinanunkul N, Adeoye O, Lewis RJ, Grotta JC, Broderick J, Jovin TG, et al. Adopting a patient-centered approach to primary outcome analysis of acute stroke trials by use of a utility-weighted modified Rankin scale. Stroke J Cereb Circ. 2015;46:2238–43. doi: 10.1161/STROKEAHA.114.008547
30. Wang Y, Li S, Pan Y, Li H, Parsons MW, Campbell BCV, et al. Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial. Lancet. 2023;401:645–54. doi: 10.1016/S0140-6736(22)02600-9
2. Berge E, Whiteley W, Audebert H, De Marchis GM, Fonseca AC, Padiglioni C, et al. European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke. Eur Stroke J. 2021;6:I–LXII. doi: 10.1177/2396987321989865
3. Tanswell P, Modi N, Combs D, Danays T. Pharmacokinetics and pharmacodynamics of tenecteplase in fibrinolytic therapy of acute myocardial infarction. Clin Pharmacokinet. 2002;41:1229–45. doi: 10.2165/00003088-200241150-00001
4. Burgos AM, Saver JL. Evidence that tenecteplase is noninferior to alteplase for acute ischemic stroke: meta-analysis of 5 randomized trials. Stroke. 2019;50:2156–62. doi: 10.1161/strokeaha.119.025080
5. Menon BK, Buck BH, Singh N, Deschaintre Y, Almekhlafi MA, Coutts SB, et al. Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT): a pragmatic, multicentre, open-label, registry-linked, randomised, controlled, non-inferiority trial. Lancet. 2022;400:161–69. doi: 10.1016/S0140-6736(22)01054-6
6. Bivard A, Huang X, Levi CR, Spratt N, Campbell BCV, Cheripelli BK, et al. Tenecteplase in ischemic stroke offers improved recanalization: analysis of 2 trials. Neurology. 2017;89:62–7. doi: 10.1212/WNL.0000000000004062
7. Coutts SB, Berge E, Campbell BC, Muir KW, Parsons MW. Tenecteplase for the treatment of acute ischemic stroke: a review of completed and ongoing randomized controlled trials. Int J Stroke. 2018;13:885–92. doi: 10.1177/1747493018790024
8. Katsanos AH, Psychogios K, Turc G, Sacco S, de Sousa DA, De Marchis GM, et al. Off-label use of tenecteplase for the treatment of acute ischemic stroke: a systematic review and meta-analysis. JAMA Netw Open. 2022;5:e224506. doi: 10.1001/jamanetworkopen.2022.4506
9. Gerschenfeld G, Liegey JS, Laborne FX, Yger M, Lyon V, Checkouri T, et al. Treatment times, functional outcome, and hemorrhage rates after switching to tenecteplase for stroke thrombolysis: insights from the TETRIS registry. Eur Stroke J. 2022;7:358–64. doi: 10.1177/23969873221113729
10. Zhong CS, Beharry J, Salazar D, Smith K, Withington S, Campbell BCV, et al. Routine use of tenecteplase for thrombolysis in acute ischemic stroke. Stroke. 2021;52:1087–90. doi: 10.1161/strokeaha.120.030859
11. Tsivgoulis G, Katsanos AH, Christogiannis C, Faouzi B, Mavridis D, Dixit AK, et al. Intravenous thrombolysis with tenecteplase for the treatment of acute ischemic stroke. Ann Neurol. 2022;92(3):349–57. doi: 10.1002/ana.26445.
12. Alamowitch S, Turc G, Palaiodimou L, Bivard A, Cameron A, De Marchis GM, et al. European Stroke Organisation (ESO) expedited recommendation on tenecteplase for acute ischaemic stroke. Eur Stroke J. 2023;8:8–54. doi: 10.1177/23969873221150022
13. Socialstyrelsen. Nationella riktlinjer för vård vid stroke. 2020-1–6545, Socialstyrelsen; 2020. Available from: https://www.socialstyrelsen.se/globalassets/sharepoint-dokument/artikelkatalog/nationella-riktlinjer/2020-1-6545.pdf [cited 15 April 2022].
14. Riksstroke. Stroke Och TIA, Årsrapport Från Riksstroke 2020. Report, Riksstroke; 2021. Available from: https://www.riksstroke.org/wp-content/uploads/2021/12/Riksstroke_Arsrapport_2020.pdf [cited 23 March 2022].
15. Söderholm A, Stegmayr B, Glader EL, Asplund K; Riksstroke Collaboration. Validation of Hospital performance measures of acute stroke care quality. Riksstroke, the Swedish Stroke Register. Neuroepidemiology. 2016;46:229–34. doi: 10.1159/000444679
16. Kasner SE. Clinical interpretation and use of stroke scales. Lancet Neurol. 2006;5:603–12. doi: 10.1016/s1474-4422(06)70495-1
17. Eriksson M, Appelros P, Norrving B, Terént A, Stegmayr B. Assessment of functional outcome in a national quality register for acute stroke: can simple self-reported items be transformed into the modified Rankin Scale? Stroke. 2007;38:1384–6. doi: 10.1161/01.STR.0000260102.97954.9c
18. Kvistad CE, Næss H, Helleberg BH, Idicula T, Hagberg G, Nordby LM, et al. Tenecteplase versus alteplase for the management of acute ischaemic stroke in Norway (NOR-TEST 2, part A): a phase 3, randomised, open-label, blinded endpoint, non-inferiority trial. Lancet Neurol. 2022;21:511–9. doi: 10.1016/S1474-4422(22)00124-7
19. Riksstroke. Stroke Och TIA, Årsrapport Från Riksstroke 2019. Report, Riksstroke; 2020. Available from: https://www.riksstroke.org/wp-content/uploads/2020/09/Riksstroke_A%CC%8Arsrapport-2019_slutversionWEB-1.pdf [cited 23 March 2022].
20. Riksstroke. Stroke Och TIA, Årsrapport Från Riksstroke 2018. Report, Riksstroke; 2019. Available from: https://www.riksstroke.org/wp-content/uploads/2019/09/Riksstroke_A%CC%8Arsrapport-2018_slutversionWEB.pdf [cited 23 March 2022].
21. Campbell BCV, Mitchell PJ, Churilov L, Yassi N, Kleinig TJ, Dowling RJ, et al. Effect of intravenous tenecteplase dose on cerebral reperfusion before thrombectomy in patients with large vessel occlusion ischemic stroke: the EXTEND-IA TNK part 2 randomized clinical trial. JAMA. 2020;323:1257–65. doi: 10.1001/jama.2020.1511
22. Warach SJ, Dula AN, Milling TJ, Miller S, Allen L, Zuck ND, et al. Prospective observational cohort study of tenecteplase versus alteplase in routine clinical practice. Stroke. 2022;53:3583–93. doi: 10.1161/STROKEAHA.122.038950
23. Mahawish K, Gommans J, Kleinig T, Lallu B, Tyson A, Ranta A. Switching to tenecteplase for stroke thrombolysis: real-world experience and outcomes in a regional stroke network. Stroke. 2021;52:e590–3. doi: 10.1161/STROKEAHA.121.035931
24. Hall J, Thon JM, Heslin M, Thau L, Yeager T, Siegal T, et al. Tenecteplase improves door-to-needle time in real-world acute stroke treatment. Stroke Vasc Interv Neurol. 2021;1:e000102. doi: 10.1161/SVIN.121.000102
25. Lees KR, Emberson J, Blackwell L, Bluhmki E, Davis SM, Donnan GA, et al. Effects of alteplase for acute stroke on the distribution of functional outcomes: a pooled analysis of 9 trials. Stroke. 2016;47:2373–9. doi: 10.1161/STROKEAHA.116.013644
26. Darehed D, Blom M, Glader EL, Niklasson J, Norrving B, Eriksson M. In-hospital delays in stroke thrombolysis: every minute counts. Stroke. 2020;51:2536–9. doi: 10.1161/STROKEAHA.120.029468
27. Yogendrakumar V, Churilov L, Mitchell PJ, Kleinig TJ, Yassi N, Thijs V, et al. Safety and efficacy of tenecteplase in older patients with large vessel occlusion: a pooled analysis of the EXTEND-IA TNK trials. Neurology. 2022;98:e1292–301. doi: 10.1212/WNL.0000000000013302
28. Thommessen B, Næss H, Logallo N, Kvistad CE, Waje-Andreassen U, Ihle-Hansen H, et al. Tenecteplase versus alteplase after acute ischemic stroke at high age. Int J Stroke Off J Int Stroke Soc. 2021;16:295–9. doi: 10.1177/1747493020938306
29. Chaisinanunkul N, Adeoye O, Lewis RJ, Grotta JC, Broderick J, Jovin TG, et al. Adopting a patient-centered approach to primary outcome analysis of acute stroke trials by use of a utility-weighted modified Rankin scale. Stroke J Cereb Circ. 2015;46:2238–43. doi: 10.1161/STROKEAHA.114.008547
30. Wang Y, Li S, Pan Y, Li H, Parsons MW, Campbell BCV, et al. Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2): a phase 3, multicentre, open-label, randomised controlled, non-inferiority trial. Lancet. 2023;401:645–54. doi: 10.1016/S0140-6736(22)02600-9
Published
2024-10-09
How to Cite
Skärlund M., Åsberg S., Eriksson M., & Lundström E. (2024). Tenecteplase compared to alteplase in real-world outcome: A Swedish Stroke Register study. Upsala Journal of Medical Sciences, 129, e10459. https://doi.org/10.48101/ujms.v129.10459
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Original Articles
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