Tenecteplase versus Alteplase before Thrombectomy for Ischemic Stroke
Bruce C V Campbell, Peter J Mitchell, Leonid Churilov, Nawaf Yassi, Timothy J Kleinig, Richard J Dowling, Bernard Yan, Steven J Bush, Helen M Dewey, Vincent Thijs, Rebecca Scroop, Marion Simpson, Mark Brooks, Hamed Asadi, Teddy Y Wu, Darshan G Shah, Tissa Wijeratne, Timothy Ang, Ferdinand Miteff, Christopher R Levi, Edrich Rodrigues, Henry Zhao, Patrick Salvaris, Carlos Garcia-Esperon, Peter Bailey, Henry Rice, Laetitia de Villiers, Helen Brown, Kendal Redmond, David Leggett, John N Fink, Wayne Collecutt, Andrew A Wong, Claire Muller, Alan Coulthard, Ken Mitchell, John Clouston, Kate Mahady, Deborah Field, Henry Ma, Thanh G Phan, Winston Chong, Ronil V Chandra, Lee-Anne Slater, Martin Krause, Timothy J Harrington, Kenneth C Faulder, Brendan S Steinfort, Christopher F Bladin, Gagan Sharma, Patricia M Desmond, Mark W Parsons, Geoffrey A Donnan, Stephen M Davis, EXTEND-IA TNK Investigators, T J Oxley, A McDonald, D Jackson, J Tsoleridis, L Pesavento, J Taylor, E Cheong, A Balabanski, M Waters, R Drew, J Cranefield, P S Loh, P M Choi, A K Gilligan, S Coote, T Frost, Z Ross, G Thomas, A Brodtmann, F C Ng, B Coulton, D Young, H Tu, E Mackey, S Celestino, E Low, A Sabet, S Mishra, B Urbi, N Spratt, L Kaauwai, M Holt, K Wong, W Vallat, V Maxwell, S Day, J Eagle, P A Barber, B McGuinness, A Hope, M Moriarty, L Zhao, G Cloud, A Madan, A Moore, E Cowley, R McCoy, M Sallaberger, B Snow, J Kolbe, R Stark, J King, R Macdonnell, J Attia, C D’Este, Bruce C V Campbell, Peter J Mitchell, Leonid Churilov, Nawaf Yassi, Timothy J Kleinig, Richard J Dowling, Bernard Yan, Steven J Bush, Helen M Dewey, Vincent Thijs, Rebecca Scroop, Marion Simpson, Mark Brooks, Hamed Asadi, Teddy Y Wu, Darshan G Shah, Tissa Wijeratne, Timothy Ang, Ferdinand Miteff, Christopher R Levi, Edrich Rodrigues, Henry Zhao, Patrick Salvaris, Carlos Garcia-Esperon, Peter Bailey, Henry Rice, Laetitia de Villiers, Helen Brown, Kendal Redmond, David Leggett, John N Fink, Wayne Collecutt, Andrew A Wong, Claire Muller, Alan Coulthard, Ken Mitchell, John Clouston, Kate Mahady, Deborah Field, Henry Ma, Thanh G Phan, Winston Chong, Ronil V Chandra, Lee-Anne Slater, Martin Krause, Timothy J Harrington, Kenneth C Faulder, Brendan S Steinfort, Christopher F Bladin, Gagan Sharma, Patricia M Desmond, Mark W Parsons, Geoffrey A Donnan, Stephen M Davis, EXTEND-IA TNK Investigators, T J Oxley, A McDonald, D Jackson, J Tsoleridis, L Pesavento, J Taylor, E Cheong, A Balabanski, M Waters, R Drew, J Cranefield, P S Loh, P M Choi, A K Gilligan, S Coote, T Frost, Z Ross, G Thomas, A Brodtmann, F C Ng, B Coulton, D Young, H Tu, E Mackey, S Celestino, E Low, A Sabet, S Mishra, B Urbi, N Spratt, L Kaauwai, M Holt, K Wong, W Vallat, V Maxwell, S Day, J Eagle, P A Barber, B McGuinness, A Hope, M Moriarty, L Zhao, G Cloud, A Madan, A Moore, E Cowley, R McCoy, M Sallaberger, B Snow, J Kolbe, R Stark, J King, R Macdonnell, J Attia, C D’Este
Abstract
Background: Intravenous infusion of alteplase is used for thrombolysis before endovascular thrombectomy for ischemic stroke. Tenecteplase, which is more fibrin-specific and has longer activity than alteplase, is given as a bolus and may increase the incidence of vascular reperfusion.
Methods: We randomly assigned patients with ischemic stroke who had occlusion of the internal carotid, basilar, or middle cerebral artery and who were eligible to undergo thrombectomy to receive tenecteplase (at a dose of 0.25 mg per kilogram of body weight; maximum dose, 25 mg) or alteplase (at a dose of 0.9 mg per kilogram; maximum dose, 90 mg) within 4.5 hours after symptom onset. The primary outcome was reperfusion of greater than 50% of the involved ischemic territory or an absence of retrievable thrombus at the time of the initial angiographic assessment. Noninferiority of tenecteplase was tested, followed by superiority. Secondary outcomes included the modified Rankin scale score (on a scale from 0 [no neurologic deficit] to 6 [death]) at 90 days. Safety outcomes were death and symptomatic intracerebral hemorrhage.
Results: Of 202 patients enrolled, 101 were assigned to receive tenecteplase and 101 to receive alteplase. The primary outcome occurred in 22% of the patients treated with tenecteplase versus 10% of those treated with alteplase (incidence difference, 12 percentage points; 95% confidence interval [CI], 2 to 21; incidence ratio, 2.2; 95% CI, 1.1 to 4.4; P=0.002 for noninferiority; P=0.03 for superiority). Tenecteplase resulted in a better 90-day functional outcome than alteplase (median modified Rankin scale score, 2 vs. 3; common odds ratio, 1.7; 95% CI, 1.0 to 2.8; P=0.04). Symptomatic intracerebral hemorrhage occurred in 1% of the patients in each group.
Conclusions: Tenecteplase before thrombectomy was associated with a higher incidence of reperfusion and better functional outcome than alteplase among patients with ischemic stroke treated within 4.5 hours after symptom onset. (Funded by the National Health and Medical Research Council of Australia and others; EXTEND-IA TNK ClinicalTrials.gov number, NCT02388061 .).
Source: PubMed