Xuya Huang1, Rachael MacIsaac2, John Lp Thompson3, Bruce Levin3, Richard Buchsbaum3, E Clarke Haley4, Christopher Levi5, Bruce Campbell6, Christopher Bladin7, Mark Parsons5, Keith W Muir8. 1. Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK. 2. Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. 3. Department of Biostatistics, Columbia University, New York, USA. 4. Department of Neurology, University of Virginia, Charlottesville, USA. 5. Department of Neurology, University of Newcastle, Newcastle, Australia. 6. Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. 7. The Department of Neurosciences, Monash University, Melbourne, Australia. 8. Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK keith.muir@glasgow.ac.uk.
Abstract
BACKGROUND: Tenecteplase, a modified plasminogen activator with higher fibrin specificity and longer half-life, may have advantages over alteplase in acute ischemic stroke thrombolysis. AIMS: We undertook an individual patient data meta-analysis of randomized controlled trials that compared alteplase with tenecteplase in acute stroke. METHODS: Eligible studies were identified by a MEDLINE search, and individual patient data were acquired. We compared clinical outcomes including modified Rankin Scale at three months, early neurological improvement at 24 h, intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and mortality at three months between all dose tiers of tenecteplase and alteplase. RESULTS: Three relevant studies (Haley et al., Parsons et al., and ATTEST) included 291 patients and investigated three doses of tenecteplase (0.1, 0.25, 0.4 mg/kg). There were no differences between any dose of tenecteplase and alteplase for either efficacy or safety end points. Tenecteplase 0.25 mg/kg had the greatest odds to achieve early neurological improvement (OR [95%CI] 3.3 [1.5, 7.2], p = 0.093), excellent functional outcome (modified Rankin Scale 0-1) at three months (OR [95%CI] 1.9 [0.8, 4.4], p = 0.28), with reduced odds of intracerebral hemorrhage (OR [95%CI] 0.6 [0.2, 1.8], P = 0.43) compared with alteplase. Only 19 patients were treated with tenecteplase 0.4 mg/kg, which showed increased odds of symptomatic intracerebral hemorrhage compared with alteplase (OR [95% CI] 6.2 [0.7, 56.3]). CONCLUSIONS: While no significant differences between tenecteplase and alteplase were found, point estimates suggest potentially greater efficacy of 0.25 and 0.1 mg/kg doses with no difference in symptomatic intracerebral hemorrhage, and potentially higher symptomatic intracerebral hemorrhage risk with the 0.4 mg/kg dose. Further investigation of 0.25 mg/kg tenecteplase is warranted.
BACKGROUND: Tenecteplase, a modified plasminogen activator with higher fibrin specificity and longer half-life, may have advantages over alteplase in acute ischemic stroke thrombolysis. AIMS: We undertook an individual patient data meta-analysis of randomized controlled trials that compared alteplase with tenecteplase in acute stroke. METHODS: Eligible studies were identified by a MEDLINE search, and individual patient data were acquired. We compared clinical outcomes including modified Rankin Scale at three months, early neurological improvement at 24 h, intracerebral hemorrhage, symptomatic intracerebral hemorrhage, and mortality at three months between all dose tiers of tenecteplase and alteplase. RESULTS: Three relevant studies (Haley et al., Parsons et al., and ATTEST) included 291 patients and investigated three doses of tenecteplase (0.1, 0.25, 0.4 mg/kg). There were no differences between any dose of tenecteplase and alteplase for either efficacy or safety end points. Tenecteplase 0.25 mg/kg had the greatest odds to achieve early neurological improvement (OR [95%CI] 3.3 [1.5, 7.2], p = 0.093), excellent functional outcome (modified Rankin Scale 0-1) at three months (OR [95%CI] 1.9 [0.8, 4.4], p = 0.28), with reduced odds of intracerebral hemorrhage (OR [95%CI] 0.6 [0.2, 1.8], P = 0.43) compared with alteplase. Only 19 patients were treated with tenecteplase 0.4 mg/kg, which showed increased odds of symptomatic intracerebral hemorrhage compared with alteplase (OR [95% CI] 6.2 [0.7, 56.3]). CONCLUSIONS: While no significant differences between tenecteplase and alteplase were found, point estimates suggest potentially greater efficacy of 0.25 and 0.1 mg/kg doses with no difference in symptomatic intracerebral hemorrhage, and potentially higher symptomatic intracerebral hemorrhage risk with the 0.4 mg/kg dose. Further investigation of 0.25 mg/kg tenecteplase is warranted.
Authors: Babikir Kheiri; Mohammed Osman; Ahmed Abdalla; Tarek Haykal; Sahar Ahmed; Mustafa Hassan; Ghassan Bachuwa; Mohammed Al Qasmi; Deepak L Bhatt Journal: J Thromb Thrombolysis Date: 2018-11 Impact factor: 2.300
Authors: Bruce C V Campbell; Peter J Mitchell; Leonid Churilov; Nawaf Yassi; Timothy J Kleinig; Richard J Dowling; Bernard Yan; Steven J Bush; Vincent Thijs; Rebecca Scroop; Marion Simpson; Mark Brooks; Hamed Asadi; Teddy Y Wu; Darshan G Shah; Tissa Wijeratne; Henry Zhao; Fana Alemseged; Felix Ng; Peter Bailey; Henry Rice; Laetitia de Villiers; Helen M Dewey; Philip M C Choi; Helen Brown; Kendal Redmond; David Leggett; John N Fink; Wayne Collecutt; Thomas Kraemer; Martin Krause; Dennis Cordato; Deborah Field; Henry Ma; Bill O'Brien; Benjamin Clissold; Ferdinand Miteff; Anna Clissold; Geoffrey C Cloud; Leslie E Bolitho; Luke Bonavia; Arup Bhattacharya; Alistair Wright; Abul Mamun; Fintan O'Rourke; John Worthington; Andrew A Wong; Christopher R Levi; Christopher F Bladin; Gagan Sharma; Patricia M Desmond; Mark W Parsons; Geoffrey A Donnan; Stephen M Davis Journal: JAMA Date: 2020-04-07 Impact factor: 56.272