• Xuya Huang, Rachael MacIsaac, John Lp Thompson, Bruce Levin, Richard Buchsbaum, E Clarke Haley, Christopher Levi, Bruce Campbell, Christopher Bladin, Mark Parsons, and Keith W Muir.
• Institute of Neuroscience and Psychology, University of Glasgow, Glasgow, UK.
• Int J Stroke. 2016 Jul 1; 11 (5): 534-43.

BackgroundTenecteplase, a modified plasminogen activator with higher fibrin specificity and longer half-life, may have advantages over alteplase in acute ischemic stroke thrombolysis.AimsWe undertook an individual patient data meta-analysis of randomized controlled trials that compared alteplase with tenecteplase in acute stroke.MethodsEligible 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.ResultsThree 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]).ConclusionsWhile 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.© 2016 World Stroke Organization.

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