Impact of computed tomography perfusion imaging on the response to tenecteplase in ischemic stroke: analysis of two randomized controlled trials

Bivard, A. et al. (2017) Impact of computed tomography perfusion imaging on the response to tenecteplase in ischemic stroke: analysis of two randomized controlled trials. Circulation, 135(5), pp. 440-448. (doi: 10.1161/CIRCULATIONAHA.116.022582) (PMID:27965285)

Abstract

Background: We pooled 2 clinical trials of tenecteplase compared with alteplase for the treatment of acute ischemic stroke, 1 that demonstrated superiority of tenecteplase and the other that showed no difference between the treatments in patient clinical outcomes. We tested the hypotheses that reperfusion therapy with tenecteplase would be superior to alteplase in improving functional outcomes in the group of patients with target mismatch as identified with advanced imaging. Methods: We investigated whether tenecteplase-treated patients had a different 24-hour reduction in the National Institutes of Health Stroke Scale and a favorable odds ratio of a modified Rankin scale score of 0 to 1 versus 2 to 6 compared with alteplase-treated patients using linear regression to generate odds ratios. Imaging outcomes included rates of vessel recanalization and infarct growth at 24 hours and occurrence of large parenchymal hematoma. Baseline computed tomography perfusion was analyzed to assess whether patients met the target mismatch criteria (absolute mismatch volume >15 mL, mismatch ratio >1.8, baseline ischemic core <70 mL, and volume of severely hypoperfused tissue <100 mL). Patients meeting target mismatch criteria were analyzed as a subgroup to identify whether they had different treatment responses from the pooled group. Results: Of 146 pooled patients, 71 received alteplase and 75 received tenecteplase. Tenecteplase-treated patients had greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 7; alteplase, 2; P=0.018) and less parenchymal hematoma (2 of 75 versus 10 of 71; P=0.02). The pooled group did not show improved patient outcomes when treated with tenecteplase (modified Rankin scale score 0–1: odds ratio, 1.77; 95% confidence interval, 0.89–3.51; P=0.102) compared with alteplase therapy. However, in patients with target mismatch (33 tenecteplase, 35 alteplase), treatment with tenecteplase was associated with greater early clinical improvement (median National Institutes of Health Stroke Scale score change: tenecteplase, 6; alteplase, 1; P<0.001) and better late independent recovery (modified Rankin scale score 0–1: odds ratio, 2.33; 95% confidence interval, 1.13–5.94; P=0.032) than those treated with alteplase. Conclusions: Tenecteplase may offer an improved efficacy and safety profile compared with alteplase, benefits possibly exaggerated in patients with baseline computed tomography perfusion–defined target mismatch. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01472926. URL: https://www.anzctr.org.au. Unique identifier: ACTRN12608000466347.

• Item Type: Articles
• Additional Information: The Australian-TNK study was funded by the National Health and Medical Research Council. The ATTEST study was funded by the UK Stroke Association.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Cheripelli, Dr Bharath Kumar and Huang, Dr Xuya and Muir, Professor Keith and Ford, Professor Ian and Kalladka, Dr Dheeraj and Moreton, Dr Fiona
• Authors: Bivard, A., Huang, X., McElduff, P., Levi, C. R., Campbell, B. C.V., Cheripelli, B. K., Kalladka, D., Moreton, F. C., Ford, I., Bladin, C. F., Davis, S. M., Donnan, G. A., Muir, K. W., and Parsons, M. W.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre; College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
• Journal Name: Circulation
• Publisher: American Heart Association
• ISSN: 0009-7322
• ISSN (Online): 1524-4539
• Published Online: 13 December 2016
• Copyright Holders: Copyright © 2016 American Heart Association, Inc.
• First Published: First published in Circulation 135(5): 440-448
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher