VISTA Steering committee members: A. Alexandrov, P.W. Bath, E. Bluhmki, L Claesson, J. Curram, S.M Davis, G. Donnan, H. C. Diener, M. Fisher, B. Gregson, J. Grotta, W. Hacke, M.G. Hennerici, M. Hommel, M. Kaste, K.R. Lees P. Lyden, J. Marler, K. Muir, R. Sacco, A. Shuaib, P. Teal, N.G. Wahlgren, S. Warach, and C. Weimar.
Selection for delayed intravenous alteplase treatment based on a prognostic score
Article first published online: 7 JAN 2013
© 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization
International Journal of Stroke
Volume 10, Issue 1, pages 90–94, January 2015
How to Cite
Fulton, R. L., Lees, K. R., Bluhmki, E., Biegert, G., Albers, G. W., Davis, S. M., Donnan, G. A., Grotta, J. C., Hacke, W., Kaste, M., von Kummer, R., Shuaib, A., Toni, D. and VISTA Collaboration and ECASS, ATLANTIS, NINDS, and EPITHET Investigators (2015), Selection for delayed intravenous alteplase treatment based on a prognostic score. International Journal of Stroke, 10: 90–94. doi: 10.1111/j.1747-4949.2012.00943.x
Subject Codes: Thrombolysis.
Conflicts of interest: None declared.
- Issue published online: 10 DEC 2014
- Article first published online: 7 JAN 2013
- Manuscript Accepted: 14 JUN 2012
- Manuscript Received: 16 FEB 2012
- clinical trials;
- prognostic score;
Background and Purpose
Approved use of intravenous alteplase for ischemic stroke offers net benefit. Pooled randomized controlled trial analysis suggests additional patients could benefit but others be harmed with treatment initiated beyond 4·5 h after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection.
We selected 500 patients treated by intravenous alteplase and 500 controls from Virtual International Stroke Trials Archive, matching modified Rankin score outcomes to those from pooled randomized controlled trial 4·5–6 h data. We ranked patients by prognostic score. We chose limits to optimize our sample for a net treatment benefit significant at P = 0·01 by Cochran–Mantel–Haenszel test and by ordinal regression. For validation, we had these applied to the pooled randomized controlled trial data for 4·5–6 h, testing for net benefit by Cochran–Mantel–Haenszel test, ordinal regression, and also by dichotomized outcomes: modified Rankin score 0–1, mortality and parenchymal hemorrhage type 2 bleeds. All analyses were adjusted for age and National Institutes of Health Stroke Scale.
In the training dataset, limits of 56–95 on a prognostic score retained 714 patients in whom there was net benefit significant at P = 0·01. When applied to the 1120 patients in the pooled randomized controlled trial 4·5–6 h dataset, score limits of 56–95 retained 711 patients and gave odds ratio for improved modified Rankin score distribution of 1·13, 95% confidence interval 0·87–1·47, Cochran–Mantel–Haenszel P = 0·89. More patients achieved modified Rankin score 0–1 (odds ratio 1·44, 1·02–2·05, P = 0·04) but mortality and parenchymal hemorrhage type 2 bleeds were increased: odds ratio 1·56, 1·01–2·40, P = 0·04; odds ratio 15·6, 3·7–65·8, P = 0·0002, respectively.
Selection of patients between 4·5 and 6 h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.