Selection for delayed intravenous alteplase treatment based on a prognostic score

VISTA Collaboration and ECASS, ATLANTIS, NINDS, and EPITHET Investigators

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 4·5h after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection. Methods: 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 4·5-6h 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 4·5-6h, 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. Results: 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 4·5-6h 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. Conclusion: Selection of patients between 4·5 and 6h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.

Original languageEnglish (US)
Pages (from-to)90-94
Number of pages5
JournalInternational Journal of Stroke
Volume10
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

Fingerprint

Tissue Plasminogen Activator
Randomized Controlled Trials
Stroke
Odds Ratio
Patient Selection
Therapeutics
Hemorrhage
Mortality
National Institutes of Health (U.S.)
Research Design
Confidence Intervals
Population

Keywords

  • Analysis
  • Clinical trials
  • Outcomes
  • Prognostic score
  • Thrombolysis

ASJC Scopus subject areas

  • Neurology
  • Medicine(all)

Cite this

Selection for delayed intravenous alteplase treatment based on a prognostic score. / VISTA Collaboration and ECASS, ATLANTIS, NINDS, and EPITHET Investigators.

In: International Journal of Stroke, Vol. 10, No. 1, 01.01.2015, p. 90-94.

Research output: Contribution to journalArticle

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, vol. 10, no. 1, pp. 90-94. https://doi.org/10.1111/j.1747-4949.2012.00943.x
VISTA Collaboration and ECASS, ATLANTIS, NINDS, and EPITHET Investigators. / Selection for delayed intravenous alteplase treatment based on a prognostic score. In: International Journal of Stroke. 2015 ; Vol. 10, No. 1. pp. 90-94.
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T1 - Selection for delayed intravenous alteplase treatment based on a prognostic score

AU - VISTA Collaboration and ECASS, ATLANTIS, NINDS, and EPITHET Investigators

AU - Fulton, Rachael L.

AU - Lees, Kennedy R.

AU - Bluhmki, Erich

AU - Biegert, Gabriele

AU - Albers, Gregory W.

AU - Davis, Stephen M.

AU - Donnan, Geoffrey A.

AU - Grotta, James C.

AU - Hacke, Werner

AU - Kaste, Markku

AU - von Kummer, Rüdiger

AU - Shuaib, Ashfaq

AU - Toni, Danilo

AU - Alexandrov, A.

AU - Bath, P. W.

AU - Bluhmki, E.

AU - Claesson, L.

AU - Curram, J.

AU - Davis, S. M.

AU - Donnan, G.

AU - Diener, H. C.

AU - Fisher, M.

AU - Gregson, B.

AU - Grotta, J.

AU - Hacke, W.

AU - Hennerici, M. G.

AU - Hommel, M.

AU - Kaste, M.

AU - Lyden, K. R Lees P

AU - Marler, J.

AU - Muir, K.

AU - Sacco, Ralph L

AU - Shuaib, A.

AU - Teal, P.

AU - Wahlgren, N. G.

AU - Warach, S.

AU - Weimar, C.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 4·5h after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection. Methods: 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 4·5-6h 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 4·5-6h, 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. Results: 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 4·5-6h 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. Conclusion: Selection of patients between 4·5 and 6h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.

AB - 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 4·5h after stroke onset. We proposed prognostic scoring methods to identify a strategy for patient selection. Methods: 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 4·5-6h 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 4·5-6h, 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. Results: 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 4·5-6h 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. Conclusion: Selection of patients between 4·5 and 6h based on simple clinical measures failed to deliver a population in whom the alteplase effect would be safe and effective.

KW - Analysis

KW - Clinical trials

KW - Outcomes

KW - Prognostic score

KW - Thrombolysis

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