Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke

Grant Mair, Rüdiger von Kummer, Zoe Morris, Anders von Heijne, Nick Bradey, Lesley Cala, André Peeters, Andrew J Farrall, Alessandro Adami, Gillian Potter, Geoff Cohen, Peter A. G. Sandercock, Richard I. Lindley, Joanna M. Wardlaw, IST-3 Collaborative Group

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Objective: To investigate whether the location and extent of the CT hyperdense artery sign (HAS) at presentation affects response to IV alteplase in the randomized controlled Third International Stroke Trial (IST-3).

Methods: All prerandomization and follow-up (24–48 hours) CT brain scans in IST-3 were assessed for HAS presence, location, and extent by masked raters. We assessed whether HAS grew, persisted, shrank, or disappeared at follow-up, the association with 6-month functional outcome, and effect of alteplase. IST-3 is registered (ISRCTN25765518).

Results: HAS presence (vs absence) independently predicted poor 6-month outcome (increased Oxford Handicap Scale [OHS]) on adjusted ordinal regression analysis (odds ratio [OR] 0.66, p < 0.001). Outcome was worse in patients with more (vs less) extensive HAS (OR 0.61, p = 0.027) but not in proximal (vs distal) HAS (p = 0.420). Increasing age was associated with more HAS growth at follow-up (OR 1.01, p = 0.013). Treatment with alteplase increased HAS shrinkage/disappearance at follow-up (OR 0.77, p = 0.006). There was no significant difference in HAS shrinkage with alteplase in proximal (vs distal) or more (vs less) extensive HAS (p = 0.516 and p = 0.580, respectively). There was no interaction between presence vs absence of HAS and benefit of alteplase on 6-month OHS (p = 0.167).

Conclusions: IV alteplase promotes measurable reduction in HAS regardless of HAS location or extent. Alteplase increased independence at 6 months in patients with and without HAS.

Classification of evidence: This study provides Class I evidence that for patients within 6 hours of ischemic stroke with a CT hyperdense artery sign, IV alteplase reduced intra-arterial hyperdense thrombus.

Original languageEnglish
Pages (from-to)118-125
Number of pages8
Issue number2
Early online date9 Dec 2015
Publication statusPublished - 12 Jan 2016

Bibliographical note

© 2015 American Academy of Neurology.

The startup phase of IST-3 was supported by a grant from the Stroke Association, UK (TSA 04/99). The expansion phase was funded by the Health Foundation UK (2268/1282). The scan reading development was funded by Chest, Heart Stroke Scotland (R100/7). The main phase of the trial is funded by UK Medical Research Council (MRC) (grant numbers G0400069 and EME 09-800-15) and managed by NIHR on behalf of the MRC-NIHR partnership; the Research Council of Norway; Arbetsmarknadens Partners Forsakringsbolag (AFA) Insurances Sweden; the Swedish Heart Lung Fund; The Foundation of Marianne and Marcus Wallenberg, Stockholm County Council; Karolinska Institute Joint ALF-project grants Sweden; the Polish Ministry of Science and Education (grant number 2PO5B10928); the Australian Heart Foundation; Australian National Health and Medical Research Council (NHMRC); the Swiss National Research Foundation; the Swiss Heart Foundation; the Foundation for Health and Cardio-/Neurovascular Research, Basel, Switzerland; the Assessorato alla Sanita, Regione dell'Umbria, Italy; and, Danube University, Krems, Austria. Boehringer-Ingelheim GmbH donated drug and placebo for the 300 patients in the double-blind phase, but thereafter had no role in the trial. The UK Stroke Research Network (SRN study ID 2135) adopted the trial on 1/5/2006, supported the initiation of new UK sites, and in some centers, and, after that date, data collection was undertaken by staff funded by the network or working for associated NHS organizations. IST-3 acknowledges the support of the NIHR Stroke Research Network, NHS Research Scotland (NRS), through the Scottish Stroke Research Network, and the National Institute for Social Care and Health Research Clinical Research Centre (NISCHR CRC). The central imaging work was undertaken at the Brain Imaging Research Centre (www.sbirc.ed.ac.uk), a member of the Scottish Imaging Network: A Platform for Scientific Excellence (SINAPSE) collaboration (www.sinapse.ac.uk), at the Division of Clinical Neurosciences, University of Edinburgh. SINAPSE is funded by the Scottish Funding Council (SFC) and the Chief Scientist Office of the Scottish Executive (CSO). Additional support was received from Chest Heart and Stroke Scotland, DesAcc, University of Edinburgh, Danderyd Hospital R&D Department, Karolinska Institutet, Oslo University Hospital, and the Dalhousie University Internal Medicine Research Fund.


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