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

Research output: Contribution to journalArticle


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.


  • 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
External organisations
  • Västmanland Hospital
Research areas and keywords


  • Aged, Aged, 80 and over, Arteries, Brain Ischemia, Female, Fibrinolytic Agents, Follow-Up Studies, Humans, Male, Stroke, Tissue Plasminogen Activator, Tomography, X-Ray Computed, Treatment Outcome, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't
Original languageEnglish
Pages (from-to)118-25
Number of pages8
Issue number2
Publication statusPublished - 2016 Jan 12
Publication categoryResearch
Externally publishedYes