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

Research output: Contribution to journalArticlepeer-review


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)118-25
Number of pages8
Issue number2
Publication statusPublished - 2016 Jan 12
Externally publishedYes

Free 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


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