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

Mair, Grant; von Kummer, Rüdiger; Morris, Zoe; von Heijne, Anders; Bradey, Nick; Cala, Lesley; Peeters, André; Farrall, Andrew J; Adami, Alessandro and Potter, Gillian, et al. (2016) In Neurology 86(2). p.25-118
Abstract

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... (More)

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.

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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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Neurology
volume
86
issue
2
pages
8 pages
publisher
American Academy of Neurology
external identifiers
  • scopus:84954342168
ISSN
1526-632X
DOI
10.1212/WNL.0000000000002236
language
English
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636f7e75-ccb2-4e4b-be7c-c940ff251f89
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2017-08-14 11:43:34
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2017-11-19 04:42:24
@article{636f7e75-ccb2-4e4b-be7c-c940ff251f89,
  abstract     = {<p>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).</p><p>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).</p><p>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 &lt; 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).</p><p>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.</p><p>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.</p>},
  author       = {Mair, Grant and von Kummer, Rüdiger and Morris, Zoe and von Heijne, Anders and Bradey, Nick and Cala, Lesley and Peeters, André and Farrall, Andrew J and Adami, Alessandro and Potter, Gillian and Cohen, Geoff and Sandercock, Peter A G and Lindley, Richard I. and Wardlaw, Joanna M. and ,  and Cronberg, Tobias},
  issn         = {1526-632X},
  keyword      = {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},
  language     = {eng},
  month        = {01},
  number       = {2},
  pages        = {25--118},
  publisher    = {American Academy of Neurology},
  series       = {Neurology},
  title        = {Effect of alteplase on the CT hyperdense artery sign and outcome after ischemic stroke},
  url          = {http://dx.doi.org/10.1212/WNL.0000000000002236},
  volume       = {86},
  year         = {2016},
}