Bleeding with intensive versus guideline antiplatelet therapy in acute cerebral ischaemia

Lisa J Woodhouse, Jason P Appleton, Hanne Christensen, Rob A Dineen, Timothy J England, Marilyn James, Kailash Krishnan, Alan A Montgomery, Anna Ranta, Thompson G Robinson, Nikola Sprigg, Philip M Bath

Abstract

Intensive antiplatelet therapy did not reduce recurrent stroke/transient ischaemic attack (TIA) events as compared with guideline treatment in the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial, but did increase the frequency and severity of bleeding. In this pre-specified analysis, we investigated predictors of bleeding and the association of bleeding with outcome. TARDIS was an international prospective randomised open-label blinded-endpoint trial in participants with ischaemic stroke or TIA within 48 h of onset. Participants were randomised to 30 days of intensive antiplatelet therapy (aspirin, clopidogrel, dipyridamole) or guideline-based therapy (either clopidogrel alone or combined aspirin and dipyridamole). Bleeding was defined using the International Society on Thrombosis and Haemostasis five-level ordered categorical scale: fatal, major, moderate, minor, none. Of 3,096 participants, bleeding severity was: fatal 0.4%, major 1.5%, moderate 1.2%, minor 11.4%, none 85.5%. Major/fatal bleeding was increased with intensive as compared with guideline therapy: 39 vs. 17 participants, adjusted hazard ratio 2.21, 95% CI 1.24-3.93, p = 0.007. Bleeding events diverged between treatment groups in the 8-35 day period but not in the 0-7 or 36-90 day epochs. In multivariate analysis more, and more severe, bleeding events were seen with increasing age, female sex, pre-morbid dependency, increased time to randomisation, prior major bleed, prior antiplatelet therapy and in those randomised to triple vs guideline antiplatelet therapy. More severe bleeding was associated with worse clinical outcomes across multiple physical, emotional and quality of life domains.Trial registration ISRCTN47823388 .

Original languageEnglish
Article number11717
JournalScientific Reports
Volume13
Issue number1
Pages (from-to)11717
ISSN2045-2322
DOIs
Publication statusPublished - 20 Jul 2023

Keywords

  • Female
  • Humans
  • Platelet Aggregation Inhibitors/adverse effects
  • Brain Ischemia/drug therapy
  • Ischemic Attack, Transient/drug therapy
  • Clopidogrel/therapeutic use
  • Stroke/drug therapy
  • Prospective Studies
  • Quality of Life
  • Aspirin/adverse effects
  • Hemorrhage/drug therapy
  • Dipyridamole/therapeutic use
  • Drug Therapy, Combination
  • Ischemic Stroke/drug therapy
  • Acute Disease

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