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Original research
Prior antiplatelet therapy and haematoma expansion after primary intracerebral haemorrhage: an individual patient-level analysis of CLEAR III, MISTIE III and VISTA-ICH
  1. Santosh Murthy1,
  2. David J Roh2,
  3. Abhinaba Chatterjee1,
  4. Nichol McBee3,
  5. Neal S Parikh1,
  6. Alexander E Merkler1,
  7. Babak B Navi1,
  8. Guido J Falcone4,
  9. Kevin N Sheth4,
  10. Issam Awad5,
  11. Daniel Hanley6,
  12. Hooman Kamel1,
  13. Wendy C Ziai7
  14. CLEAR III, MISTIE III and VISTA-ICH Collaborators
  1. 1Clinical and Translational Neuroscience Unit, Feil Family Brain and Mind Research Institute and Department of Neurolgy, Weill Cornell Medicine, New York, NY, United States
  2. 2Neurology, Columbia University Irving Medical Center, New York, New York, USA
  3. 3Neurology, Johns Hopkins University, Baltimore, Maryland, USA
  4. 4Division of Neurocritical Care and Emergency Neurology, Yale University School of Medicine, New Haven, Connecticut, USA
  5. 5Neurosurgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA
  6. 6Division of Brain Injury Outcomes, Johns Hopkins University, Baltimore, Maryland, USA
  7. 7Departments of Neurology, Neurosurgery, and Anesthesiology Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States
  1. Correspondence to Dr Santosh Murthy, Department of Neurology, Weill Cornell Medicine, New York, New York 10065, USA; sam9200{at}med.cornell.edu

Abstract

Objective To evaluate the relationship between prior antiplatelet therapy (APT) and outcomes after primary intracerebral haemorrhage (ICH), and assess if it varies by haematoma location.

Methods We pooled individual patient data from the Virtual International Stroke Trials Archive-ICH trials dataset, Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage III trial and the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation Phase III trial. The exposure was APT preceding ICH diagnosis. The primary outcome was haematoma expansion at 72 hours. Secondary outcomes were admission haematoma volume, all-cause mortality, death or major disability (modified Rankin Scale (mRS) score ≥4) and shift in mRS distribution. Mixed-effects models were used to assess the relationship between APT and outcomes. Secondary analyses were stratified by ICH location and study cohort.

Results Among 1420 patients with ICH, there were 782 (55.1%) lobar and 596 (42.0%) deep haemorrhages. APT was reported in 284 (20.0%) patients. In adjusted regression models, prior APT was not associated with haematoma expansion (OR, 0.97; 95% CI 0.60 to 1.57), major disability or death (OR, 1.05; 95% CI 0.61 to 1.63), all-cause mortality (OR, 0.89; 95% CI 0.47 to 1.85), admission haematoma volume (beta, −0.17; SE, 0.09; p=0.07) and shift in mRS (p=0.43). In secondary analyses, APT was associated with admission haematoma volume in lobar ICH (beta, 0.25; SE, 0.12; p=0.03), but there was no relationship with other ICH outcomes when stratified by haematoma location or study cohort.

Conclusions In a large heterogeneous cohort of patients with ICH, prior APT was not associated with haematoma expansion or functional outcomes after ICH, regardless of haematoma location. APT was associated with admission haematoma volumes in lobar ICH.

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Footnotes

  • Twitter @san_murthy

  • Contributors SM: study concept, design, acquisition and interpretation of data, drafting of manuscript with critical revisions. SM had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. DJR: critical revision of the manuscript for intellectual content. AC: critical revision of the manuscript for intellectual content. MC: critical revision of the manuscript for intellectual content. NM: critical revision of the manuscript for intellectual content. NSP: critical revision of the manuscript for intellectual content. AEM: critical revision of the manuscript for intellectual content. BBN: critical revision of the manuscript for intellectual content. GJF: critical revision of the manuscript for intellectual content. KNS: critical revision of the manuscript for intellectual content. IA: critical revision of the manuscript for intellectual content. DH: critical revision of the manuscript for intellectual content. HK: critical revision of the manuscript for intellectual content. WCZ: study concept, design, acquisition and analysis of data, drafting of the manuscript including critical revisions for intellectual content and study supervision.

  • Funding The study was funded by the National Institutes of Health grants (K23NS105948) to SBM, and (U01-NS08082 and U01-NS080824) to DH and WCZ.

  • Competing interests BBN is supported by the NIH (K23NS091395) and the Florence Gould Endowment for Discovery in Stroke, serves as a member of the data and safety monitoring board for the PCORI-funded TRAVERSE trial and has received personal fees for medicolegal consulting on stroke. AEM is supported by AHA grant 18CDA34110419 and the Leon Levy Foundation. He has received personal fees for medicolegal consulting on stroke. GJF is supported by the NIH (K76AG059992, R03NS112859), the American Heart Association (18IDDG34280056) and the Yale Pepper Scholar Award (P30AG021342). KNS is supported by the NIH (U24NS107215, U24NS107136, RO1NR018335, and U01NS106513), Novartis, and Bard, and reports grants from Hyperfine, Biogen, and Astrocyte unrelated to this work. DH is supported by the NIH (U01NS080824 and U24TR001609), and reports personal fees from Op2Lysis, personal fees from BrainScope and Neurotrope, and non-financial support from Genentech outside the submitted work. HK is supported by the NIH (U01NS095869 and R01NS097443) and the Michael Goldberg Research Fund; serves as the co-PI for the NIH-funded ARCADIA trial which receives in-kind study drug from the BMS-Pfizer Alliance and in-kind study assays from Roche Diagnostics; serves as a steering committee member of Medtronic’s Stroke AF trial (uncompensated); serves on an endpoint adjudication committee for a trial of empagliflozin for Boehringer-Ingelheim; and has served on an advisory board for Roivant Sciences related to Factor XI inhibition. WCZ receives consulting fees from C.R. Bard, Inc. outside of the area of work commented on here. All remaining authors declare no competing interests.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request. Individual de-identified participant data from the VISTA-ICH, CLEAR III and MISTIE III may be obtained by submitting a formal proposal to the respective steering committees. Additionally, data from the CLEAR III and MISTIE III trials may be requested by writing to the National Institute of Neurological Disorders and Stroke clinical trials repository.

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