Outcomes in Antiplatelet‐Associated Intracerebral Hemorrhage in the TICH‐2 Randomized Controlled Trial

Author:

Law Zhe Kang12ORCID,Desborough Michael3ORCID,Roberts Ian4ORCID,Al‐Shahi Salman Rustam5ORCID,England Timothy J.6ORCID,Werring David J.7ORCID,Robinson Thompson8ORCID,Krishnan Kailash9ORCID,Dineen Robert1011ORCID,Laska Ann Charlotte12ORCID,Peters Nils131415ORCID,Egea‐Guerrero Juan Jose16ORCID,Karlinski Michal17ORCID,Christensen Hanne18ORCID,Roffe Christine19ORCID,Bereczki Daniel20ORCID,Ozturk Serefnur21ORCID,Thanabalan Jegan22ORCID,Collins Rónán23,Beridze Maia24ORCID,Bath Philip M.19ORCID,Sprigg Nikola19ORCID

Affiliation:

1. Stroke Trials Unit Division of Clinical Neuroscience University of Nottingham United Kingdom

2. Department of Medicine National University of Malaysia Kuala Lumpur Malaysia

3. Haemophilia and Thrombosis Centre Guy’s and St Thomas’ NHS Foundation Trust London United Kingdom

4. Clinical Trials Unit London School of Hygiene & Tropical Medicine London United Kingdom

5. Centre for Clinical Brain Sciences University of Edinburgh United Kingdom

6. Vascular Medicine Division of Medical Sciences & GEM Royal Derby Hospital CentreUniversity of Nottingham United Kingdom

7. Stroke Research Centre UCL Queen Square Institute of Neurology London United Kingdom

8. Department of Cardiovascular Sciences and National Institute for Health Research Biomedical Research Centre University of Leicester United Kingdom

9. Nottingham University Hospitals NHS Trust Nottingham United Kingdom

10. Radiological Sciences University of Nottingham United Kingdom

11. National Institute for Health Research Nottingham Biomedical Research Centre Nottingham United Kingdom

12. Department of Clinical Sciences Karolinska InstitutetDanderyd Hospital Sweden

13. Neurology and Stroke Center Klinik Hirslanden Zürich Switzerland

14. Neurology and Neurorehabilitation Unit University Center for Medicine of Aging Felix Platter‐Hospital Basel Switzerland

15. Department of Neurology and Stroke Center University Hospital Basel and University of Basel Switzerland

16. NeuroCritical Care Unit Virgen del Rocio University Hospital Seville Spain

17. Institute of Psychiatry and Neurology Warsaw Poland

18. Department of Neurology Bispebjerg Hospital and University of Copenhagen Denmark

19. Stroke Research Faculty of Medicine and Health Sciences Keele University Stoke‐on‐Trent United Kingdom

20. Department of Neurology Semmelweis University Budapest Hungary

21. Department of Neurology Selcuk University Faculty of Medicine Konya Turkey

22. Division of Neurosurgery Department of Surgery National University of Malaysia Kuala Lumpur Malaysia

23. Tallaght University Hospital Dublin Republic of Ireland

24. The First University Clinic of Tbilisi State Medical University Tbilisi Georgia

Abstract

Background Antiplatelet therapy increases the risk of hematoma expansion in intracerebral hemorrhage (ICH) while the effect on functional outcome is uncertain. Methods and Results This is an exploratory analysis of the TICH‐2 (Tranexamic Acid in Intracerebral Hemorrhage‐2) double‐blind, randomized, placebo‐controlled trial, which studied the efficacy of tranexamic acid in patients with spontaneous ICH within 8 hours of onset. Multivariable logistic regression and ordinal regression were performed to explore the relationship between pre‐ICH antiplatelet therapy, and 24‐hour hematoma expansion and day 90 modified Rankin Scale score, as well as the effect of tranexamic acid. Of 2325 patients, 611 (26.3%) had pre‐ICH antiplatelet therapy. They were older (mean age, 75.7 versus 66.5 years), more likely to have ischemic heart disease (25.4% versus 2.7%), ischemic stroke (36.2% versus 6.3%), intraventricular hemorrhage (40.2% versus 27.5%), and larger baseline hematoma volume (mean, 28.1 versus 22.6 mL) than the no‐antiplatelet group. Pre‐ICH antiplatelet therapy was associated with a significantly increased risk of hematoma expansion (adjusted odds ratio [OR], 1.28; 95% CI, 1.01–1.63), a shift toward unfavorable outcome in modified Rankin Scale (adjusted common OR, 1.58; 95% CI, 1.32–1.91) and a higher risk of death at day 90 (adjusted OR, 1.63; 95% CI, 1.25–2.11). Tranexamic acid reduced the risk of hematoma expansion in the overall patients with ICH (adjusted OR, 0.76; 95% CI, 0.62–0.93) and antiplatelet subgroup (adjusted OR, 0.61; 95% CI, 0.41–0.91) with no significant interaction between pre‐ICH antiplatelet therapy and tranexamic acid (P interaction=0.248). Conclusions Antiplatelet therapy is independently associated with hematoma expansion and unfavorable functional outcome. Tranexamic acid reduced hematoma expansion regardless of prior antiplatelet therapy use. Registration URL: https://www.isrctn.com ; Unique identifier: ISRCTN93732214.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Cardiology and Cardiovascular Medicine

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