Pre-Injury Antiplatelet Therapy and Risk of Adverse Outcomes after Traumatic Brain Injury: A Systematic Review and Meta-Analysis

François Mathieu; Armaan K Malhotra; Jerry C Ku; Frederick A Zeiler; Jefferson R Wilson; Farhad Pirouzmand; Damon C Scales

doi:10.1089/neur.2022.0042

Pre-Injury Antiplatelet Therapy and Risk of Adverse Outcomes after Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Neurotrauma Rep. 2022 Aug 10;3(1):308-320. doi: 10.1089/neur.2022.0042. eCollection 2022.

Authors

François Mathieu^{1

2}, Armaan K Malhotra¹, Jerry C Ku¹, Frederick A Zeiler^{3

4

5

6

7}, Jefferson R Wilson^{1

8}, Farhad Pirouzmand^{1

9}, Damon C Scales^{2

10

11

12}

Affiliations

¹ Division of Neurosurgery, Department of Surgery, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
² Interdepartmental Division of Critical Care Medicine, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.
³ Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, Manitoba, Canada.
⁴ Section of Neurosurgery, Department of Surgery, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.
⁵ Biomedical Engineering, Faculty of Engineering, University of Manitoba, Winnipeg, Manitoba, Canada.
⁶ Centre on Aging, University of Manitoba, Winnipeg, Manitoba, Canada.
⁷ Division of Anaesthesia, Department of Medicine, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.
⁸ Department of Neurosurgery, St. Michael's Hospital, Toronto, Ontario, Canada.
⁹ Division of Neurosurgery, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
¹⁰ ICES, Toronto, Ontario, Canada.
¹¹ Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
¹² Institute of Health Policy, Management and Evaluation, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada.

Abstract

There is an increasing number of trauma patients presenting on pre-injury antiplatelet (AP) agents attributable to an aging population and expanding cardio- or cerebrovascular indications for antithrombotic therapy. The effects of different AP regimens on outcomes after traumatic brain injury (TBI) have yet to be elucidated, despite the implications on patient/family counseling and the potential need for better reversal strategies. The goal of this systematic review and meta-analysis was to assess the impact of different pre-injury AP regimens on outcomes after TBI. In accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the OVID Medline, Embase, BIOSIS, Scopus, and Cochrane databases were searched from inception to February 2022 using a combination of terms pertaining to TBI and use of AP agents. Baseline demographics and study characteristics as well as outcome data pertaining to intracerebral hematoma (ICH) progression, need for neurosurgical intervention, hospital length of stay, mortality, and functional outcome were extracted. Pooled odds ratios (ORs) and mean differences comparing groups were calculated using random-effects models. Thirteen observational studies, totaling 1244 patients receiving single AP therapy with acetylsalicylic acid or clopidogrel, 413 patients on dual AP therapy, and 3027 non-AP users were included. No randomized controlled trials were identified. There were significant associations between dual AP use and ICH progression (OR, 2.81; 95% confidence interval [CI], 1.19-6.61; I ², 85%; p = 0.02) and need for neurosurgical intervention post-TBI (OR, 1.61; 95% CI, 1.15-2.28; I ², 15%; p = 0.006) compared to non-users, but not between single AP therapy and non-users. There were no associations between AP use and hospital length of stay or mortality after trauma. Pre-injury dual AP use, but not single AP use, is associated with higher rates of ICH progression and neurosurgical intervention post-TBI. However, the overall quality of studies was low, and this association should be further investigated in larger studies.

Keywords: antiplatelet therapy; intracranial hemorrhage; mortality; traumatic brain injury.