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Does pre-injury clopidogrel use increase the risk of intracranial haemorrhage post head injury in adult patients? A systematic review and meta-analysis
  1. Samuel Moffatt1,2,
  2. Sara Venturini3,
  3. Paul Vulliamy4
  1. 1 Emergency Department, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UK
  2. 2 Queen Mary University of London, London, UK
  3. 3 Department of Neurosciences, Cambridge University, Cambridge, UK
  4. 4 Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
  1. Correspondence to Dr Samuel Moffatt, Emergency Department, University Hospitals Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, UK; sammoffatt{at}


Background Several current guidelines do not include antiplatelet use as an explicit indication for CT scan of the head following head injury. The impact of individual antiplatelet agent use on rates of intracranial haemorrhage is unclear. The primary objective of this systematic review was to assess if clopidogrel monotherapy was associated with traumatic intracranial haemorrhage (tICH) on CT of the head within 24 hours of presentation following head trauma compared with no antithrombotic controls.

Methods Eligible studies were non-randomised studies with participants aged ≥18 years old with head injury. Studies had to have conducted CT of the head within 24 hours of presentation and contain a no antithrombotic control group and a clopidogrel monotherapy group.

Eight databases were searched from inception to December 2020. Assessment of identified studies against inclusion criteria and data extraction were carried out independently and in duplicate by two authors.

Quality assessment and risk of bias (ROB) were assessed using the Newcastle–Ottawa Quality Assessment tool and Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. Meta-analysis was conducted using a random-effects model and reported as an OR and 95% CI.

Results Seven studies were eligible for inclusion with a total of 21 898 participants that were incorporated into the meta-analysis. Five studies were retrospective. Clopidogrel monotherapy was not significantly associated with an increase in risk of tICH compared with no antithrombotic controls (OR 0.97, 95% CI 0.54 to 1.75). Heterogeneity was high with an I2 of 75%. Sensitivity analysis produced an I2 of 21% and did not show a significant association between clopidogrel monotherapy and risk of tICH (OR 1.16, 95% CI 0.87 to 1.55). All studies scored for moderate to serious ROB on categories in the ROBINS-I tool.

Conclusion Included studies were vulnerable to confounding and several were small-scale studies. The results should be interpreted with caution given the ROB identified. This study does not provide statistically significant evidence that clopidogrel monotherapy patients are at increased risk of tICH after head injury compared with no antithrombotic controls.

PROSPERO registration number CRD42020223541.

  • emergency department
  • Computed Tomography
  • craniocerebral trauma

Data availability statement

Data are available in a public, open access repository.

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Data availability statement

Data are available in a public, open access repository.

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  • Handling editor Edward Carlton

  • Contributors SM designed and led this systematic review and meta-analysis and carried out the search, data extraction, data analysis and wrote the paper. SV conducted independent duplicate assessment of the identified studies against the inclusion criteria and independently duplicated data extraction. PV was project supervisor for this systematic review and meta-analysis. SM is the guarantor for this paper and accepts full responsibility for the conduct of the study.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

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

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.