Does pre-injury clopidogrel use increase the risk of intracranial haemorrhage post head injury in adult patients? A systematic review and meta-analysis.

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 I of 75%. Sensitivity analysis produced an I 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.