Antiplatelet therapy and central nervous system hematomas: a cohort study using real-world data from the FAERS and VigiAccess databases

BACKGROUND: Antiplatelet therapy is a cornerstone in the management of atherosclerotic cardiovascular disease. However, the risk profile of central nervous system (CNS) hematomas associated with antiplatelet agents remains incompletely characterized. METHODS: We analyzed CNS-related hematoma adverse event (hAE) reports across the four antiplatelet drugs, using data from the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the World Health Organization's VigiAccess databases. Disproportionality analysis was conducted to identify positive signals. Stratified analysis assessed risk differentials by age and gender, time-to-onset analysis characterized temporal patterns, and a global assessment of the evidence was established. RESULTS: A total of 2274 CNS-related hAE reports were identified in FAERS and 7229 in VigiAccess. All four antiplatelet drugs demonstrated significant disproportionality signals, with clopidogrel [FAERS: reporting odds ratio (ROR), 26.79; VigiAccess: ROR: 36.69] and aspirin (FAERS: ROR, 22.06; VigiAccess: ROR, 40.13) showing the strongest associations, followed by prasugrel (FAERS: ROR, 16.91; VigiAccess: ROR, 24.02), and ticagrelor (FAERS: ROR, 8.07; VigiAccess: ROR, 9.80). Subdural hematomas were the most frequently reported subtype (FAERS: 63.11%; VigiAccess: 62.72%). Female patients exhibited stronger signals than males across all drugs. All antiplatelet drugs revealed early failure-type temporal profiles, with median onset times ranging from 12.0 days for ticagrelor to 442.5 days for aspirin ( P < 0.001). CONCLUSIONS: We found a disproportionately significant association between antiplatelet therapy and CNS-related hematomas, with distinct patterns observed across drug types, patient demographics, and temporal profiles. These findings provide critical insights to inform risk stratification, clinical decision-making, and safety monitoring in patients undergoing antiplatelet therapy.