The association of opioid use disorder with post-cerebral aneurysm rupture outcomes

BACKGROUND: Opioid use disorder (OUD) is common among adults with cerebrovascular disease, but its association with outcomes after cerebral aneurysm rupture (CAR) and the role of medications for OUD (MOUD) are poorly characterized. METHODS: Using Oracle Health Real-World Data™, we assembled a cohort of patients with CAR (2000-2025), identified using a prespecified EHR phenotype based on hemorrhage diagnosis codes, aneurysm-related diagnosis/procedure codes, and exclusion criteria. The primary exposure was pre-existing OUD; secondary analyses compared patients with OUD who did versus did not receive MOUD before rupture. Outcomes included epilepsy/seizures, hydrocephalus, myocardial infarction, death, length of stay (LOS), and 30-day readmission. Shared frailty Cox models estimated adjusted hazard ratios (aHRs) for time-to-event outcomes; mixed-effects log-linear regression estimated percent change in LOS. No clear association was observed for 30-day readmission (aHR 1.07, 95% CI 0.98-1.19). Among patients with OUD, MOUD-related analyses were exploratory; hydrocephalus and 30-day readmission showed nominally lower hazards before multiplicity adjustment but did not remain significant after false discovery rate correction. CONCLUSIONS: Pre-existing OUD was associated with higher post-rupture mortality, seizures, myocardial infarction, and longer hospitalization. Further studies are needed to clarify mechanisms, better address residual confounding, and determine whether these associations persist across settings.