Materials and methods

Study design and data source

This retrospective cohort study was conducted using the TriNetX Global Collaborative Network, a federated database containing de-identified electronic health records from over 170 healthcare organizations. The network includes data on patient demographics, diagnoses, procedures, medications, and healthcare utilization collected from participating institutions in real time.

Cohort selection

Adult patients (≥18 years) with a diagnosis of nontraumatic intracerebral hemorrhage (ICD-10 code I61) were identified [6]. Patients with traumatic intracranial injury were excluded.

Patients were stratified into two cohorts based on documented statin prescriptions within three months prior to the index hemorrhage event. The statin cohort included patients with documented prescriptions for statins, including atorvastatin, simvastatin, or rosuvastatin. The non-statin cohort included patients without documented statin prescriptions during this period. Because TriNetX records prescription data rather than pharmacy dispensing or medication adherence, treatment exposure was defined by documented prescription history, and actual medication adherence or persistence could not be confirmed.

Propensity score matching

One-to-one propensity score matching was performed to reduce measured confounding. Covariates included age, sex, race, and comorbidities such as hypertension, diabetes mellitus, atrial fibrillation, chronic kidney disease, and cardiovascular disease, as well as concurrent use of anticoagulant and antiplatelet medications.

After matching, balanced cohorts of 82,755 patients in each group were achieved. Standardized mean differences were less than 0.1 for all included variables, indicating adequate balance between cohorts. Clinical and radiographic variables including admission neurological severity (e.g., Glasgow Coma Scale and NIH Stroke Scale scores), hematoma volume, hemorrhage location, intraventricular extension, hematoma expansion, and ICH score were not available within the TriNetX database and therefore could not be incorporated into the matching process.

Outcomes

Outcomes were assessed within 30 days of the index intracerebral hemorrhage event. The primary outcome was all-cause mortality. Secondary outcomes included craniotomy or cerebrospinal fluid diversion procedures, seizure occurrence, intensive care unit admission, requirement for mechanical ventilation, and external ventricular drain placement. Functional neurological outcome measures, including modified Rankin Scale and Barthel Index scores, were not available within the database and therefore were not evaluated.

Statistical analysis

Risk differences, risk ratios, and odds ratios were calculated for all outcomes. Kaplan-Meier survival analysis was performed for mortality, and comparisons between groups were made using the log-rank test. A p-value of less than 0.05 was considered statistically significant.

Ethical approval

The TriNetX Global Collaborative Network provides access to de-identified patient data; therefore, this study was exempt from institutional review board approval.