Lee_2025_Am.J.Cardiovasc.Drugs__

BACKGROUND: Cholinesterase inhibitors (ChEIs) are widely prescribed for dementia, but their effects on cardiovascular outcomes in high-risk populations remain unclear. OBJECTIVES: Our objective was to evaluate the association between ChEI use and the risk of major adverse cardiovascular events (MACE) and all-cause mortality among individuals with high cardiovascular risk. METHODS: We conducted a retrospective cohort study using data from the Chang Gung Research Database in Taiwan from 2001 to 2022. Individuals aged <= 50 years with cardiovascular risk factors who received ChEIs were matched 1:1 with non-users based on birth year, sex, history of dementia, and cardiovascular comorbidities. The primary outcome was time to first MACE, defined as hospitalization for acute ischemic stroke, acute myocardial infarction, or cardiovascular death. Secondary outcomes included individual cardiovascular events, heart failure, and all-cause mortality. Competing risk and survival analyses were performed using Fine and Gray subdistribution hazard models and Cox proportional hazards models, respectively. RESULTS: Among 21,598 matched patients (mean age 77.7 years; 61.1% female), ChEI use was associated with a significantly reduced risk of MACE (adjusted subdistribution hazard ratio 0.79; 95% confidence interval 0.74-0.84; P < 0.001) and acute myocardial infarction (adjusted subdistribution hazard ratio 0.70; 95% confidence interval 0.55-0.90; P = 0.006). ChEI users also had significantly improved overall survival (log-rank P < 0.001). CONCLUSIONS: ChEI use is associated with a lower risk of major cardiovascular events and improved survival in patients at high cardiovascular risk. These findings suggest potential cardiovascular benefits of ChEIs beyond cognitive symptom management.