Risk of Dementia With Renin-Angiotensin System Inhibitors Versus Calcium Channel Blockers in Hypertensive Adults: A Nationwide Multicenter Study

OBJECTIVE: The aim of this study was to evaluate whether renin-angiotensin system inhibitors (RASIs) reduce dementia risk independently of blood pressure control compared with calcium channel blockers (CCBs) in antihypertensive-naïve adults with hypertension. METHODS: This multicenter, new-user active comparator study included antihypertensive-naïve adults initiating RASIs or CCBs across 28 hospitals. Participants were matched 1:1 on baseline characteristics using propensity score matching (PSM). The primary outcome was incident all-cause dementia; secondary outcomes were Alzheimer's disease and vascular dementia. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: Of 164,918 eligible patients (median age 65 years [interquartile range 55-74]; 51.2% male), 54,042 PSM pairs initiating RASIs versus CCBs were included. During a median follow-up of 516 days, 344 incident dementia cases occurred. The incidence rate of all-cause dementia was lower among RASI initiators than CCB initiators (1.26 vs 1.89 per 1000 person-years). Initiation of RASIs was associated with a significantly lower risk of all-cause dementia (HR 0.68, 95% CI 0.55-0.84) and Alzheimer's disease (HR 0.59, 95% CI 0.43-0.81), but not vascular dementia (HR 0.74, 95% CI 0.50-1.11), compared with CCBs. There was no significant difference in dementia risk between initiators of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs). CONCLUSIONS: In adults with hypertension, initiation of RASIs was associated with a significantly lower risk of dementia compared with CCBs. No significant difference was observed between ACEIs and ARBs. Further validation is warranted.