Angiotensin receptor blockers and dementia risk in older adults: A target trial emulation

INTRODUCTION: Whether antihypertensive drug class influences dementia risk beyond blood pressure lowering remains uncertain. METHODS: We emulated a target trial comparing new initiation of angiotensin receptor blockers (ARBs) versus calcium channel blockers (CCBs) among dementia-free adults aged ≥65 years in a nationwide Japanese database. Weighted discrete-time hazards models estimated intention-to-treat and per-protocol effects, accounting for censoring and death. RESULTS: Among 52,019 eligible new users followed for a median of 3.6 years, 3524 incident dementia events occurred. ARB initiation was associated with lower all-cause dementia risk than CCB initiation (hazard ratio [HR], 0.916; 95% confidence interval [CI], 0.852-0.985), with similar achieved blood pressure. For Alzheimer's disease (2231 events), the association was not statistically significant (HR, 0.930; 95% CI, 0.849-1.018). The association was stronger for vascular dementia (129 events; HR, 0.617; 95% CI, 0.409-0.930). DISCUSSION: ARB initiation was associated with modestly lower dementia risk, particularly vascular dementia, versus CCB initiation.