Moderate to high telmisartan exposure was associated with a reduced incidence of Alzheimer's disease in African Americans compared to low or no exposure (HR 0.77; 95% CI 0.65-0.91; P=0.0022).
Observational (n=5,620,000)
Does moderate/high telmisartan exposure reduce the incidence of Alzheimer's disease in older African Americans?
Telmisartan exposure is associated with a significantly reduced risk of Alzheimer's disease specifically in African Americans, suggesting a potential race-specific neuroprotective benefit.
Estimación del efecto: HR 0.77 (95% CI 0.65-0.91)
valor p: p=0.0022
INTRODUCTION: African Americans (AAs) and European Americans (EAs) differ in Alzheimer's disease (AD) prevalence, risk factors, and symptomatic presentation and AAs are less likely to enroll in AD clinical trials. METHODS: We conducted race-conscious pharmacoepidemiologic studies of 5.62 million older individuals (age ≥60) to investigate the association of telmisartan exposure and AD outcome using Cox analysis, Kaplan-Meier analysis, and log-rank test. We performed Mendelian randomization (MR) analysis of large ethnically diverse genetic data to test likely causal relationships between telmisartan's target and AD. RESULTS: We identified that moderate/high telmisartan exposure was significantly associated with a reduced incidence of AD in the AAs compared to low/no telmisartan exposure (hazard ratio HR = 0.77, 95% CI: 0.65-0.91, p-value = 0.0022), but not in the non-Hispanic EAs (HR = 0.97, 95% CI: 0.89-1.05, p-value = 0.4110). Sensitivity and sex-/age-stratified patient subgroup analyses identified that telmisartan's medication possession ratio (MPR) and average hypertension daily dosage were significantly associated with a stronger reduction in the incidence of both AD and dementia in AAs. Using MR analysis from large genome-wide association studies (GWAS) (over 2 million individuals) across AD, hypertension, and diabetes, we further identified AA-specific beneficial effects of telmisartan for AD. DISCUSSION: Randomized controlled trials with ethnically diverse patient cohorts are warranted to establish causality and therapeutic outcomes of telmisartan and AD. HIGHLIGHTS: Telmisartan is associated with lower risk of Alzheimer's disease (AD) in African Americans (AAs). Telmisartan is the only angiotensin II receptor blockers having PPAR-γ agonistic properties with beneficial anti-diabetic and renal function effects, which mitigate AD risk in AAs. Mendelian randomization (MR) analysis demonstrates the specificity of telmisartan's protective mechanism to AAs.
Zhang et al. (Fri,) conducted a observational in Alzheimer's disease (n=5,620,000). Telmisartan vs. Low/no telmisartan exposure was evaluated on Incidence of Alzheimer's disease (HR 0.77, 95% CI 0.65-0.91, p=0.0022). Moderate to high telmisartan exposure was associated with a reduced incidence of Alzheimer's disease in African Americans compared to low or no exposure (HR 0.77; 95% CI 0.65-0.91; P=0.0022).