Key result
The use of Angiotensin II stimulating antihypertensive medications reduced the risk of all-cause dementia by 13% (HR 0.87) compared to Angiotensin II inhibiting medications in observational studies.
Why the study?
Studies comparing the effects of angiotensin II stimulating versus inhibiting antihypertensive medications on dementia risk have reported inconsistent findings.
Does the use of Ang-II stimulating antihypertensive medications reduce the risk of dementia compared to Ang-II inhibiting antihypertensive medications?
Meta-Analysis (n=1,883,283)
Does the use of Ang-II stimulating antihypertensive medications reduce the risk of dementia compared to Ang-II inhibiting antihypertensive medications?
Observational evidence suggests that Ang-II stimulating antihypertensive medications may offer neuroprotective benefits and reduce the risk of dementia relative to Ang-II inhibiting medications.
May favor angiotensin II stimulating antihypertensives to lower dementia risk; extends inconsistent evidence but RCT data remain inconclusive.
Studies comparing the effects of Angiotensin II (Ang-II) stimulating and inhibiting antihypertensive medications (AHMs) on dementia risk have reported inconsistent findings. Based on the PRISMA guidelines, this study was performed to pool these findings. We searched PubMed, Scopus, Embase Ovid, PsycINFO, and CINAHL from inception to 22 May 2024 for randomised controlled trials (RCTs) and observational studies that compared the use of Ang-II stimulating (thiazides, Ang-II receptor blockers, and dihydropyridine calcium channel blockers) and inhibiting AHMs (β-blockers, angiotensin-converting enzyme inhibitors, and non-dihydropyridine calcium channel blockers) and the subsequent risk of developing dementia. Two reviewers independently performed study selection, data extraction, and quality assessment. Random effects meta-analysis models were used to calculate hazard ratios (HRs) or risk ratios (RRs) with their confidence intervals (CIs). All-cause dementia was the primary outcome. Alzheimer's disease (AD), vascular dementia (VD), and mild cognitive impairment (MCI) were secondary outcomes. We included 18 studies with 1,883,283 participants. Observational studies showed that the use of Ang-II stimulating AHMs reduced the risk of all-cause dementia by 13% (HR = 0.87; 95% CI = 0.82-0.93) compared with Ang-II inhibiting AHMs. The risk of AD was reduced by 12% (HR = 0.88; 95% CI = 0.86-0.90), VD by 19% (HR = 0.81; 95% CI = 0.72-0.91), and MCI by 24% (HR = 0.76; 95% CI = 0.68-0.85) in these studies. A meta-analysis of four RCTs revealed a non-significant 8% reduction in dementia risk with Ang-II stimulating AHMs versus control (RR = 0.92; 95% CI = 0.79-1.08). Observational evidence suggests that Ang-II stimulating AHMs may offer neuroprotective benefits relative to Ang-II inhibiting AHMs.
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Belachew et al. (2025) conducted a meta-analysis in Hypertension (n=1,883,283). Angiotensin II stimulating antihypertensive medications vs. Angiotensin II inhibiting antihypertensive medications was evaluated on All-cause dementia (HR 0.87, 95% CI 0.82-0.93, p=<0.01). The use of Angiotensin II stimulating antihypertensive medications reduced the risk of all-cause dementia by 13% (HR 0.87) compared to Angiotensin II inhibiting medications in observational studies.
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