Comparative effects of angiotensin II stimulating and inhibiting antihypertensives on dementia risk: a systematic review and meta-analysis.

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.