Cardiovascular

Renin-Angiotensin System Inhibitor Use and Mortality in Older Hypertensive Patients With and Without Dementia: A Nationwide Registry-Based Cohort Study.

TL;DR

RASI use was associated with lower all-cause mortality among older hypertensive patients, including those with dementia, with ARB associated with lower mortality than ACEI in the full cohort.

Key Findings

RASI use was associated with lower all-cause mortality in the full cohort of older hypertensive patients.

  • Hazard ratio 0.93 (95% CI 0.91–0.95, p < 0.001) for RASI users versus non-users in the full cohort
  • Study included 158,176 hypertensive patients with exposure to RASI medications (21,152 RASI users and 137,024 non-users)
  • Prevalent users were excluded to reduce immortal time bias
  • Propensity score matching was used to balance measured confounders
  • Data were drawn from Swedish national registries covering 2007–2018

RASI use was associated with lower all-cause mortality specifically among patients with dementia.

  • Hazard ratio 0.88 (95% CI 0.85–0.92) for RASI users versus non-users among patients with dementia
  • The association was stronger in dementia patients (HR 0.88) than in the full cohort (HR 0.93)
  • This is a nationwide registry-based cohort study, so findings are observational
  • The study addresses the concern that cardiovascular risk factors are often undertreated in patients with dementia

Compared to ACEI, ARB use was associated with lower mortality in the full cohort.

  • Hazard ratio 0.90 (95% CI 0.85–0.96) for ARB versus ACEI users in the full cohort
  • The difference between ARB and ACEI was not statistically significant in the dementia subgroup
  • Individual drug comparisons for enalapril, ramipril (ACEI) and losartan, candesartan (ARB) versus other RASI users were consistent with class-level findings

The study population consisted of older hypertensive patients from Swedish national registries spanning over a decade.

  • Data were collected from Swedish national registries between 2007 and 2018
  • Total cohort included 158,176 hypertensive patients with RASI medication exposure
  • RASI users numbered 21,152 and non-users numbered 137,024 after excluding prevalent users
  • Cox regression models were used to compare mortality risk across drug groups
  • Propensity score matching was applied to balance measured confounders between comparison groups

Individual RASI agents (enalapril, ramipril, losartan, candesartan) showed results consistent with their class-level findings when compared to other RASI users.

  • Four specific agents were examined: enalapril and ramipril (ACEI class) and losartan and candesartan (ARB class)
  • Each agent was compared to other RASI users rather than to non-users
  • Individual drug findings were described as 'consistent with class-level findings'
  • This analysis allowed assessment of whether class-level effects were driven by specific agents

The authors concluded that observational findings support continued attention to evidence-based hypertension treatment in patients with dementia.

  • The paper frames its findings in the context of known undertreatment of cardiovascular risk factors in dementia patients
  • The authors explicitly note these are observational findings
  • RASI are described as first-line treatments for hypertension
  • The study design used nationwide registry data to maximize generalizability within the Swedish population

What This Means

This research suggests that older patients with high blood pressure who take renin-angiotensin system inhibitors (RASI) — a common class of blood pressure medications that includes ACE inhibitors and angiotensin receptor blockers (ARBs) — have a lower risk of dying from any cause compared to those who do not take these medications. The study analyzed data from over 158,000 patients in Swedish national health registries between 2007 and 2018. Importantly, this survival benefit was also seen among patients who had both high blood pressure and dementia, a group that is often undertreated for cardiovascular conditions. The research also found differences within the RASI drug class: ARBs were associated with slightly lower mortality than ACE inhibitors in the overall group, though this difference was not statistically significant among dementia patients specifically. When looking at individual drugs like enalapril, ramipril, losartan, and candesartan, the results were consistent with what was found at the class level. This research suggests that blood pressure treatment with RASI medications should not be neglected in people with dementia, as it appears to be associated with survival benefits similar to those seen in the broader hypertensive population. Because this is an observational study using registry data rather than a clinical trial, it cannot prove that the medications directly caused the lower mortality, but the findings reinforce the importance of evidence-based hypertension management even in older patients with dementia.

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Citation

Villa Lopez M, Hoang M, Xu H, Norgren J, Petek B, Secnik J, et al.. (2026). Renin-Angiotensin System Inhibitor Use and Mortality in Older Hypertensive Patients With and Without Dementia: A Nationwide Registry-Based Cohort Study.. Journal of clinical hypertension (Greenwich, Conn.). https://doi.org/10.1111/jch.70350