Sacubitril/valsartan and the risk of incident dementia in heart failure: a nationwide propensity-matched cohort study

Hyun Jung Lee, Hyung Kwan Kim, Bong Seong Kim, Kyung Do Han, Soongu Kwak, Chan Soon Park, Tae Min Rhee, Jun Bean Park, Heesun Lee, Yong Jin Kim

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Background: Sacubitril acts to inhibit neprilysin and as neprilysin is involved in amyloid-beta degradation in the central nervous system, and there is concern that sacubitril/valsartan may increase the risk of dementia. We aimed to compare the risk of incident dementia associated with sacubitril/valsartan and angiotensin II receptor blockers (ARBs). Methods: Patients with heart failure with reduced ejection fraction treated with either sacubitril/valsartan or ARB, identified from the Korean National Health Insurance Service database, were matched in a 1:2 ratio using propensity scores (6789 on sacubitril/valsartan and 13,578 on ARBs) and followed up for incident dementia. Results: During a mean follow-up of 2.5 years, 526 (2.6%) patients were newly diagnosed with dementia: Alzheimer dementia in 282, vascular dementia in 8, and other dementia in 236. There was no significant difference in the risk of overall dementia (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.70–1.01), Alzheimer dementia (HR 0.85, 95% CI 0.67–1.10), vascular dementia (HR 0.98, 95% CI 0.23–4.11), and all other dementias (HR 0.81, 95% CI 0.62–1.07) between sacubitril/valsartan users and ARB users. These results were consistent regardless of initial sacubitril/valsartan dose and subgroups including old age, previous mild cognitive impairment, previous stroke, and concomitant antiplatelet or anticoagulation. Sensitivity analysis with a 1-year lag period for dementia assessment confirmed the main analysis. Meanwhile, risk of incident stroke was lower in sacubitril/valsartan users compared to ARBs users. Conclusions: In a nationwide propensity-matched cohort of patients with heart failure, sacubitril/valsartan was not associated with an increased risk of incident dementia compared to ARBs. Graphic abstract: Sacubitril/valsartan and the risk of incident dementia in heart failure. ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor. (Figure presented.)

Original languageEnglish
Pages (from-to)875-883
Number of pages9
JournalClinical Research in Cardiology
Volume113
Issue number6
DOIs
StatePublished - Jun 2024

Bibliographical note

Publisher Copyright:
© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2023.

Keywords

  • Adverse drug event
  • Dementia
  • Heart failure
  • Neprilysin

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