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

• Published in: Clinical research in cardiology 2024-06, Vol.113 (6), p.875-883
• Main Authors: Lee, Hyun-Jung, Kim, Hyung-Kwan, Kim, Bong-Seong, Han, Kyung-Do, Kwak, Soongu, Park, Chan Soon, Rhee, Tae-Min, Park, Jun-Bean, Lee, Heesun, Kim, Yong-Jin
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Aminobutyrates - adverse effects; Aminobutyrates - therapeutic use; Angiotensin; Angiotensin II; Angiotensin Receptor Antagonists - adverse effects; Angiotensin Receptor Antagonists - therapeutic use; Anticoagulants; Biphenyl Compounds; Cardiology; Central nervous system; Cognitive ability; Congestive heart failure; Dementia; Dementia - epidemiology; Dementia disorders; Drug Combinations; Female; Follow-Up Studies; Heart failure; Heart Failure - epidemiology; Humans; Incidence; Male; Medicine; Medicine & Public Health; Middle Aged; Neprilysin; Original Paper; Propensity Score; Receptors; Republic of Korea - epidemiology; Retrospective Studies; Risk analysis; Risk Assessment - methods; Risk Factors; Sensitivity analysis; Stroke Volume; Subgroups; Tetrazoles - adverse effects; Valsartan; Vascular dementia
• ISSN: 1861-0684; 1861-0692
• DOI: 10.1007/s00392-023-02322-0

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.