Association between sacubitril/valsartan and risk of dementia in patients with heart failure: a nationwide cohort study

Aims To evaluate the risk of incident dementia associated with sacubitril/valsartan in patients with heart failure (HF) in South Korea. Methods and results We conducted a retrospective cohort study using the National Health Insurance Database in South Korea. Patients diagnosed with HF and prescribed either sacubitril/valsartan or angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) within 90 days of their first HF diagnosis between October 2017 and December 2020 were included. The primary outcome was incident dementia, categorized into Alzheimer's dementia and vascular dementia. Follow-up began after 1 year from the prescription date, to accommodate dementia onset latency, until the earliest occurrence of dementia, death, or end of study period (March 2023). After 1:4 propensity score matching, the hazard ratio (HR) with 95% confidence interval (CI) for dementia was estimated using a Cox proportional hazards model. Among 7085 sacubitril/valsartan users and 359 153 ACEI/ARB users, 6930 sacubitril/valsartan users [mean (SD) age, 61.7 (14.6) years; 70.9% male] were matched on propensity score to 27 720 ACEI/ARB users [mean (SD) age, 61.7 (15.8) years; 71.1% male]. During a mean follow-up of 2.2 and 2.3 years, dementia occurred in 200 (2.9%) sacubitril/valsartan users and 980 (3.5%) ACEI/ARB users, respectively. Sacubitril/valsartan showed a 16% lower risk of dementia compared with ACEI/ARB (HR 0.84; 95% CI 0.72–0.98). However, of 1180 cases of incident dementia, 1079 (91.4%) were categorized as Alzheimer's dementia and statistical significance was not reached in this main group. Conclusion Despite plausible biological mechanisms, no association between sacubitril/valsartan and an increased risk of dementia was observed in patients with HF.