Overall safety evaluation of the risk signals of sacubitril/valsartan: A postmarketing pharmacoepidemiology study from 2015 to 2024.

Abstract

Background: Sacubitril/valsartan is a widely used cardiovascular agent characterized by its dual inhibition of the renin-angiotensin-aldosterone system and neprilysin. However, existing evidence on the safety of sacubitril/valsartan is primarily limited to clinical studies; this results in an inability to provide a timely update on associated adverse events.

Aim: To mine and systematically describe adverse events related to sacubitril/valsartan from September 2015 to June 2024 using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: The reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network and multi-item gamma poisson shrinker methods were combined to detect risk signals in the FAERS database to identify potential associations between sacubitril/valsartan and adverse events.

Results: A total of 95,132 adverse event reports with sacubitril/valsartan as the "primary suspect" were collected. A total of 588 preferred terms and 27 system organ categories were obtained. The proportion of serious adverse events was 49.11%. Notably, hypotension (n=10,338, reporting odds ratio 13.71, proportional reporting ratio 13.23, information component 3.60, empirical Bayes geometric mean 12.08) and throat clearing (n=1495, reporting odds ratio 132.46, proportional reporting ratio 131.75, information component 6.03, empirical Bayes geometric mean 65.44) exhibited the highest incidence and signal intensity, respectively. In addition, uncommon, but apparently strong adverse event signals were observed, such as dyspnoea paroxysmal nocturnal and brain natriuretic peptide decreased. Cardiac dysfunction (n=444, reporting odds ratio 26.55, proportional reporting ratio 26.50, information component 4.47, empirical Bayes geometric mean 22.13) and memory impairment (n=2134, reporting odds ratio 3.35, proportional reporting ratio 3.33, information component 1.71, empirical Bayes geometric mean 3.27) also showed strong adverse event signals, which were not included in the instructions.

Conclusions: Psychiatric and neurological disorders, especially cardiac dysfunction and memory impairment, should be closely monitored in the clinical application of sacubitril/valsartan. At the same time, clinical professionals should be alert to the occurrence of adverse event signals not mentioned in the instructions, and take preventive measures to ensure the safety of clinical use.