Comparative analysis of adverse events between sacubitril/valsartan and valsartan using the FAERS database: a disproportionality analysis

Expert Opin Drug Saf. 2025 Nov 22:1-11. doi: 10.1080/14740338.2025.2591388. Online ahead of print.

ABSTRACT

BACKGROUND: This study conducts a comprehensive comparative analysis of adverse event (AE) signals between sacubitril/valsartan and valsartan, two pivotal cardiovascular drugs for heart failure and hypertension, utilizing the FAERS database to identify differential safety risks and optimize clinical monitoring.

RESEARCH DESIGN AND METHODS: Data from the FAERS database (2004Q1-2024Q2) were analyzed using disproportionality analysis and Bayesian methods to detect and evaluate AE signals associated with sacubitril/valsartan and valsartan, enabling a comparative assessment.

RESULTS: A total of 102,678 adverse event reports (AERs) were linked to sacubitril/valsartan, compared to 24,318 AERs for valsartan. Sacubitril/valsartan demonstrated the strongest association with cardiac disorders (ROR 4.13), while valsartan exhibited the highest association with vascular disorders (ROR 2.67). Common AE signals aligned with the respective drug labels. Unexpected AEs for sacubitril/valsartan included myocardial infarction (n = 2,909, ROR 6.45), arrhythmia (n = 1,691, ROR 4.07), decreased activity (n = 544, ROR 11.13), and fluid imbalance (n = 44, ROR 11.98). Unique AEs for valsartan included fear of disease (n = 137, ROR 47.57), thrombotic stroke (n = 31, ROR 25.60), merycism (n = 30, ROR 79.41), and eosinophilic colitis (n = 11, ROR 20.62).

CONCLUSIONS: Sacubitril/valsartan and valsartan exhibit distinct AE risk profiles in cardiovascular disease treatment, underscoring the need for large-scale clinical trials and mechanistic studies on sacubitril to validate these findings.

PMID:41248909 | DOI:10.1080/14740338.2025.2591388