OBJECTIVES: Treatment with ototoxic drugs can lead to hypoacusis or hearing loss. Hypoacusis can arise at any time during or after the treatment with ototoxic drugs which is either gradual or sudden in onset. Sacubitril/Valsartan is an angiotensin receptor neprilysin inhibitor (ARNi) used in the treatment of heart failure. This study aimed to find the association of Sacubitril/Valsartan with Hypoacusis by disproportionality analysis of US FDA Adverse Event Reporting System (FAERS).

METHODS: The FAERS data which has been used in this study is publicly available from July 2015 to September 2020. Disproportionality analysis was performed using Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) with 95% confidence intervals (CI). A value of PRR ≥2.0 with a Chi-squared test statistic of ≥4.0, at least three reports (n ≥3) of that preferred term (PT) and ROR-1.96SE>1 is considered statistically significant.

RESULTS: A total of 20,760 reports have been reported in the FDA database for hypoacusis. Amongst which 841 (4.05%) reports were associated with Sacubitril/Valsartan. The estimated ROR and PRR for Sacubitril/Valsartan were 8.415 (95% CI 7.849-9.022) and 8.284 (95% CI 7.736-8.87) respectively. The ROR and PRR (ROR 9.252, 95% CI 8.62-9.93; PRR 9.091, 95% CI 8.481-9.745) were recalculated after removing the reports where Sacubitril/Valsartan is co-administered with drugs that are known to cause hypoacusis. The signal strength was well above the threshold which indicates a possible association.

CONCLUSIONS: The study suggested that there is an association between Sacubitril/Valsartan and hypoacusis which was not listed during pre-clinical and clinical studies. Even though the causal relationship cannot be proved definitely, the increase in number of cases reported over the course of period could articulate an association. Also, further larger studies needed to be carried out to to confirm this hypothesis.