The real-world safety of sacubitril / valsartan among older adults (≥75): A pharmacovigilance study from the FDA data

• Published in: International journal of cardiology Vol. 397; p. 131613
• Main Authors: Lerman, Tsahi T., Greenberg, Noam, Fishman, Boris, Goldman, Adam, Talmor-Barkan, Yeela, Bauer, Menachem, Goldberg, Idan, Goldberg, Elad, Kornowski, Ran, Krause, Ilan, Levi, Amos, Cohen, Eytan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.02.2024
• Subjects: Acute Kidney Injury - chemically induced; Acute Kidney Injury - diagnosis; Acute Kidney Injury - epidemiology; Aged; Aminobutyrates - adverse effects; Angioedema - chemically induced; Angioedema - diagnosis; Angioedema - epidemiology; Angiotensin Receptor Antagonists - adverse effects; Angiotensin-Converting Enzyme Inhibitors; ARNI; Biphenyl Compounds - adverse effects; Drug Combinations; Elderly; Heart failure; Heart Failure - chemically induced; Heart Failure - epidemiology; Humans; Hyperkalemia - chemically induced; Hyperkalemia - diagnosis; Hyperkalemia - epidemiology; Hypotension - chemically induced; Hypotension - diagnosis; Hypotension - epidemiology; Older adults; Pharmacovigilance; Retrospective Studies; Sacubitril/valsartan; Stroke Volume; Tetrazoles - adverse effects; Valsartan - adverse effects; Heart failure; Sacubitril/valsartan; ARNI; Elderly; Older adults
• ISSN: 0167-5273; 1874-1754; 1874-1754
• DOI: 10.1016/j.ijcard.2023.131613

Heart failure is a major cause of morbidity and mortality among older adults. Sacubitril-Valsartan (Sac/Val) has been shown to improve patients' outcomes; however, its safety profile among older adults has not been adequately examined. We therefore aimed to examine its safety profile among this population. We conducted a retrospective pharmacovigilance study utilizing the FDA's database of safety reports (FAERS). We employed disproportionality analysis comparing Sac/Val to angiotensin receptor blockers (ARBs). We aim to evaluate the reporting of pre-defined adverse events associated with Sac/Val (hypotension, acute kidney injury (AKI), hyperkalemia and angioedema) in two age groups: adults (< 75 years) and older adults (≥ 75). For each subgroup, we calculated reporting odds ratio (ROR) and compared them by calculating P for interaction. The FAERS database encompassed 18,432 unique reports of Sac/Val. Of them, 12,630 (68.5%) subjects were adults (< 75 years), and 5802 (31.5%) were older adults (≥ 75 years), with a median age (IQR) of 68 (59–77). When compared to ARBs, Sac/Val was associated with higher reporting of hypotension, lower reporting of acute kidney injury (AKI) and hyperkalemia, and similar reporting of angioedema. Notably, we did not observe a significant interaction between the age subgroups and the risk estimates (AKI: Pinteraction = 0.72, hyperkalemia: Pinteraction = 0.94, hypotension: Pinteraction = 0.31, and angioedema: Pinteraction = 0.61). In this postmarking study, none of the prespecified adverse events was reported more frequently in older adults. These findings provide reassurance for safety use of Sac/Val in older adults. •Sacubitril/Valsartan vs. ARB: Higher reporting of hypotension, lower AKI & hyperkalemia, similar angioedema reporting.•No significant interaction between the patients age subgroups (≥75 vs. <75) and the estimated risk of reporting.•These findings provide reassurance for safety use of Sacubitril/Valsartan in older-adults patients.