Abstract 264: Tachyarrhythmias Associated With Sacubitril-valsartan - A Pharmacovigilance Analysis:

Abstract

Background: Sacubitril-valsartan is a combination of a neprilysin inhibitor and an angiotensin II receptor blocker respectively. Sacubitril-valsartan has become a standard of care in the treatment of patients with Congestive Heart Failure (CHF) with reduced EF. During its clinical trials and upon review of U.S. Food and Drug Administration (FDA) approval, sacubitril-valsartan exhibited a side effect profile including hyperkalemia, hypotension, renal dysfunction, and angioedema. Recently, sacubitril-valsartan was also approved for the treatment of CHF patients with preserved EF. Objective: In view of new indications and increased usage, it is important to establish the updated safety profile of sacubitril-valsartan in the general population since the PARADIGM-HF trial. Methods: We explored reported Adverse Events (AEs) of sacubitril-valsartan using the FDA Adverse Event Reporting System. A total of 57,958 AEs were reported until August 2021. Total of 16,658 (28.7%) AEs were reported by HCPs, which were further analyzed. AEs were analyzed in men (56.7%) vs women (25.3%), and also in 3 age groups of 18-64, 65-85, >85. Results: Out of 16,658 AEs, the most frequently reported AE was hypotension (17.2%). Other commonly reported AEs were renal dysfunction (14.3%), allergic reactions including angioedema (10.8%), GI distress (8.8%), tachyarrhythmias (5.8%), hyperkalemia (4.5%), and cough (3.0%). Out of 16,658 AEs, 11,631 (69%) were deemed serious and 4,422 (26.5%) resulted in hospitalization. Deaths were attributed to 3,909 serious AEs (23.5%). In the age group of 18-64, events of atrial fibrillation were less among women compared to men (1% vs 3%), while total events of ventricular tachycardia were noted more among men compared to women (2% vs 0.5%). Conclusion: Most of the reported AEs were consistent with the observed AEs from PARADIGM-HF except for tachyarrhythmia. There are few reports documenting arrhythmias followed by the use of sacubitril-valsartan, however, the clear mechanism is unknown. Despite the wide use of sacubitril-valsartan, there is currently limited data on the safety profile. In future with the increasing use, further randomized controlled trials (RCTs) are needed to better understand the safety profile of the medication.