Cardiovascular toxicity profile of doxorubicin: data mining of the FDA adverse event reporting system (FAERS)

Abstract Funding Acknowledgements None. Background Doxorubicin (DOX), an effective anticancer agent, is associated with dose-dependent cardiovascular toxicity. Understanding its mechanisms and risk factors will facilitate novel interventions to minimize DOX-induced cardiovascular toxicity. Purpose We aimed to perform a comprehensive analysis of the Food and Drug Administration Adverse Event Reporting System (FAERS) database to identify, describe, and quantify the latest cardiovascular DOX-associated adverse-events (AEs). Methods Data from 2004 Q1 – 2022 Q3, where DOX was the primary-suspect, were extracted from FAERS via OpenVigil 2.1. For data collection, preferred-terms (PTs) from Medical Dictionary for Regulatory Activities (MedDRA) were used, while ROR with 95% CIs for disproportionality analysis was performed. Results 1987 reports were collected for significant PTs. The most prevalent DOX-associated AE was heart failure (77.6%, n=1542), followed by cardiac fibrosis and inflammation (7.75%, n=154) and vascular disorders (7.45%, n=148). Others include arrhythmias, systemic inflammation, and endothelial dysfunction. Most patients were females (51.1%, n=1016), 18-64 years-old (41%, n = 815), primarily from Europe (41.87%, n=832) and the United States (34.12%, n = 678). Six outcomes were associated with DOX-induced cardiotoxicities, mainly "Death", "Initial/prolonged hospitalization", and "Others". Conclusion This study provides valuable insights on DOX-induced cardiovascular toxicity using real-world data from FAERS.Total Case Count of all Adverse EventPatients' Demographics and outcomes