Global Pharmacovigilance Analysis of Epirubicin-Associated Cardiotoxicity: Real-World Insights from FAERS and EudraVigilance Databases (2004–2025)

Abstract

Background: Epirubicin is a cornerstone of chemotherapy, yet its dose-limiting cardiotoxicity remains a significant clinical challenge. This study aimed to characterize the real-world cardiac safety profile of epirubicin using global pharmacovigilance databases.

Methods: We performed a retrospective analysis of the FDA Adverse Event Reporting System (FAERS) (2004–2025) and validated findings using the EudraVigilance (EV) database (2003–2025). Disproportionality was assessed using ROR, PRR, IC, and EBGM algorithms. Time-to-onset (TTO) and clinical outcomes were systematically evaluated.

Results:Analysis of the FAERS and EudraVigilance databases (2004–2025) revealed a rising trend in epirubicin-associated cardiotoxicity, peaking in recent years with a marked female predominance (up to 87.56%) and high clinical severity (99.22% serious). Signal mining confirmed robust associations with heart failure (ROR=6.60) and dilated cardiomyopathy (ROR=34.97), with the highest intensities observed for heart failure with mid-range ejection fraction (ROR=406.37). Median time-to-onset was 36 days, though males experienced significantly faster onset than females (22 vs. 49 days). Age-stratified analysis identified specific vulnerabilities, notably dilated cardiomyopathy in pediatric patients and left ventricular dilatation in the elderly. External validation across both databases identifies epirubicin as a sustained, independent risk factor for diverse and severe cardiac adverse events.

Conclusion: Epirubicin-associated cardiotoxicity is characterized by early-onset, high-severity events with distinct sex and age-specific risk profiles. Intensive cardiac monitoring, particularly within the first 40 days of treatment, is critical for high-risk cohorts.