Endothelial and Vascular Toxicity Signals Associated With Doxorubicin: A Pharmacovigilance Analysis of the FDA...

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. Thus, this study performed data mining of the FDA Adverse Event Reporting System (FAERS) to detect and analyze DOX-induced cardiac-related adverse events (AEs).

Data from 2004 to 2025, where DOX was the primary suspect, were extracted from FAERS via OpenVigil. Using the Medical Dictionary for Regulatory Activities, AEs were categorized into preferred terms (PTs) and system organ classes (SOCs). This study used descriptive analysis and signal detection algorithms including Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN).

A total of 2421 reports of DOX-associated AEs were extracted in FAERS. Reports primarily involved female cancer patients (55.02%) between 18and 65 years (48.12%) from the United States. Most signals were of moderate to strong signal intensity, with cardiotoxicity, cardiac failure, and cardiomyopathy being the most reported. Interestingly, while cardiac disorders were mainly found to be strongly linked to DOX, novel vascular AEs like endothelial dysfunction were also among the top signals strongly associated with DOX. Out of the six serious AEs associated with DOX-induced cardiotoxicities, "Death" and "Initial/prolonged hospitalization" were the most commonly reported.

This study provides valuable insights into DOX-induced cardiovascular toxicity using real-world data from FAERS. Vascular events like endothelial dysfunction were shown to be significant novel AEs experienced by cancer patients undergoing treatment with DOX. Thus, careful monitoring of potential DOX-AEs associations will help improve the risk-benefit ratio of DOX-treated patients.