Endothelial and Vascular Toxicity Signals Associated With Doxorubicin: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System ( FAERS ) Database

PURPOSE: 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). METHODS: 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). RESULTS: 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. CONCLUSION: 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. This study investigated the latest cardiac‐related adverse events (AEs) linked with doxorubicin (DOX) using the patient case reports submitted to the Food and Drug Administration Adverse Event Reporting System (FAERS) database. To determine the significant AEs associated with DOX, we collected case reports submitted to FAERS from 2004 to 2025 using OpenVigil software and then analyzed them using algorithms that can detect the likelihood of an AE to be associated with the drug of interest. A positive signal detected indicates a potential safety concern that may require further investigation to assess potential causation. A total of 2421 reports on cardiac‐related AEs were collected from FAERS throughout the study period. Most reports involved females between 18 and 65 years diagnosed with breast cancer or lymphoma. Based on the detection algorithms, the majority of the signals were of moderate to strong signal intensity, with cardiac‐related signals like heart failure being the topmost reported AEs strongly linked to DOX, followed by novel vascular‐related AEs such as endothelial dysfunction. Death and hospitalization were the two most commonly reported serious outcomes linked with DOX‐induced AEs.