Endothelial and Vascular Toxicity Signals Associated With Doxorubicin: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS) Database.
Cerbito E, Kattan L, et al. • Pharmacoepidemiology and drug safety • 2026
Pharmacovigilance analysis of FAERS data from 2004–2025 found that doxorubicin is strongly associated with cardiac adverse events including cardiomyopathy and cardiac failure, and also identified novel vascular adverse events such as endothelial dysfunction as significant signals, with death and hospitalization being the most commonly reported serious outcomes.
Key Findings
Results
A total of 2421 reports of doxorubicin-associated adverse events were extracted from the FAERS database over the study period.
Data spanned from 2004 to 2025, extracted via OpenVigil software.
Doxorubicin was designated as the primary suspect drug in all extracted reports.
Reports were categorized using the Medical Dictionary for Regulatory Activities (MedDRA) into preferred terms (PTs) and system organ classes (SOCs).
Signal detection used four algorithms: PRR, ROR, MGPS, and BCPNN.
Results
Reports of doxorubicin-associated adverse events primarily involved female cancer patients between 18 and 65 years of age from the United States.
Female patients accounted for 55.02% of reports.
Patients aged 18–65 years represented 48.12% of reports.
Most reports originated from the United States.
The most common cancer diagnoses among reporters were breast cancer and lymphoma.
Results
Cardiotoxicity, cardiac failure, and cardiomyopathy were the most commonly reported adverse events and were strongly linked to doxorubicin by signal detection algorithms.
Most signals were characterized as moderate to strong signal intensity.
Cardiac disorders were 'mainly found to be strongly linked to DOX' across all four signal detection algorithms (PRR, ROR, MGPS, BCPNN).
A positive signal detected indicates a potential safety concern that may require further investigation to assess potential causation.
Cardiac failure and cardiomyopathy were among the top preferred terms identified.
Results
Endothelial dysfunction was identified as a novel vascular adverse event strongly associated with doxorubicin.
Vascular adverse events such as endothelial dysfunction were described as 'novel' findings in this pharmacovigilance analysis.
Endothelial dysfunction was among the 'top signals strongly associated with DOX.'
This vascular signal appeared alongside established cardiac disorder signals.
The authors described this as a 'significant novel AE experienced by cancer patients undergoing treatment with DOX.'
Results
Death and initial/prolonged hospitalization were the most commonly reported serious outcomes among the six serious adverse events associated with doxorubicin-induced cardiotoxicities.
Six serious adverse event categories were identified in association with DOX-induced cardiotoxicities.
'Death' and 'Initial/prolonged hospitalization' were ranked as the two most frequently reported serious outcomes.
These outcomes reflect real-world severity of doxorubicin-associated cardiovascular toxicity as captured in spontaneous reporting data.
Methods
The study used four complementary pharmacovigilance signal detection algorithms to assess the strength of association between doxorubicin and cardiac adverse events.
Algorithms used were: Proportional Reporting Ratio (PRR), Reporting Odds Ratio (ROR), Multi-item Gamma Poisson Shrinker (MGPS), and Bayesian Confidence Propagation Neural Network (BCPNN).
These algorithms detect disproportionate reporting of adverse events relative to all drugs in the database.
The study used descriptive analysis alongside the signal detection algorithms.
A positive signal from these algorithms indicates a potential safety concern requiring further investigation, not confirmed causation.
What This Means
This research analyzed reports submitted to the FDA's Adverse Event Reporting System (FAERS) between 2004 and 2025 to better understand the types of heart and blood vessel problems reported in patients treated with doxorubicin, a widely used chemotherapy drug. Using computerized detection methods, the researchers examined 2,421 case reports where doxorubicin was identified as the primary drug of concern. Most of these reports came from women between 18 and 65 years old, primarily diagnosed with breast cancer or lymphoma, and most were from the United States.
The analysis confirmed well-known concerns about doxorubicin's effects on the heart, including heart failure and cardiomyopathy (weakening of the heart muscle), which showed strong statistical signals across all detection methods. Importantly, the study also identified damage to the inner lining of blood vessels — called endothelial dysfunction — as a significant and previously underappreciated adverse event linked to doxorubicin. Among serious outcomes, death and hospitalization were the most frequently reported consequences of these cardiovascular side effects.
This research suggests that the cardiovascular risks of doxorubicin extend beyond the heart itself to include the blood vessels, and that endothelial dysfunction may be an important but underrecognized side effect in cancer patients receiving this treatment. The findings highlight the potential value of monitoring both heart function and vascular health during doxorubicin therapy, and may help guide future research into ways to reduce cardiovascular harm while preserving the drug's effectiveness against cancer.
Cerbito E, Kattan L, Dhulkifle H, Korashy H, Maayah Z. (2026). Endothelial and Vascular Toxicity Signals Associated With Doxorubicin: A Pharmacovigilance Analysis of the FDA Adverse Event Reporting System (FAERS) Database.. Pharmacoepidemiology and drug safety. https://doi.org/10.1002/pds.70474