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Cardiotoxicity associated with antineoplastic agents: a pharmacovigilance study based on FDA adverse event reporting
Xiaohan Qiu1, Qinxiao Li2, Yiyin Rong2
1Department of Cardiology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Background:
Cardiovascular adverse events represent critical complications of antineoplastic therapy with profound implications for cancer survivorship and treatment outcomes. Despite the clinical significance, comprehensive pharmacovigilance data characterizing distinctive cardiotoxicity profiles across modern cancer therapeutics remain limited.
Objectives:
This investigation systematically analyzes cardiotoxicity patterns associated with antineoplastic agents using the FDA Adverse Event Reporting System (FAERS) database to inform evidence-based cardiovascular monitoring strategies.
Design:
A retrospective pharmacovigilance study utilizing disproportionality analysis and time-to-onset evaluation.
Methods:
We conducted a comprehensive analysis of FAERS data spanning 2004-2024, employing validated disproportionality metrics including reporting odds ratio (ROR) and proportional reporting ratio (PRR) to detect significant drug-event associations. Advanced time-to-onset analysis revealed temporal patterns of cardiotoxicity development across therapeutic classes. Statistical significance was defined as ROR >1 with 95% confidence intervals excluding 1.0, and PRR >2 with chi-square >4.
Results:
Analysis of 18,289,374 reports identified 51,402 cases of antineoplastic-related cardiovascular toxicity, demonstrating distinct class-specific patterns. Anthracyclines exhibited profound associations with structural cardiac damage (doxorubicin-cardiomyopathy: ROR = 20.64, 95% CI: 19.87-21.45). Immune checkpoint inhibitors demonstrated unprecedented immune-mediated cardiac inflammation (pembrolizumab-myocarditis: ROR = 245.36, 95% CI: 218.42-275.88). Fluoropyrimidines showed distinctive vasospastic effects (5-fluorouracil-Prinzmetal angina: ROR = 18.27, 95% CI: 14.72-22.69). Critical temporal patterns emerged: fluoropyrimidines caused early-onset cardiotoxicity (median: 11 days, IQR: 4-28), anthracyclines showed intermediate onset (doxorubicin median: 64 days, IQR: 21-156; epirubicin median: 72 days, IQR: 28-168), while mitoxantrone demonstrated delayed effects (median: 457 days, IQR: 182-891). Cardiogenic shock emerged as the most lethal manifestation with a 43.08% mortality rate (95% CI: 40.12-46.14).
Conclusion:
This landmark pharmacovigilance study reveals previously uncharacterized temporal and mechanistic patterns of antineoplastic cardiotoxicity, providing an essential evidence-based framework for cardiovascular monitoring strategies. The findings highlight critical intervention windows: immediate monitoring for fluoropyrimidines, intermediate surveillance for anthracyclines (2-6 months), and extended follow-up for agents like mitoxantrone (>12 months). These insights support the development of risk-stratified cardio-oncology protocols tailored to specific therapeutic classes.
Insights
This study analyzed cancer drug side effects using FDA data, revealing distinct heart risks for different therapies. It highlights specific monitoring times for drugs like anthracyclines and immune checkpoint inhibitors to improve patient safety.
Area of Science:
- Cardio-oncology
- Pharmacovigilance
- Drug safety
Background:
- Cardiovascular adverse events are critical complications of antineoplastic therapy, impacting cancer survivorship.
- Limited pharmacovigilance data exists for cardiotoxicity profiles across modern cancer therapeutics.
Purpose of the Study:
- To systematically analyze cardiotoxicity patterns associated with antineoplastic agents.
- To inform evidence-based cardiovascular monitoring strategies using FDA Adverse Event Reporting System (FAERS) data.
Main Methods:
- Retrospective pharmacovigilance study using disproportionality analysis (ROR, PRR) and time-to-onset evaluation.
- Analysis of FAERS data from 2004-2024, identifying drug-event associations and temporal patterns.
Main Results:
- Identified 51,402 cases of antineoplastic-related cardiovascular toxicity among 18,289,374 reports.
- Revealed distinct class-specific patterns: anthracyclines (structural damage), immune checkpoint inhibitors (myocarditis), and fluoropyrimidines (vasospasm).
- Demonstrated critical temporal patterns: early-onset for fluoropyrimidines, intermediate for anthracyclines, and delayed for mitoxantrone. Cardiogenic shock had a 43.08% mortality rate.
Conclusions:
- This study reveals uncharacterized temporal and mechanistic patterns of antineoplastic cardiotoxicity.
- Provides an evidence-based framework for cardiovascular monitoring, highlighting critical intervention windows for specific drug classes.
- Supports the development of risk-stratified cardio-oncology protocols tailored to therapeutic classes.
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