Gender and age disparities in cardiac immune-related adverse events associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the FAERS database

Objectives The cardiotoxicity of immune checkpoint inhibitors (ICIs) has garnered significant clinical attention due to its high mortality rate. However, limited clinical research and inconsistent results have hindered a comprehensive understanding of this issue. This study seeks to elucidate gender and age differences in cardiac-related adverse reactions, aiming to offer scientific evidence to inform clinical practice.Design A retrospective pharmacovigilance study.Setting Based on the reports of ICIs in the FDA Adverse Event Reporting System database from 2003-2023, we conducted a disproportionality analysis to identify cardiac immune-related adverse events (irAEs) and explored the correlation of age and gender with these adverse events.Main outcome measures The main cardiac irAEs were defined by four preferred terms: myocarditis, atrial fibrillation, cardiac failure and pericardial effusion. Both the proportional reporting ratio (PRR) and reporting odds ratio (ROR) are frequency methods. Data mining was performed using the PRR method, which assesses the relative risk of adverse drug reactions by comparing the frequency of reports associating a specific drug with a particular adverse reaction to the frequency of reports linking any drug to the same reaction. A higher PRR indicates a more robust adverse event signal, suggesting a stronger statistical association between the drug of interest and the target adverse event. In the research process, we primarily used the ROR and PRR from disproportionality analysis to screen for cardiac irAEs, while also elucidating the correlation between these reactions and factors such as age and gender.Results A total of 2033 adverse events were retrieved, and myocarditis was the most common cardiac irAEs. Gender disparities exist in the incidence of various adverse reactions to the same medication. Female patients need to be particularly vigilant for cardiac adverse events when taking atezolizumab, and male patients should be especially cautious for cardiac adverse events when using ipilimumab. Furthermore, ipilimumab produced a positive signal for pericardial effusion in the elderly group but not in the younger group, suggesting that elderly patients may be more susceptible to adverse reactions. Therefore, increased vigilance and careful monitoring are warranted during clinical administration of this medication to elderly patients.Conclusion Our study highlights the gender and age differences in cardiac adverse events with ICIs, providing valuable insights for clinical application.