Cardiac adverse events associated with dual immune checkpoint inhibitors: a pharmacovigilance analysis from the FDA adverse event reporting system

Abstract

Aims: Immune-related adverse events(irAEs) are common among cancer patients receiving dual immune checkpoint inhibitors (ICI). Cardiac adverse events rank among the most severe categories of such reactions. This study aims to investigate the characteristics and influencing factors of cardiac adverse events associated with dual ICIs.

Methods and results: We collected data on cardiac adverse events associated to dual ICIs from the US Food and Drug Administration Adverse Event Reporting System database (FAERS), covering the period from the first quarter of 2015 to the fourth quarter of 2024. A disproportionality analysis was performed to assess the association between different dual ICIs and cardiac adverse events, and a comprehensive study was conducted to identify potential influencing factors. Cardiac adverse events accounted for 7.5% of all ICI adverse event reports in the FAERS database. Nivolumab plus ipilimumab was associated with the highest number of significant preferred term (PT) signals, while durvalumab plus tremelimumab had the highest percentage of life-threatening outcomes. The median onset time for cardiac adverse events following dual ICIs therapy was 32 days (IQR 15-77). Myositis and myasthenia gravis were the most commonly co-reported extracardiac conditions in myocarditis cases, whereas complete atrioventricular block and cardiogenic shock were the most frequently reported intracardiac complications. Older patients, males, and those with kidney cancer were at higher risk of developing cardiac adverse events.

Conclusion: This study identified distinct associations between different dual ICIs treatment strategies and various cardiac adverse events. We further identified potential risk factors and co-reported symptoms of cardiotoxicity, which may aid in the early diagnosis and monitoring of ICI-associated cardiac adverse events.

Keywords: Cardiac adverse events; FAERS database; Immune-associated adverse events; Pharmacovigilance; dual Immune checkpoint inhibitors.