Risk factors and comorbidities of immune checkpoint inhibitor-associated myocarditis

Background Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy but can trigger rare but fatal immune-related adverse events like myocarditis. Despite its clinical significance, the risk factors and comorbidity profiles predisposing patients to ICI-associated myocarditis remain incomplete, and data on sex-based differences in cardiovascular outcomes are limited. Purpose This study aims to identify risk factors for ICI-associated myocarditis and assess sex-based differences in cardiovascular outcomes. Methods This retrospective cohort study used TriNetX to identify patients started on ICIs from January 2015 to October 2024, with myocarditis onset within 3 months. Demographics, ICI types, malignancies, and comorbidities were compared between the myocarditis and non-myocarditis groups. Propensity-score matching by sex was performed within the myocarditis group to assess 6-month major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, or cardiac arrest, using the Cox hazards model. Results Of 133,600 ICI-treated patients, 477 developed myocarditis. These patients were older, more often male, predominantly White, and had higher rates of heart failure, ischemic heart disease, chronic kidney disease, and diabetes. Ipilimumab (25% vs 8%) and nivolumab (43% vs 29%) were more common in myocarditis cases. No significant difference in 6-month MACE between males and females was observed (HR 1.382, 95% CI 0.829–2.304). Conclusion ICI-associated myocarditis is more common in older, White, male patients with cardiovascular/metabolic comorbidities, especially with ipilimumab or nivolumab use. Sex did not affect MACE outcomes. Further studies are needed to improve risk stratification and management.