Pre-Existing Cardiovascular Conditions as Clinical Predictors of Myocarditis Reporting with Immune Checkpoint Inhibitors: A VigiBase Study

SIMPLE SUMMARY: Up to 50% of myocarditis events developed in cancer patients upon treatment with immune checkpoint inhibitors (ICIs) are fatal. Therefore, identification of clinical risk factors predicting myocarditis onset during treatment with ICIs is important for the purpose of cardiac surveillance of high-risk patients. The aim of this retrospective matched case-control study was to assess whether pre-existing cardiovascular conditions were associated with the reporting of myocarditis with ICIs in VigiBase, the World Health Organization global database of suspected adverse drug reactions. Taking drugs labelled for the treatment of cardiovascular conditions as a proxy for concomitant cardiovascular risk factors and/or cardiovascular diseases, we found an association of moderate size between pre-existing cardiovascular conditions and the reporting of myocarditis with ICIs. Future prospective pharmacoepidemiological studies should assess the causal relationship between pre-existing cardiovascular conditions and myocarditis onset in a cohort of cancer patients followed during treatment with ICIs. ABSTRACT: Although rare, immune checkpoint inhibitor (ICI)-related myocarditis can be life-threatening, even fatal. In view of increased ICI prescription, identification of clinical risk factors for ICI-related myocarditis is of primary importance. This study aimed to assess whether pre-existing cardiovascular (CV) patient conditions are associated with the reporting of ICI-related myocarditis in VigiBase, the WHO global database of suspected adverse drug reactions (ADRs). In a (retrospective) matched case-control study, 108 cases of ICI-related myocarditis and 108 controls of ICI-related ADRs other than myocarditis were selected from VigiBase. Drugs labeled as treatment for CV conditions (used as a proxy for concomitant CV risk factors and/or CV diseases) were found to be associated more strongly with the reporting of ICI-related myocarditis than with other ICI-related ADRs (McNemar’s chi-square test of marginal homogeneity: p = 0.026, Cramer’s coefficient of effect size: Φ = 0.214). No significant association was found between pre-existing diabetes and ICI-related myocarditis reporting (McNemar’s test of marginal homogeneity: p = 0.752). These findings offer an invitation for future prospective pharmacoepidemiological studies to assess the causal relationship between pre-existing CV conditions and myocarditis onset in a cohort of cancer patients followed during ICI treatment.