Signals of pericardial and myocardial events associated with antiangiogenic drugs: a disproportionality analysis on FAERS®.

PURPOSE: Antiangiogenic drugs (AADs) are an heterogenous group of molecules widely used in the treatment of cancers. Based on their mechanism of action, AADs are associated with an increased reporting of cardiovascular adverse events (AEs). However, pericarditis, pericardial effusion and myocarditis were not documented for most of AADs. The aim of this study was to determine whether AADs may be associated with pericarditis, pericardial effusion and myocarditis in a real-world setting. METHODS: We performed an extensive descriptive and disproportionality analysis of pericarditis, pericardial effusion and myocarditis AEs related to AADs on the FDA Adverse Event Reporting System (FAERS) database, using the reporting odds ratio (ROR) as a measure of emerging safety signal. RESULTS: Statistically significant signals of pericardial effusion and myocarditis were found for AADs compared to all other drugs in the database. The RORs for the pooled AADs were 2.37 [(95% CI (2.17–2.59)] for pericardial effusion and 2.26 [95% CI (1.99–2.58)] for myocarditis. In the sub-analysis performed for single AADs, an emerging disproportionality safety signal has been identified for ponatinib for pericarditis, vandetanib, sunitinib, ponatinib, pazopanib, nintedanib, cabozantinib, axitinib, and bevacizumab for pericardial effusion, and regorafenib, lenvatinib, cabozantinib, axitinib and bevacizumab for myocarditis. However, when compared with other anticancer agents to contextualize the risk within oncologic therapies, no overall disproportionality signals were detected, except for pericardial effusion with ponatinib and vandetanib, and myocarditis with lenvatinib. CONCLUSION: Our results show that most AADs were associated with signals of disproportionate reporting of pericardial and myocardial AEs when compared to all drugs in the database, which may be related to their different pharmacological angiogenic targets. Of note, signals persisted for pericardial effusion with vandetanib and ponatinib, and for myocarditis with lenvatinib. These findings highlight potential safety signals of public health relevance, while underlining the importance of therapeutic-context analyses to better characterize cardiovascular risk associated with AADs. Further pharmacovigilance studies are needed to expand knowledge and better characterize the cardiovascular safety profile of the different AADs.