Cardiovascular safety profile of CTLA-4: a pharmacovigilance analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS)

Background Cardiovascular adverse events (CVEs) associated with the two drugs, ipilimumab and tremelimumab, were extracted from the US Adverse Event Reporting System (FAERS) to ensure their safe clinical use. Methods Adverse event reports related to ipilimumab and tremelimumab in FAERS from January 1, 2004, to December 31, 2024, were collected. Outcomes were standardized and classified using the Standardized Medical Dictionary for Regulatory Activity Questions (SMQ). Outcomes of interest (supraventricular tachyarrhythmia, embolic and thrombotic events of unspecified vascular type with mixed arteriovenous involvement, venous embolism and thrombotic events, arterial embolism and thrombotic events, myocardial infarction,non-infectious myocarditis/pericarditis, ischemic cerebrovascular diseases,shock-related circulatory/cardiac disorders (excluding torsade de pointes), heart failure, hypertension) were analyzed using the Reported Odds Ratio method. Results The number of CVEs reported for ipilimumab and tremelimumab was 2344. Among the 10 SMQs we selected, the relevant SMQs with suspicious signals in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) were venous thrombosis and thrombotic events, as well as non-infectious myocarditis/pericarditis. In ipilimumab, the relevant SMQs with suspicious signals were supraventricular tachycardia, venous thrombosis and thrombotic events, and non-infectious myocarditis/pericarditis. In tremelimumab, the relevant SMQs with suspicious signals were only hypertension. Conclusion Current pharmacovigilance studies have identified potential signals of an increased incidence of CVEs caused by CTLA-4 drugs, which often results in serious consequences.