| アブストラクト | OBJECTIVES: Immune checkpoint inhibitors (ICIs) are increasingly used in cancer therapy; however, systematic epidemiological studies of ICI-associated cardiovascular adverse events in China remain limited. This study aims to analyze cardiovascular adverse event signals associated with ICIs approved by the Food and Drug Administration (FDA), thereby providing evidence to support safer clinical use. METHODS: Data were obtained from the Food and Drug Administration Adverse Event Reporting System (FAERS) database from the first quarter of 2011 to the fourth quarter of 2024 (56 quarters over 14 years). Adverse event reports were screened using "primary suspected drugs" as the inclusion criterion. Eight ICIs were included: atezolizumab, avelumab, durvalumab, nivolumab, pembrolizumab, cemiplimab, ipilimumab, and tremelimumab. Adverse events were first classified according to system organ class (SOC), and reports involving cardiac and vascular disorders were extracted. Signal detection was subsequently performed at both the standardized MedDRA query (SMQ) level and preferred terms (PT) level. The Bayesian confidence propagation neural network (BCPNN) method was applied to calculate the information component (IC) and its 95% confidence interval (CI) for each target drug-adverse event pair. Positive signals of immune-related cardiovascular adverse events (irCVEs) were defined as reports >/=3 and a lower limit of the 95% CI of IC (IC(025)) >0. RESULTS: A total of 12 890 cardiac adverse event reports and 8 543 vascular adverse event reports were identified. Among all cardiovascular adverse event reports, the top three drugs were nivolumab, pembrolizumab, and atezolizumab. Male patients accounted for a higher proportion than female patients, and patients aged over 65 years represented more than 50.00% of reports. From 2011 to 2024, the number of cardiovascular adverse event reports associated with the 8 ICIs showed a rapid upward trend. The proportions of fatal outcomes were 30.74% for cardiac adverse events and 20.83% for vascular adverse events. At the SMQ level, positive cardiac adverse event signals involved 6 SMQ codes, whereas positive vascular adverse events signals involved 8 SMQ codes. Non-infectious myocarditis/pericarditis was the only strong positive signal shared by all 8 ICIs, followed by thrombophlebitis, vasculitis, and cardiac arrhythmias. At the PT level, 47 positive cardiac adverse event signals and 36 positive vascular adverse event signals were detected. Strong positive cardiovascular adverse event signals included myocarditis, immune-mediated myocarditis, autoimmune myocarditis, pericardial effusion, cardiac tamponade, malignant pericarditis, embolism, and thrombophlebitis migrans, etc. CONCLUSIONS: Cardiovascular adverse events associated with ICIs in the FAERS database commonly include myocarditis, pericarditis, arrhythmias, and vasculitis, with relatively high proportions of severe outcomes and mortality. Therefore, pre-treatment risk screening, close monitoring during therapy, and multidisciplinary management of cardiovascular adverse events are essential to ensure patient safety. |
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| 組織名 | Office of Pharmacovigilance, Third Affiliated Hospital of Sun Yat-sen University,;Guangzhou 510630. 237211063@csu.edu.cn.;Guangzhou 510630. quch@mail.sysu.edu.cn.;Guangzhou 510630.;Department of Pharmacology, Xiangya School of Pharmaceutical Sciences, Central;South University, Changsha 410013.;Information Center, Third Affiliated Hospital of Sun Yat-sen University,;Guangzhou 510630, China. |
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