A Real-World Pharmacovigilance Analysis of HER2 Inhibitor-Induced Cardiovascular Toxicity

INTRODUCTION: With the widespread use of human epidermal growth factor receptor 2 (HER2) inhibitors in cancer treatment, cardiovascular diseases induced by these agents have become a significant adverse event. METHODS: We retrieved reports of HER2 inhibitor-induced cardiovascular adverse events (CVAEs) from the FDA Adverse Event Reporting System(FAERS) database, covering the period from the first quarter of 2004 to the fourth quarter of 2024. Disproportionality analyses were conducted using reporting odds ratios and proportional reporting ratios. The signals of HER2 inhibitor-related CVAEs were evaluated at both the standardized MedDRA query and preferred term levels. RESULTS: A total of 12,698 reports associated with CVAEs were identified, with HER2 inhibitors listed as the primary suspected drug, involving 12,398 patients. Most cases were observed in individuals aged 45 years and older, with a notably higher proportion in women. The time to onset of HER2 inhibitor-induced CVAEs showed certain variability. Trastuzumab exhibited higher cardiovascular toxicity compared with other HER2 inhibitors. In general, monoclonal antibodies demonstrated greater cardiovascular toxicity, whereas antibody-drug conjugates and HER2-tyrosine kinase inhibitors displayed comparable and lower effects. CONCLUSION: This pharmacovigilance analysis reveals a strong association between HER2 inhibitors and CVAEs, providing valuable insights for their prevention and clinical management.