Comparative Cardiotoxicity Profiles Across Antineoplastic Therapeutic Classes: A Global Analysis Using WHO VigiAccess

Background/Objectives: Antineoplastic therapies have improved cancer survival but remain a major source of treatment-related cardiotoxicity. Comparative global pharmacovigilance evidence across anthracyclines, anti-HER2, and anti-VEGF therapies remains limited. Methods: A retrospective disproportionality study was conducted using Individual Case Safety Reports (ICSR) from the World Health Organization (WHO) VigiBase accessed via VigiAccess (March 23, 2026). Eight antineoplastic agents were grouped into three therapeutic classes. Descriptive analyses of demographic characteristics, System Organ Class (SOC) distributions, and cardiac Preferred Terms (PT) were performed. Reporting Odds Ratios (ROR) with 95% confidence intervals were calculated using a restricted antineoplastic comparator cohort. Signals were defined as ROR lower 95% CI >1 with ≥5 cases. Results: A total of 388,068 ICSR were analyzed. Anti-HER2 agents showed the highest relative cardiotoxic burden (10.43%) and the strongest disproportionality signal (ROR 1.91; trastuzumab ROR 2.11). Anthracyclines accounted for the largest number of cardiac reports (n = 11,273), with a predominantly structural-myocardial phenotype led by cardiomyopathy and heart failure. Anti-VEGF agents displayed a distinct vascular–ischemic profile, with redistribution toward vascular (10.86%) and renal (6.08%) SOCs and myocardial infarction as a dominant cardiac PT. Conclusions: Cardiotoxicity associated with antineoplastic therapy follows class-specific phenotypic patterns rather than a uniform profile. Anti-HER2 agents concentrate the highest relative burden, anthracyclines the greatest absolute volume, and anti-VEGF therapies exhibit a distinct vascular–ischemic phenotype. These findings support mechanism informed, class-specific cardiovascular surveillance strategies and highlight the value of global pharmacovigilance data.