Comparative Cardiac Adverse-Event Reporting Patterns 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. Previous pharmacovigilance studies have largely focused on drug-specific cardiac signals or individual therapeutic pathways, whereas cross-class differences in cardiovascular reporting across MedDRA categories and their impact on disproportionality estimates remain less well characterized. We therefore compared cardiac adverse-event reporting patterns across anthracyclines, anti-HER2 agents, and anti-VEGF agents within a restricted antineoplastic comparator cohort. Methods: A retrospective pharmacovigilance study was conducted using aggregated ICSR data from VigiBase accessed through the public VigiAccess interface (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 a lower 95% CI bound >1 with at least five cardiac reports. Results: Across eight drug-specific VigiAccess queries, 389,068 drug-specific report observations were analyzed. Anti-HER2 agents showed the highest proportional cardiac-reporting burden (10.43%) and the strongest class-level disproportionality signal (ROR 2.04; 95% CI: 1.99–2.10), with trastuzumab showing the strongest individual-drug estimate (ROR 2.22; 95% CI: 2.16–2.29). Anthracyclines accounted for the largest number of cardiac reports (n = 11,273), with a reporting pattern dominated by myocardial-dysfunction Preferred Terms, led by cardiomyopathy and heart failure. Anti-VEGF agents showed greater reporting within the Vascular disorders (10.86%) and Renal and urinary disorders (6.08%) SOCs, with myocardial infarction among the most frequently reported cardiac PTs. Conclusions: Cardiac adverse event reporting for antineoplastic therapy follows class-specific patterns rather than a uniform profile. Anti-HER2 agents showed the highest proportion of reports classified under Cardiac disorders, anthracyclines the greatest absolute volume, and anti-VEGF therapies exhibited a distinct vascular–ischemic reporting profile. These reporting-based signals may support hypotheses regarding class-specific cardiovascular surveillance consistent with established cardio-oncology guidance, while highlighting both the value and the inherent limitations of global spontaneous-reporting pharmacovigilance data. These findings are hypothesis-generating and should be interpreted as reporting patterns rather than incidence estimates, comparative clinical risks, or causal effects. Spontaneous-reporting data remain susceptible to reporting bias, unmeasured confounding, and incomplete clinical information.