Anti‐HER2 therapy–associated echocardiography‐related cardiac dysfunction and severe outcomes: Comparison of disproportionality and report‐level cluster analyses

Vollständiger Abstract

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Aims Conventional pharmacovigilance identifies drug–event reporting signals but not heterogeneity among anti‐HER2 cardiac dysfunction reports. We benchmarked this association using disproportionality analysis and assessed whether report‐level clustering added information beyond cardiovascular co‐reporting. Methods We analysed OpenVigil/FAERS data. A separate openFDA analysis estimated overall, individual‐drug and drug‐group reporting odds ratios (RORs) and proportional reporting ratios (PRRs). The clustering cohort comprised 589 unique reports, grouped by cardiovascular co‐reporting and clustered using Gower distance‐based partitioning around medoids. Severe outcome comprised death, hospitalization, life‐threatening events or disability. Multivariable logistic regression and a nested likelihood‐ratio test compared conventional and cluster‐based models. Results Echocardiography‐related cardiac dysfunction was disproportionately reported with anti‐HER2 therapies overall (ROR 26.64, 95% CI 25.61–27.71; PRR 25.95, 95% CI 24.97–26.96) and across evaluated drugs and groupings. Among 589 reports, 383 (65.0%) had dysfunction only and 206 (35.0%) had cardiovascular co‐reporting; severe outcomes occurred in 17.5% and 41.7%, respectively (adjusted OR 3.24, 95% CI 2.14–4.95). Five clusters were retained. The LV dysfunction with cardiovascular co‐reporting cluster had the highest severe outcome proportion (52.0%) and higher adjusted odds than the ADC‐associated EF‐decline cluster (adjusted OR 4.18, 95% CI 1.55–11.68). Adding the cluster term improved model fit (χ 2 = 11.34; p = 0.023). Conclusions Conventional analyses confirmed a strong anti‐HER2 reporting signal and an association between cardiovascular co‐reporting and severe outcomes. The retained clusters added complementary report‐level resolution without constituting a validated clinical classification or prediction tool.