Abstract 4373293: Immune Checkpoint Inhibitor Thyroid Dysfunction is Associated with Increased Incidence of Coronary Artery Disease and Arrhythmia

Abstract

Introduction: Immune checkpoint inhibitor (ICI) induced hypothyroidism is a common immune related adverse event during cancer immunotherapy, but the association with cardiovascular (CV) risk is unknown. Methods: All patients receiving ICI therapy for solid organ malignancy from 2015-2023 at a single academic center were identified (n~6000), and an algorithm designed to detect ICI-associated thyroid dysfunction (ICI-TD) was developed using thyroid stimulating hormone labs and thyroid hormone replacement medications. Sensitivity and specificity were assessed using clinician diagnosis as the gold standard. Cancer types and CV events were identified using ICD codes. Chi-Squared was used where appropriate, and univariate logistic regression was used to assess the likelihood of each CV outcome, with results visualized on a forest plot. Kaplan-Meier curves were generated to illustrate the time to onset of cardiac events in ICI-TD and Non-ICI-TD populations. Results: The algorithm (Figure 1A) was found to have a sensitivity of 92% and a specificity of 93% to detection of ICI-TD. Among patients receiving ICI therapy with normal thyroid function prior to their first dose of ICI therapy (Baseline Population; n=4720), ICI-TD was observed in 795 (16.8%) patients with significant variation across cancer types (p<0.001). Compared against those without ICI-TD (n=3925), coronary artery disease (CAD) (9.75% vs 5.36%, p<0.001) and arrhythmias (8.78% vs 6.51%, p=0.03) were associated with ICI-TD (Figure 1B). Heart failure, acute coronary syndrome, myocarditis, and pericarditis were not associated with ICI-TD. There were no significant differences in the time to onset of arrhythmias (p=0.22) or CAD (p=0.21) between patients with ICI-TD and those without (Figures 1C and 1D). Conclusion(s): An algorithm can detect ICI-TD with high sensitivity and specificity. ICI-TD is associated with long term risk of CAD and arrhythmia, highlighting a high-risk group that may benefit from increased CV monitoring and risk modification.