Long-Term Administration of Multikinase Inhibitors Is a Potential Risk Factor for Atherosclerosis in Patients with Thyroid Cancer.

INTRODUCTION: Vascular endothelial growth factor inhibitors are key drugs for cancer treatment as they inhibit angiogenesis. However, they also promote atherosclerosis in normal vessels, though the clinical relevance of this phenomenon is unreported. In this study, we investigated whether long-term multikinase inhibitor (MKI) administration is associated with incident atherosclerosis. METHODS: We evaluated 63 patients with thyroid cancer; 39 patients received MKIs for more than 1 year (MKI group) and 24 had never received MKIs and underwent computed tomography (CT) follow-up (non-MKI group). Using medical records, we retrospectively observed vessel walls on CT scans and investigated the appearance of new plaques. We also studied all new-onset major adverse cardiac events (MACE; cardiac death, nonfatal myocardial infarction, worsening of angina, coronary revascularization, and acute heart failure) that occurred during the observation period in both groups. RESULTS: The median observation period for the Kaplan-Meier curve for new plaques was 43 months. New plaques appeared in significantly more patients in the MKI group (44%) than in the non-MKI group (0%). A multivariate analysis revealed that only MKI administration correlated with new plaque appearance. A history of hypertension, diabetes mellitus, or statin administration was not significantly associated with new plaque appearance. The carotid artery was the predominant site for new plaques. Two patients in the MKI group and none in the non-MKI group developed MACE. CONCLUSION: MKI administration may be an independent risk factor for atherosclerosis in patients with thyroid cancer. Complications associated with atherosclerotic disease should be monitored during long-term MKI administration.