Long-Term Administration of Multikinase Inhibitors Is a Potential Risk Factor for Atherosclerosis in Patients with
Nao Muraoka1, Takuya Oyakawa1, Ayano Fujita1
1Division of Cardio-Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
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.
Insights
Long-term use of multikinase inhibitors (MKIs) in thyroid cancer patients significantly increases atherosclerosis risk, independent of other factors. Monitoring for cardiovascular complications is crucial during MKI therapy.
Area of Science:
- Cardiovascular Research
- Oncology
- Pharmacology
Background:
- Vascular endothelial growth factor inhibitors (VEGFIs) are vital cancer treatments inhibiting angiogenesis.
- VEGFIs may promote atherosclerosis in normal vessels, but clinical significance remains unclear.
- This study investigates atherosclerosis development with long-term multikinase inhibitor (MKI) use.
Purpose of the Study:
- To determine if long-term multikinase inhibitor (MKI) administration promotes atherosclerosis in thyroid cancer patients.
- To assess the association between MKI use and the appearance of new atherosclerotic plaques.
- To evaluate the incidence of major adverse cardiac events (MACE) in MKI-treated patients.
Main Methods:
- Retrospective analysis of 63 thyroid cancer patients, comparing 39 on long-term MKIs (>1 year) with 24 controls.
- Computed tomography (CT) scans were used to assess vessel walls and new plaque formation.
- Medical records were reviewed for new-onset MACE during the observation period.
Main Results:
- New atherosclerotic plaques developed in 44% of MKI patients versus 0% in controls over a median 43-month follow-up.
- MKI administration was the sole independent predictor of new plaque appearance.
- The carotid artery was the most common site for new plaques; two MKI patients experienced MACE.
Conclusions:
- Multikinase inhibitor (MKI) administration appears to be an independent risk factor for atherosclerosis in thyroid cancer patients.
- Long-term MKI therapy necessitates monitoring for atherosclerosis and related cardiovascular complications.
- Further research is warranted to elucidate the precise mechanisms and clinical impact.
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