Exploration of preventive drugs for sunitinib-induced heart failure utilizing large-scale medical database

• Published in: Proceedings for Annual Meeting of The Japanese Pharmacological Society Vol. 95; p. 1-SS-35
• Main Authors: Yoshika, Sakamoto, Tomochika, Nanami, Hamano, Hirofumi, Goda, Mitsuhiro, Niimura, Takahiro, Aizawa, Fuka, Yagi, Kenta, Nakamura, Akihito, Nishiuchi, Shiori, Izawa-Ishizawa, Yuki, Zamami, Yoshito, Ishizawa, Keisuke
• Format: Journal Article
• Language: Japanese; English
• Published: Japanese Pharmacological Society 2022
• ISSN: 2435-4953; 2435-4953
• DOI: 10.1254/jpssuppl.95.0_1-SS-35

BACKGROUND: Several studies have reported that patients treated with sunitinib, a tyrosine kinase inhibitor, have developed left ventricular dysfunction and heart failure, but there is currently no treatment for heart failure with sunitinib. The purpose of the present study is to identify candidate drugs for the treatment of sunitinib-induced heart failure using a large medical database. METHOD: We analyzed the FDA Adverse Event Reporting System (FAERS) and the WHO global adverse event reporting database (VigiBase) to find candidate drugs for prevention of sunitinib-induced heart failure. The effects of the candidate drugs on cell viability and cell morphology were evaluated using the WST-8 assay and immunostaining in H9c2 cells derived from rat cardiac rhabdomeres. RESULTS: FAERS and VigiBase searches revealed significantly higher reporting odds ratio (ROR) of heart failure in patients treated with sunitinib than in those not treated with sunitinib. The ROR was reduced by concomitant use of Vitamin D (FAERS: ROR 0.50, 95% CI 0.26-0.96; VigiBase: ROR 0.37, 95% CI 0.10-0.95). In vitro, Vitamin D significantly improved the viability and maintained the cell morphology in H9c2 cells exposed to sunitinib. CONCLUSION: The findings suggest the potential value of Vitamin D in preventing sunitinib-induced heart failure.