The Impact of Statins on the Survival of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib or Lenvatinib
Open Access
Abstract
We aimed to evaluate the survival benefits of coadministering statins and multityrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC). Data from the Health Insurance Review and Assessment Service in Korea (2010–2020) were utilized. Statin use (≥28 cumulative defined daily doses) was analyzed, with 1534 statin users matched to 6136 non-users (1:4 ratio) using propensity scores. Primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS). Statin use significantly improved OS (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.72–0.82, p < 0.001) and PFS (HR 0.78, 95% CI 0.74–0.84, p < 0.001). Continuous or post-TKI statin users had better OS, while discontinuation after TKI use led to poorer OS. Both lipophilic and hydrophilic statins improved OS and PFS, particularly with ≥730 cumulative defined daily doses. In conclusion, combining statins and TKIs in patients with advanced HCC yielded significant survival benefits, influenced by statin dosage and duration. Continuous statin administration post-TKI treatment is crucial for improving outcomes in patients with HCC.Keywords
Funding Information
- Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) (HR22C1734, HR21C1003, NRF-2021R1C1C1009619, NRF-2022R1H1A2093189, 2022R1A2C2092422)
- Bio and Medical Technology Development Program of the National Research Foundation (HR22C1734, HR21C1003, NRF-2021R1C1C1009619, NRF-2022R1H1A2093189, 2022R1A2C2092422)
This publication has 52 references indexed in Scilit:
- Chemopreventive strategies in hepatocellular carcinomaNature Reviews Gastroenterology & Hepatology, 2013
- Statin use and risk of hepatocellular carcinomaEuropean Journal of Epidemiology, 2013
- Sorafenib Inhibits Hypoxia-Inducible Factor-1α Synthesis: Implications for Antiangiogenic Activity in Hepatocellular CarcinomaClinical Cancer Research, 2012
- Statin inhibits hypoxia-induced endothelin-1 via accelerated degradation of HIF-1α in vascular smooth muscle cellsCardiovascular Research, 2012
- Hepatotoxicity associated with statins: Reports of idiosyncratic liver injury post-marketingJournal of Hepatology, 2012
- Pravastatin inhibits cell proliferation and increased MAT1A expression in hepatocarcinoma cells and in vivo modelsCancer Cell International, 2012
- Activation of Phosphatidylinositol 3-Kinase/Akt Signaling Pathway Mediates Acquired Resistance to Sorafenib in Hepatocellular Carcinoma CellsThe Journal of Pharmacology and Experimental Therapeutics, 2011
- AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1Nature Cell Biology, 2011
- AMPK as a therapeutic target in renal cell carcinomaCancer Biology & Therapy, 2010
- Sorafenib in Advanced Hepatocellular CarcinomaNew England Journal of Medicine, 2008