Impact of probucol on xanthoma reduction and its role in cardiovascular event prevention in familial hypercholesterolemia patients

Although statins, ezetimibe, and PCSK9 inhibitors effectively reduce LDL-C levels and mitigate CHD risk, some residual risks persist. Probucol, a lipid-lowering agent with potent antioxidant properties, is prescribed in Asia for dyslipidemia treatment, ASCVD prevention, and xanthoma improvement. Its use was discontinued in Western countries due to concerns over HDL-C reduction and QT prolongation; however, recent research supports its therapeutic benefits. Probucol decreases HDL-C by promoting RCT through CETP and SR-BI activation while also enhancing HDL’s antioxidative function by elevating PON1 activity and lowering oxidized HDL levels. Studies on FH patients and those undergoing coronary revascularization indicate its role in secondary CV prevention. An integrated analysis of the PROSPECTIVE and IMPACT on IMT studies has suggested that, despite reducing HDL-C, probucol may offer protective effects against CHD. Potential applications of probucol for other diseases and recent advances of nanoparticle-based probucol delivery systems for the treatment of atherosclerosis and inflammation are also discussed.