New Horizons for Probucol, an Old, Mysterious Drug

[See article vol.28 : 124-136] Intensive low-density lipoprotein (LDL)-lowering therapies involving statins, intestinal cholesterol transporter inhibitor (ezetimibe), and proprotein convertase subtilisin/kexin type 9 inhibitors are associated with a significantly lower number of atherosclerotic cardiovascular events. However, these events have not been completely prevented to date. Therefore, additional pharmacological interventions may be crucial to mitigate "residual risks" other than serum LDL cholesterol (LDL-C) levels. Probucol was developed as an anti-oxidative compound to prevent the degradation of tire rubber and later applied to reduce serum LDL-C levels in patients with hypercholesterolemia. The effect of probucol on the reduction of serum LDL-C levels was not substantial ; however, probucol has been widely used in Japan before the launch of statins, particularly in patients with familial hypercholesterolemia (FH). Japanese researchers have demonstrated that probucol reduces LDL-C levels even in Watanabe heritable hyperlipidemic (WHHL) rabbits and in patients with homozygous and heterozygous FH and LDL receptor (LDL-R) deficiency via an enhanced catabolism of LDL independent of LDL-R and increased cholesterol excretion into the bile.