Effects of probucol on xanthomata regression in familial hypercholesterolemia.

Fifty-one patients with familial hypercholesterolemia were treated for 2 to 4 years with probucol, cholestyramine, clofibrate and compactin in various combinations. Mean baseline serum cholesterol was 359 +/- 10 mg/dl in the heterozygote, and 582 +/- 52 mg/dl in the homozygote patients. We found that a combination of probucol, cholestyramine and compactin decreased serum cholesterol to normal or near normal in most of the heterozygote patients. In 3 severely affected heterozygote and all 8 homozygote patients, adequate cholesterol reduction was only possible with plasmapheresis plus a hypolipidemic agent. Measurement of the Achilles tendon after 12 to 16 months of treatment showed that reductions in thickness occurred in all patients taking probucol, even in a single-drug regimen, in those undergoing plasmapheresis, especially if probucol was used and in those receiving a combination of cholestyramine and compactin. Probucol was most effective in patients who experienced the greatest decreases in high density lipoprotein (HDL) levels, whereas the cholestyramine-compactin combination worked without decreasing HDL concentrations. Combined clofibrate-cholestyramine therapy, by contrast, led to increased tendon thickness in all but 1 patient. It is believed that probucol exerts its positive effect on xanthomata regression by reducing the size of HDL particles, as was shown in this study. It has already been reported that smaller HDL particles are more active in reverse cholesterol transport. The direct peripheral action of probucol may have aided regression as well.