Lowering LDL cholesterol, but not raising LDL receptor activity, by ezetimibe

► Ezetimibe-plus-statin therapy enhances low-density lipoprotein (LDL) receptor activity.
► It is still unclear whether ezetimibe alone enhances LDL receptor activity.
► Patients with hypercholesterolemia were treated with ezetimibe for 4 months.
► LDL receptor activities were estimated with the equation during the therapy.
► Ezetimibe lowered LDL cholesterol without raising LDL receptor activity.

BackgroundEzetimibe, an inhibitor of intestinal cholesterol absorption, is effective in lowering serum low-density lipoprotein (LDL) cholesterol with or without coadministration of statin. Ezetimibe-plus-statin therapy enhances LDL receptor activity, but it is still unclear whether ezetimibe alone enhances LDL receptor activity, resulting in LDL cholesterol decrease.ObjectiveWe investigated whether ezetimibe lowers serum LDL cholesterol by raising LDL receptor activity in humans.MethodsPatients with hypercholesterolemia (n = 28; age [mean ± SD], 61.6 ± 13.0 years; 57% men) were treated with ezetimibe (10 mg/d) for 4 months. Before and after the treatment, serum LDL cholesterol, apolipoprotein B (apo B), and apolipoprotein C-II (apo C-II) were measured. LDL receptor activities were estimated with the equation we reported previously as follows: LDL receptor activity (represented as a percentage of normocholesterolemic subjects) = 63.595 + apo C-II (in mg/dL) × 13.459−apo B (in mg/dL) × 0.366.ResultsBy the treatment of ezetimibe, LDL cholesterol (176.8 ± 17.9 vs 138.0 ± 19.7 mg/dL) was lowered 21.9% significantly (P < .01). The estimated LDL receptor activities before and after the ezetimibe treatment were 86.8% ± 21.4% and 89.6% ± 19.7%, respectively, with no significant difference between them (P = .13).ConclusionEzetimibe lowered LDL cholesterol significantly in patients with hypercholesterolemia without raising LDL receptor activity. The enhancement of LDL receptor activity is less involved in the pharmacologic action of ezetimibe.