Abstract 9703: Lowering LDL Cholesterol, but not Raising LDL Receptor Activity, by Ezetimibe

Abstract

Introduction: Ezetimibe, an inhibitor of intestinal cholesterol absorption, is effective in lowering serum low-density lipoprotein (LDL) cholesterol with or without co-administration 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. Hypothesis: We assessed the hypothesis that ezetimibe lowers serum LDL cholesterol by raising LDL receptor activity in humans.

Methods: Hypercholesterolemic patients (n = 28; age 61.3 ± 12.7 (mean ± SD); 57% male) were treated with ezetimibe (10 mg/day) for 4 months. Before and after the treatment, serum LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride were measured. Serum apolipoprotein A-I (apo A-I), B (apo B), and C-II (apo C-II) were also measured and the estimated LDL receptor activities were calculated by our previously reported methods as follows: LDL receptor activity (expressed as a percentage of normocholesterolemic subjects) = 63.6 + apo C-II (mg/dl) x 13.5 - apo B (mg/dl) x 0.37.

Results: By the treatment of ezetimibe, LDL cholesterol (178.5 ± 26.2 vs. 141.1 ± 26.2 mg/dl, p < 0.01) was lowered 21% significantly and HDL cholesterol (56.1 ± 12.3 vs. 59.5 ± 16.2 mg/dl, p < 0.01) was increased 6% significantly. Triglyceride (184.4 ± 85.6 vs.174.8 ± 85.2 mg/dl, p = 0.60) was not changed. Serum apo B (136.2 ± 24.5 vs. 113.0 ± 23.8 mg/dl, p < 0.01) was lowered 17% significantly and apo A-I (143.5 ± 28.5 vs. 150.3 ± 31.9 mg/dl, p < 0.01) was increased 5% significantly. Apo C-II (5.9 ± 2.2 vs. 5.5 ± 2.2 mg/dl, p = 0.11) was not changed. The estimated LDL receptor activities before and after the ezetimibe treatment were 93.5 ± 25.1% and 96.9 ± 24.4%, respectively with no significant difference between them (p = 0.14).

Conclusions: Ezetimibe lowered LDL cholesterol 21% significantly in hypercholesterolemic patients without raising LDL receptor activity. In conclusion, the enhancement of LDL receptor activity is suggested to be less involved in the pharmacological action of ezetimibe.