Effect of Ezetimibe Monotherapy on Low-Density Lipoprotein Cholesterol and on Markers of Cholesterol Synthesis and Absorption in Japanese Patients With Hypercholesterolemia

BACKGROUND The aim of this study was to evaluate effect of ezetimibe monotherapy on serum low-density lipoprotein cholesterol (LDL-C) in Japanese patients and to investigate the association between changes of LDL-C and changes of markers for cholesterol synthesis and absorption. METHODS Seventy-six hypercholesterolemic patients without statin therapy were enrolled and randomized to two groups, which were an ezetimibe group (group E, n = 44) and a control group without ezetimibe treatment that received diet therapy alone (group C, n = 32). The study period was 12 weeks. In group E, 10 mg of ezetimibe was administered daily after breakfast. Serum lipids were measured every 4 weeks, while lathosterol (a cholesterol synthesis marker) and campesterol and sitosterol (cholesterol absorption markers) were examined at baseline and at 12 weeks. RESULTS A significant reduction of LDL-C was observed in group E at both 4 and 12 weeks (from 155 ± 3.9 to 128 ± 3.4 mg/dL and 132 ± 3.9 mg/dL, respectively, both P < 0.01), associated with an increase of high-density lipoprotein cholesterol (HDL-C)at 12 weeks (from 53 ± 1.3 to 55 ± 1.5 mg/dL, P < 0.05) and no change of triglycerides. In contrast, none of these lipids changed in group C. An increase of lathosterol and a decrease of campesterol and sitosterol were observed in group E, while none of these markers changed in group C. When group E was divided into two subgroups according to the reduction of LDL-C, which were a good response group (reduction ≥ 20 mg/dL, ΔLDL-C = -27.9 ± 1.3 mg/dL, n = 18) and a poor response group (reduction < 20 mg/dL, ΔLDL-C = -3.7 ± 2.5 mg/dL, n = 26), baseline levels of campesterol and sitosterol were higher in the good response group. CONCLUSION Ezetimibe monotherapy reduced LDL-C and increased HDL-C, with the reduction of LDL-C being greater in patients with higher levels of cholesterol absorption markers.