Aim: Ezetimibe reduces serum low-density lipoprotein cholesterol (LDL-C) levels by inhibiting intestinal cholesterol absorption; however, the effects of ezetimibe, including its pleiotropic effects, have not been fully clarified. The aims of our study were to examine the efficacy of ezetimibe for hypercholesterolemia and its pleiotropic effects.
Methods: Outpatients with hyper LDL-C levels were treated with 10 mg ezetimibe once a day for 12 weeks. Serum lipid profiles, atherosclerotic and inflammatory markers, glucose, insulin, liver function, and cholesterol absorption and synthesis markers were measured before and after treatment.
Results: Seventy-five patients treated with ezetimibe monotherapy and 16 patients treated with combined therapy of ezetimibe with different statins completed this study. Following 12 weeks of ezetimibe monotherapy, serum LDL-C, triglyceride, remnant-like particles cholesterol, matrix metalloproteinase-9, insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, the relative mobility of the peak of the LDL fraction, and cholesterol absorption markers were significantly decreased, and high-density lipoprotein cholesterol and lathosterol were significantly increased. In the combined therapy group, LDL-C and cholesterol absorption markers were significantly decreased after treatment. In patients with a high basal ALT level that were treated with monotherapy, ALT and the AST/ALT ratio were significantly decreased and increased, respectively, after treatment.
Conclusion: Ezetimibe ameliorated not only atherogenic lipid profiles but also atherosclerotic and inflammatory markers, insulin sensitivity, and liver dysfunction in Japanese hypercholesterolemia patients, suggesting that ezetimibe treatment is a beneficial and effective strategy for the treatment of hypercholesterolemia, especially patients with obesity, metabolic syndrome, and/or fatty liver.