Cholesterol absorption inhibitors: Defining new options in lipid management

Abstract

Although many studies have documented that reduction of plasma cholesterol levels decreases the risk of coronary artery disease, it remains the most common cause of death in the Western world. Current therapeutic options are effective in lowering cholesterol, especially in clinical trials, but clinical application is not optimized for many reasons. Dietary restriction for long‐term management of hypercholesterolemia is helpful but usually insufficient to reduce low‐density lipoprotein cholesterol (LDL‐C) to goal levels. Powerful drugs are available, but these are often insufficient to meet the clinical demands for cholesterol‐lowering therapy. Phytosterols and phytostanols have been partially effective by providing some inhibition of absorption of cholesterol. Compounds that specifically and more effectively block intestinal absorption of dietary and biliary cholesterol should provide a significant new agent for altering lipoprotein concentrations favorably. Ezetimibe is the first of this class of compounds that act at the gut epithelium to reduce cholesterol absorption in the milligram dose range markedly. Clinical studies indicate that ezetimibe effectively decreases LDL‐C by 15 to 20% as monotherapy, with a favorable safety profile. Moreover, results from preliminary clinical trials indicate that ezetimibe given concomitantly with a statin provides additive efficacy. The combination represents a new approach to lipid management, achieving greater LDL‐C and triglyceride reductions and greater improvements in HDL‐C than statin monotherapy. This could offer another important option in clinical practice for management of hypercholesterolemic patients.