Cholesterol absorption inhibitors for the treatment of hypercholesterolaemia

• Published in: Drugs (New York, N.Y.) N.Y.), 2002, Vol.62 (16), p.2333-2347
• Main Authors: SUDHOP, Thomas, VON BERGMANN, Klaus
• Format: Article
• Language: English
• Subjects: Anticholesteremic Agents - therapeutic use; Azetidines - therapeutic use; Biological and medical sciences; Cholesterol - metabolism; Clinical Trials as Topic; Drug Synergism; Ezetimibe; General and cellular metabolism. Vitamins; Humans; Hypercholesterolemia - drug therapy; Medical sciences; Pharmacology. Drug treatments; Phytosterols - therapeutic use; Sterol O-Acyltransferase - antagonists & inhibitors; Sterol O-Acyltransferase 2; Structure-Activity Relationship
• ISSN: 0012-6667; 1179-1950
• DOI: 10.2165/00003495-200262160-00002

The benefits of lipid lowering therapy on coronary heart disease have been clearly established in many clinical trials on primary and secondary prevention. Despite the availability of potent lipid lowering drugs, many patients do not reach the current treatment goals. This paper reviews new therapeutic approaches in lipid lowering drugs focusing on compounds which lower cholesterol absorption. The role of plant sterols and stanols, new acyl-CoA:cholesterol O-acyl transferase (ACAT) inhibitors, microsomal triglyceride transfer protein (MTP) inhibitors, and ezetimibe are summarised. Although the lipid lowering effect of plant sterols and plant stanols is only moderate, their use as functional foods is beneficial for patients with mild hypercholesterolaemia and is able to enhance the lipid lowering effect of HMG-CoA reductase inhibitors (statins). The role of ACAT inhibitors that might also inhibit cholesterol absorption remains unclear. Avasimibe, the first oral bioavailable ACAT inhibitor, has entered phase III trials. However, the presently available data in humans do not indicate a clear clinical benefit. The role of MTP inhibitors, which exhibit remarkable effects on all plasma lipids, also remains unclear, as safety concerns must first be addressed. Ezetimibe, the first available 2-azetidinone, succeeded in phase III trials showing remarkable effects in inhibition of cholesterol absorption as well as cholesterol lowering. The synergistic effect of co-administration of ezetimibe with statins seemingly offers a new approach in reaching the therapeutic goals.