Cholesterol absorption inhibitors as a therapeutic option for hypercholesterolaemia.
The development of cholesterol-lowering drugs (including a variety of statins, bile acid-binding resins and recently discovered inhibitors of cholesterol absorption) has expanded the options for cardiovascular prevention. Recent treatment guidelines emphasise that individuals at substantial risk for atherosclerotic coronary heart disease should meet defined targets for LDL cholesterol concentrations. Combination therapy with drugs that have different or complementary mechanisms of action is often needed to achieve lipid goals. Existing approaches to the treatment of hypercholesterolaemia are still ineffective in halting the progression of coronary artery disease in some patients despite combination therapies. Other patients are resistant to conventional drug treatment and remain at high risk for the development and progression of atherosclerotic cardiovascular disease and alternative approaches are needed. The discovery and development of ezetimibe (a novel, selective and potent cholesterol absorption inhibitor) has advanced the treatment of hypercholesterolaemia. New agents including the phytostanol preparation FM-VP4 and inhibitors of acyl coenzyme A:cholesterol acyltransferase, the apical Na(+)-dependent bile acid transporter and microsomal triglyceride transfer protein may also play a future role in combination therapy. This review focuses on the recent progress in the molecular mechanisms of intestinal cholesterol absorption and transport, and novel therapeutic approaches to inhibit the cholesterol absorption process.
Burnett
John R
JR
Royal Perth Hospital, Department of Core Clinical Pathology & Biochemistry, PathWest Laboratory Medicine WA, Wellington Street Campus, GPO Box X2213, Perth, WA 6847, Australia. john.burnett@health.wa.gov.au
Huff
Murray W
MW
D000102:Acetyl-CoA C-Acyltransferase / Q000037:antagonists & inhibitors; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D050197:Atherosclerosis / Q000517:prevention & control; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D002791:Cholesterol, Dietary / Q000378:metabolism*; D015507:Drugs, Investigational / Q000494:pharmacology* / Q000627:therapeutic use; D000069438:Ezetimibe; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy*; D007408:Intestinal Absorption; D010840:Phytosterols / Q000494:pharmacology / Q000627:therapeutic use
D000924:Anticholesteremic Agents; D001384:Azetidines; D001647:Bile Acids and Salts; D002352:Carrier Proteins; D002791:Cholesterol, Dietary; D015507:Drugs, Investigational; C445524:FM-VP4 compound; D010840:Phytosterols; C106092:microsomal triglyceride transfer protein; D000102:Acetyl-CoA C-Acyltransferase; D000069438:Ezetimibe