Cholesterol absorption inhibition: a strategy for cholesterol-lowering therapy

A clear relationship has been documented between plasma levels of low-density lipoprotein cholesterol (LDL-C) and the risk of coronary heart disease. LDL-C is believed to be key in the pathogenesis of coronary atherosclerosis, although increasing evidence suggests that low levels of high-density lipoprotein cholesterol and elevated triglyceride levels are contributory factors. Chylomicron remnants formed via the exogenous (dietary and biliary) pathway of cholesterol metabolism may also have atherogenic potential. Dietary modification, especially with plant stanol (sterol) ester margarine, which inhibits cholesterol absorption and improves the fatty acid pattern, lowers LDL-C sufficiently in many hypercholesterolaemic patients, and is also a useful adjunct to pharmacological therapy. Cholesterol absorption inhibitors typically lower LDL-C by 10-20%. Ezetimibe, the first selective cholesterol absorption inhibitor, has been shown to lower LDL-C by approximately 18% following a once-daily 10 mg dose, either as monotherapy or as combination therapy. Combination therapy with selective cholesterol absorption inhibitors such as ezetimibe along with statins or fibrates may allow more patients with hypercholesterolaemia to achieve target LDL-C levels compared with treatment with monotherapy. Ezetimibe may be useful in the management of patients who respond poorly to or are unable to tolerate statins, or in patients with hereditary or drug-induced phytosterolaemia.