The intestinal absorption of biliary and dietary cholesterol as a drug target for lowering the plasma cholesterol level

Elevated plasma low-density lipoprotein cholesterol levels constitute a major risk factor for coronary heart disease. The plasma low-density lipoprotein cholesterol concentration is dictated partly by the efficiency of intestinal cholesterol absorption. The efficacy of treatments designed to block cholesterol absorption is partially offset to the extent that the liver compensates for the interruption to the enterohepatic movement of cholesterol by increasing the rate at which it synthesizes cholesterol. Currently, the most widely-used treatment for hypercholesterolemia is based on a class of agents (statins) that partially inhibit cholesterol synthesis within the body. Recent clinical trials with a unique, potent, and selective cholesterol absorption inhibitor (ezetimibe) used in combination with lower doses of various statins showed an additive reduction in plasma low-density lipoprotein cholesterol levels which equaled the reduction achieved with maximal doses of statins given alone. Combination therapy using a statin and this novel cholesterol absorption inhibitor represents an efficacious new approach to the treatment of hypercholesterolemia in the general population.