Inhibition of synthesis and absorption of cholesterol: A new option in managing hypercholesterolemia

Abstract

Although widely used in lipid lowering therapy, HMG CoA reductase inhibitors or statins (even when administered at high doses) are frequently insufficient to achieve guideline-recommended LDL-C goals for many patients with hypercholesterolemia in everyday clinical practice. Often over half of patients do not achieve LDL-C goal on the initial dose of statin and most of these patients do not reach goal neither after 6 months. Thus, a wide therapeutic gap exists between target LDL-C levels and those typically achieved in clinical practice. A recent and more effective therapeutic strategy, therefore, is to treat the two main sources of cholesterol simultaneously (production of cholesterol, mainly in the liver, and absorption of cholesterol in the intestine) with a complementary mechanism of action, by co-administering ezetimibe, a novel agent inhibiting cholesterol absorption, together with a statin, which inhibits cholesterol production in the liver. Ezetimibe can be effectively co-administered with any dose of any statin and, compared with single inhibition of cholesterol production, afforded by statins alone, provides consistently greater reductions in LDL-C through Dual Inhibition of both cholesterol production and absorption. Here we summarize the pivotal role of both the liver and intestine in the overall balance of cholesterol in the body and describe the clinical impact and relevance of inhibiting both sources of cholesterol either by using ezetimibe/simvastatin as a single tablet or co-administering ezetimibe together with any dose of any statin.