Dual inhibition, newer paradigms for cholesterol lowering

Coronary heart disease (CHD) is the leading cause of death in United States. The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III recommends new lower cholesterol levels, particularly for patients at moderate and high risk for coronary disease. Low-density lipoprotein (LDL) cholesterol is primarily the target of hypolipidemic drugs. The NCEP ATP III recommends an LDL cholesterol goal of <100 mg/dL in high-risk patients and an LDL cholesterol goal of <70 mg/dL as a therapeutic option, especially in patients with very high risk of CHD. Statins are potent LDL cholesterol-lowering drugs, but they are not as effective as fibrates and niacin in improving levels of triglycerides or high-density lipoprotein cholesterol. Ezetimibe represents a new class of hypolipidemic drugs that inhibit cholesterol absorption in the small intestine. The combination of ezetimibe with statins has been more effective than monotherapy alone in many randomized trials. LDL cholesterol reduction with statin occurs mainly with the initial dose, with relatively smaller reductions seen at higher doses. Ezetimibe was also shown to be useful in various population subgroups such as African-Americans, men and women, elderly and aged, and also those with kidney disease. We review various randomized clinical trials that used ezetimibe along with other hypolipidemic drugs like statins and fibrates. We also discuss the adverse effects of the various lipid-lowering drugs and their important drug interactions.