Future outlook: changing perspectives on best practice

The guidelines recently released by the National Cholesterol Education Program call for more aggressive lowering of the level of low-density lipoprotein (LDL) cholesterol and a significant increase in the number of patients eligible for therapy that lowers the level of LDL. Despite the efficacy of statins in lowering the LDL level and in reducing the risk of a coronary event or stroke, other cholesterol-lowering therapies are needed. Some patients are unable to tolerate statins or are not candidates for statin therapy because of liver enzyme abnormalities, age, a preference for nonsystemic therapy, or a modestly elevated LDL level. For those patients, bile acid sequestrants, intestinal bile acid transport inhibitors, acyl coenzyme A:cholesterol acyltransferase inhibitors, and a number of nonselective cholesterol absorption inhibitors are alternative treatments. However, those agents vary in their effectiveness in reducing the level of LDL. Their use often does not reduce the LDL level to the extent desired or is compromised by patients' poor compliance with therapy because of inconvenient dosing or unpleasant side effects. Ezetimibe, the first selective inhibitor of intestinal cholesterol absorption, is a promising alternative to the agents listed above. When ezetimibe is used either as monotherapy or in combination with a statin, once-daily dosing reduces the level of LDL by an average of 18%.