State of the art in cholesterol management: targeting multiple pathways.

The relationship between increased serum levels of total cholesterol and increased risk of coronary heart disease (CHD) is widely accepted, as is the corollary that lowering elevated levels of low-density lipoprotein (LDL) cholesterol, a significant risk factor, reduces CHD mortality. Although statins are the most widely used agents to lower LDL cholesterol levels and demonstrate significant clinical benefits, alternate and/or additional treatment strategies are also being studied. One such approach for which several classes of agents are available is the nonspecific inhibition of intestinal cholesterol and bile acid absorption. Although all of these inhibitors-which include bile acid sequestrants, cholesterol absorption blockers, and plant stanols-reduce cholesterol concentrations within liver cells and increase the expression of LDL receptors, they are limited in their effectiveness because of poor tolerability and compensatory effects by the liver that blunt their ability to lower LDL. Ideally, the combination of a statin and another agent that specifically targets cholesterol absorption and promotes excretion while simultaneously decreasing synthesis may provide the greatest therapeutic benefit. The recent development of selective cholesterol inhibitors, including ezetimibe, provides an approach to lowering LDL that has significant potential both as monotherapy and in combination therapy.