How cholesterol metabolism and transport present novel targets for lipid treatment

The National Cholesterol Education Program treatment guidelines cite reduction of low-density lipoprotein (LDL) cholesterol as the primary therapeutic focus of lipid-modifying treatment. Statin drugs are the most effective agents for reducing LDL. However, the limited efficacy of currently available agents at low doses suggests a need for alternative therapeutic strategies. Serum cholesterol levels reflect a complicated process of synthesis and transport that affords opportunities for intervention at multiple steps in the process. Combination therapy might improve upon lipid-modifying results that can currently be achieved with statin-based therapy, but tolerability issues related to some of the currently available drugs limit their use. Evolving, new classes of lipid-modifying therapies might improve current capabilities to reduce coronary risk. An ideal therapeutic strategy would target cholesterol absorption, excretion, and synthesis. The development of selective cholesterol absorption inhibitors represents a particularly promising approach to enhancement of LDL reduction by means of combination therapy.