Pharmacological strategies for lowering LDL cholesterol: statins and beyond

A continuous, graded relationship exists between LDL cholesterol (LDL-C) levels and risk of cardiovascular disease (CVD). This finding has been confirmed at progressively lower levels of LDL-C by results from clinical trials of therapies, particularly high-potency statins, which provide increasingly greater reductions in LDL-C levels. On the basis of this clinical trial evidence, progressively lower LDL-C goals for increasing numbers of patients, stratified by absolute CVD risk, have been recommended in guidelines for cholesterol management and CVD prevention. Some notable exceptions have been made, however, such as patients with end-stage renal disease or heart failure. To achieve low LDL-C goals, statins are first-line pharmacological therapy and can be combined with other agents to provide additional reductions in LDL-C levels as well as improvements in other lipoprotein fractions. Investigational agents that reduce LDL-C levels by other mechanisms are under development and could provide additional therapeutic strategies to achieve optimal LDL-C levels. These agents could be particularly appropriate for patients with severely elevated LDL-C levels, such as those with genetic dyslipidemia, for whom maximal drug therapy is insufficient to reduce LDL-C concentrations to recommended levels.