Managing dyslipidemia in the high-risk patient

Lipid-lowering agents have been shown to reduce morbidity and mortality associated with coronary artery disease (CAD) in all patients. However, these agents are more cost-effective in high-risk patients whose absolute risk of CAD is greater than that of low-risk patients. Furthermore, from preliminary data, it appears that there is greater risk reduction in those subjects achieving lower low-density lipoprotein cholesterol (LDL-C) levels (ie, lower is better). The identification and aggressive treatment of these patients should therefore be a high priority for clinicians. Guidelines from medical organizations, such as the Adult Treatment Panel (ATP) III of the US National Cholesterol Education Program (NCEP), emphasize that patients with CAD, diabetes, or global risk of CAD >20% over 10 years and LDL-C levels >130 mg/dL should receive drug therapy with a goal of reducing LDL-C levels to <100 mg/dL. The recent results of the United Kingdom's Heart Protection Study (HPS) strongly suggest that even those with CAD or who are at high risk and LDL-C levels >100 mg/dL would benefit from drug therapy. Although optimal LDL-C levels have been set at <100 mg/dL for high-risk patients, recent studies show only about 20% of such patients meet these goals. Thus, a large treatment gap remains that needs to be overcome if we are to continue to make significant inroads into preventing further morbidity and mortality in these high-risk subjects. Of therapeutic options available currently and for the near future, statins remain the most effective and well-tolerated form of lipid-lowering therapy. Other therapies include bile acid sequestrants, niacin, and plant stanols. However, none of these is, in general, sufficiently effective as an initial agent to achieve these more aggressive LDL-C goals in the high-risk patient. However, combination therapy with a statin and 1 of these other lipid-lowering agents is useful in patients who are unable to achieve lipid goals on monotherapy. A number of agents for reducing LDL-C levels currently in development may be available in the near future, including 2 new statins: pitavastatin and rosuvastatin. Rosuvastatin, which is in the later stages of the US Food and Drug Administration (FDA) approval process, has been shown to produce significantly greater reductions in LDL-C levels compared with atorvastatin, simvastatin, and pravastatin, and allows more patients to meet lipid goals. Ezetimibe, the first of an entirely new class of LDL-C-lowering agents that inhibit intestinal cholesterol absorption, also appears to offer significant therapeutic value. It is anticipated that these new options will allow clinicians to optimize the management of dyslipidemia in high-risk patients, thereby further reducing the morbidity and mortality of CAD.