New cholesterol guidelines, new treatment challenges

Coronary heart disease (CHD) is the largest single killer of Americans. Epidemiologic trials have indicted low-density lipoprotein cholesterol (LDL) as directly correlating with CHD events, and clinical trials confirmed that lipid-lowering therapy decreases the risk of CHD events. The literature also indicates that only about 18% of these patients are treated to their goal LDL levels. New guidelines from the National Cholesterol Education Program extend the LDL-lowering recommendations, add a new non-high-density lipoprotein cholesterol (non-HDL) goal for patients with hypertriglyceridemia, and increase the number of drug-eligible patients from about 15 to 36 million. Most of those who are eligible for lipid-altering drug therapy have the highest CHD risk and require the most aggressive treatment to achieve goals. This presents a challenge to clinicians: how best to achieve LDL and non-HDL goals. Statins are the most effective agents for lowering LDL and one of the most effective for lowering non-HDL. This efficacy and the ability to reduce CHD risk were well documented in a number of randomized clinical trials. When statin monotherapy fails to achieve goals, a bile acid resin, niacin, or both may be added to lower LDL further, or a fibrate, niacin, or fish oils may be added to lower non-HDL further. Drugs are under development that may enhance our ability to reach LDL and non-HDL goals. Included are a group of so-called super statins, rosuvastatin and pitavastatin; agents that interfere with cholesterol or bile acid transport in the gut, such as ezetimibe; and dual peroxisome proliferator-activated receptor agonists that have both fibrate and thiazolidinedione-like effects.