Reassessment of National Cholesterol Education Program Adult Treatment Panel-III guidelines: one year later

Abstract

Since the first Adult Treatment Panel (ATP) guidelines from the National Cholesterol Education Program (NCEP), the goals have evolved from national cholesterol awareness and reduction, to the use of increasingly aggressive lipid-lowering strategies in patients at highest risk for coronary heart disease (CHD). The most recent NCEP guidelines from the ATP-III 1 appropriately suggest the most aggressive reduction in low-density lipoprotein (LDL) cholesterol in an expanded group of patients considered to be at highest risk for CHD. Since these guidelines were published approximately 1 year ago, additional clinical trial data suggest that they are already, to a certain extent, out of date. It is now clear that cholesterol reduction may not just need to target certain lipid goals, but also be broadly applied to virtually any individual at high risk for atherosclerotic disease. REDEFINING AN “OPTIMAL” LDL CHOLESTEROL LEVEL The most striking trial data since ATP-III were from the Heart Protection Study (HPS), 2 which assessed the effects of simvastatin 40 mg and/or a combination of antioxidant vitamins versus placebo in a factorial design in 20,536 patients with high risk for CHD. The study population included subjects with history of CHD, other atherosclerotic diseases, and type 2 diabetes mellitus, all consistent with ATP-III “coronary risk equivalent” status. Although the vitamins provided no cardiovascular benefits, simvastatin therapy yielded a 24% mean relative risk reduction in vascular events. Furthermore, this event reduction was maintained whether the baseline LDL cholesterol was above the traditional ATP-III drug cutpoint of 130 mg/dl, in the range for which discretional use of pharmacotherapy is advised (100 to 129 mg/dl), or even below the targeted LDL cholesterol goal of 100 mg/dl. Although the core principle of the NCEP guidelines, the reduction of LDL cholesterol to reduce CHD risk, was validated by HPS, the extent to which this principle should be applied was underestimated by ATP-III. Although LDL cholesterol concentrations 100 mg/dl are considered “optimal” by ATP-III, the findings from HPS suggest high-risk patients benefit from statin therapy even when below this level. Although providing additional guidance for the management of these patients with CHD risk-equivalent status, HPS raises further questions. Has our definition of hyperlipidemia been skewed by the effects of a Westernized diet on lipid levels? Are some nonlipid benefit(s) of statin therapy responsible for the findings of HPS? Do we even need to measure cholesterol in our high-risk patients? Can we grossly simplify the treatment algorithm for high-risk patients by applying an approach similar to HPS? The last question will likely be answered by the Treat to New Targets (TNT) and Incremental Decrease in Endpoints through Aggressive Lipid-lowering (IDEAL) trials, which are currently in progress. These studies will compare the effects of maximal versus conventional doses of simvastatin and atorvastatin in reducing coronary events in large populations. In the interim, it seems prudent to lower LDL cholesterol to 100 mg/dl or by 35% (whichever is greater) utilizing a statin in the setting of CHD risk equivalency.