National Cholesterol Education Program (NCEP) Guidelines: An Overview of ATP III and Subsequent Modifications

The management of elevated cholesterol centers around evidence-based guidelines. The Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III [ATP III]) was published in December 2002.

Since the ATP III guidelines were released, five major clinical trials of statin therapy with clinical end points have been published. In response to these trials, the NCEP issued interim guidelines as an addendum to the ATP III guidelines regarding the management of cholesterol.

Key Aspects of ATP III

The ATP III guidelines address issues related to the detection, evaluation, and treatment of cholesterol disorders. The ATP III algorithm starts with determining lipoprotein levels after a 9-12 hour fast. While total cholesterol correlates with cardiovascular risk, the level of LDL-C determines the overall risk of adverse cardiovascular events. Higher HDL-C levels are protective against cardiovascular events.

Following lipid profile determination, patients are classified on the basis of risk factors. Patients who are determined to be high risk have coronary heart disease (CHD) or CHD risk equivalents. CHD risk equivalents are risk factors that pose a risk just as high as CHD. These include noncoronary forms of cardiovascular disease (CVD), such as symptomatic carotid artery disease, peripheral vascular disease, abdominal aortic aneurysm. Lipid levels, medical history, and risk factors allow the classification of patients into different risk categories that are useful in determining the treatment strategy.

Treatment Approaches

Treatment consists of behavioral and pharmacological approaches. The behavioral approach is known as therapeutic lifestyle changes (TLC) and involves exercise, weight management, and diet modification. Of these drugs, statins cause the largest reductions in LDL-C and triglycerides and a significant elevation in HDL-C. Because of their dramatic effects and tolerable side effect profile, statins have become the focal point of cholesterol management, with the addition of the other drug categories as deemed necessary.

Modifications to ATP III Guidelines

The results of recent clinical trials led the NCEP to issue modifications to the ATP III guidelines in July 2004. These modifications suggest that, for some patients, more intensive lowering of LDL-C is beneficial for reducing cardiovascular event risk.

According to the authors, these new statin trials provide new information on the benefits of LDL-lowering medications for people in risk categories that ATP III could not make definitive recommendations for when the original guidelines were issued. They add that, in general, evidence from these trials reinforces the recommendations from ATP III, especially those concerning the benefit of LDL-lowering medications for patients with diabetes or those who are elderly.

The modifications suggest that, for some patients, more intensive lowering of LDL-C is beneficial for reducing cardiovascular event risk. The revised guidelines offer alternative therapeutic goals of LDL-C < 70 in high risk patients and LDL-C < 100 in moderately high risk patients.

Impact on High-Risk Patients

The recommendations for modifications to the ATP III treatment algorithm impact patients with high risk the most. While the LDL treatment goal is still LDL-C < 100 mg/dL, HPS and PROVE IT support an optional treatment goal of LDL-C < 70 mg/dL in high risk patients, especially diabetics, even when the baseline or on-treatment LDL-C is already < 100 mg/dL. Adding nicotinic acid or fibrates to statin therapy can also help reach the therapeutic goal.

Impact on Moderately High-Risk Patients

For patients with moderately high risk, the LDL treatment goal is still LDL-C < 130 mg/dL. For patients with baseline or on-TLC levels of 100-129 mg/dL, initiation of an LDL-lowering drug is an appropriate therapeutic option to achieve a goal of LDL-C < 100 mg/dL.

Read also: Eligibility for National Awards

Key Clinical Trials Influencing the Guidelines

Several clinical trials have played a crucial role in shaping the NCEP's recommendations and the subsequent modifications to the ATP III guidelines.

Heart Protection Study (HPS)

Patients with LDL-C ≥ 130 mg/dL benefited most from LDL-C reductions. In diabetic patients with CVD, statin administration to achieve an LDL-C goal < 70 mg/dL is reasonable, regardless of baseline LDL-C.

PROSPER Study

The PROSPER study demonstrated decreased composite endpoint, major coronary events, and CHD mortality as a result of LDL-lowering therapy in older patients with or without established CHD.

ALLHAT-LLT

Unlike others, this study did not demonstrate a decreased risk in hypertensive patients. This could have been due, however, to the large crossover of higher-risk subjects to the lipid-lowering treatment arm, the unblinded nature of the study, and the difference in cholesterol between patients on pravastatin and those receiving usual care.

ASCOT-ALL

This study supported the therapeutic option of administering LDL-lowering therapy to reach a goal LDL-C < 100 mg/dL in patients at moderately high risk with an LDL-C 100-129 mg/dL.

PROVE IT

This study tested the effects of intensive LDL-C lowering beyond standard targets on the incidence of major coronary events. High levels of atorvastatin caused an even greater reduction in composite endpoint, which was correlated with a 35 percent lower LDL-C level in patients treated with high levels of atorvastatin. This study lent support to the HPS study, suggesting an optional therapeutic threshold for LDL-C < 70 mg/dL in high risk patients.

Therapeutic Lifestyle Changes (TLC)

The guidelines recommend the initiation of TLC in (a) high-risk patients with LDL-C ≤ 100 mg/dL, (b) moderately high or moderate-risk patients with LDL-C ≤ 130 mg/dL, or (c) low risk patients with LDL-C ≤ 160 mg/dL. Therapeutic lifestyle changes remain an essential modality in clinical management.

Combination Therapy

If a high-risk person has high triglyceride levels or a low high-density lipoprotein (HDL) cholesterol level, consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug.

LDL Cholesterol Goals

For moderately high-risk persons (two or more risk factors and 10-year risk of 10 to 20 percent), the recommended LDL cholesterol goal is less than 130 mg per dL (3.35 mmol per L); an LDL cholesterol goal of less than 100 mg per dL is a therapeutic option on the basis of available clinical trial evidence. The studies demonstrate benefits of lowering LDL-C by 30 to 40 percent, even in patients whose baseline LDL-C is 100-129 mg/dL.

tags: #national #cholesterol #education #program #guidelines