Update to the NCEP ATP III guidelines recommends aggressively treating LDL cholesterol levels in high-risk patients

July 12, 2004

Bethesda, MD - With the publication of numerous statin-therapy trials since the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (NCEP) published its evidence-based guidelines for cholesterol management in 2001, the NCEP has updated the recommendations and calls for more intensive cholesterol treatment, especially in patients at high risk for CHD[1].

The message from the updated report is that lower is in fact better for high-risk patients, with the NCEP expert panel calling for LDL cholesterol treatment targets <100 mg/dL in patients at high risk for CHD. The recommendations go even further, however, with the panel recommending that in very high-risk patients, aggressively lowering LDL cholesterol to <70 mg/dL is now a therapeutic option for clinicians.

The updated ATP III NCEP guidelines are published in the July 12, 2004 issue of Circulation and are endorsed by the National Heart, Lung, and Blood Institute, the American College of Cardiology, and the American Heart Association.

Aggressive LDL lowering in high-risk patients

Since the publication of ATP III, five major clinical trials with statin therapy and clinical end points have been published. According to the NCEP panel, these trials addressed issues not adequately covered in previous statin trials and have important implications for the management of patients with lipid disorders, especially high-risk patients.

The five trials include the Heart Protection Study (HPS), the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) study, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack TrialLipid-Lowering Trial (ALLHAT-LLT), Anglo-Scandinavian Cardiac Outcomes TrialLipid-Lowering Arm (ASCOT-LLA), and the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) trial.

We believe it is important to give clinicians the therapeutic option to go very low in these high-risk patients.

"It has been shown before that there is great benefit in going from high to low cholesterol in high-risk patients," Dr Scott Grundy (University of Texas Southwestern Medical Center, Dallas) told heartwire . "What hadn't been resolved before is whether or not there was some additional benefit in going from low to very low. The Heart Protection Study and PROVE-IT both addressed this question, and the answer is yes, there is additional benefit in getting cholesterol levels below 70 mg/dL. We believe it is important to give clinicians the therapeutic option to go very low in these high-risk patients."

ATP III LDL cholesterol cutoffs for lifestyle interventions and drug therapy in different risk categories

Risk category

LDL cholesterol goal

Initiate therapeutic lifestyle changes

Consider drug therapy

High risk: CHD or CHD risk equivalents (10-year risk >20%)

<100 mg/dL (with an optional goal of <70 mg/dL) >100 mg/dL >100 mg/dL (consider drug options if LDL-C <100 mg/dL)

Moderately high risk: two or more risk factors (10-year risk 10%-20%)

<130 mg/dL (with an optional goal of <100 mg/dL) >130 mg/dL >130 mg/dL (consider drug options if LDL-C 100-129 mg/dL)

Moderate risk: two or more risk factors (10-year risk <10%)

<130 mg/dL >130 mg/dL >160 mg/dL

Low risk: <1 risk factor

<160 mg/dL >160 mg/dL >190 mg/dL (consider drug options if LDL-C 160-189 mg/dL)

The recommendations contained in the guidelines state that for high-risk patientsthose with established CHD or cerebrovascular disease, diabetes or those with two or more cardiovascular risk factors (>20% risk of CHD within 10 years)the overall goal remains LDL cholesterol levels <100 mg/dL. In the very high-risk subsetthose with established CHD who also have multiple risk factors, including diabetes, metabolic syndrome, or severe or poorly controlled risk factorsthe guidelines offer a new therapeutic option of aggressively treating LDL levels to <70 mg/dL. Even in very high-risk patients with LDL levels <100 mg/dL, the new guidelines support using drug therapy to bring LDL cholesterol down to <70 mg/dL.

Overall, in high-risk patients, the update calls for drug therapy in those with LDL cholesterol levels between 100 and 129 mg/dL. In contrast, the ATP III guidelines set the threshold for drug therapy for high-risk patients at LDL cholesterol >130 mg/dL. Drug treatment was previously optional in those patients with LDL levels between 100 and 129 mg/dL.

In moderate-risk patientsthose with two or more risk factors for CHD (10% to 20% risk of CHD within 10 years), the NCEP targets remain LDL cholesterol <130 mg/dL but give clinicians a therapeutic option to treat to <100 mg/dL. To reach this goal, drug therapy is an option to get the LDL levels below 100 mg/dL, said Grundy.

"Previous studies such as ASCOT have shown a benefit in getting LDL cholesterol to less than 130 mg/dL. In that trial, patients with LDLs less than 130 mg/dL had a significant lowering of cardiovascular risk when they were treated with statin therapy," Grundy said. "Doctors now have the option to bring the LDL down further, below 100 mg/dL in these moderate-risk patients."

The panel recommends that when LDL-lowering therapy is employed, the intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL cholesterol levels. The NCEP report also states that although the potential benefit of HDL-raising therapy has evoked considerable interest, "current documentation of risk reduction through controlled clinical trials is not sufficient to warrant setting a specific goal value for raising HDL-C."

"The major message from the recommendations is that getting the LDL cholesterol down is very important in high-risk patients," said Grundy. "However, we need to go another step further and get it very low, especially in those high-risk patients who would benefit from aggressive lipid-lowering therapies."

Diabetes as a risk factor strengthened

In addition, Grundy tells heartwire that the new guidelines have been "strengthened" for diabetic patients. The 2004 recommendations support the inclusion of patients with diabetes in the high-risk category. In patients with diabetes plus CVD, the panel notes that it is reasonable to attempt to achieve very low LDL levels (<70 mg/dL).

In diabetic patients without CVD, the data support the recommendation of lowering LDL to <100 mg/dL, although whether to start lipid-lowering therapy when the baseline LDL levels are already below 100 mg/dL remains left to clinical judgment, he said. Similarly, if a patient with diabetes is considered to be low riskyoung age, lack of other risk factorsthen the decision to initiate drug therapy when LDL is <130 mg/dL is left to clinical judgment. However, in both these type of patients, lifestyle modifications are clearly recommended, he said.

Like ATP III, the update emphasizes cholesterol lowering in those 65 years or older. High-risk elderly persons are included in the recommendations for intensive LDL-lowering treatment.



Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.