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Am Fam Physician. 2004;70(8):1591-1592

A more recent Practice Guideline on this topic is available.

The complete version of 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 and provided evidence-based recommendations on the management of high blood cholesterol levels and related disorders. Since then, five major clinical trials of statin therapy with clinical end points have been published. In response to these trials, the NCEP recently issued interim guidelines as an addendum to the ATP III guidelines regarding the management of cholesterol. The addendum was published in the July 13, 2004, issue of Circulation and is available online at The fully revised guidelines will be released in June 2005.

The five clinical trials that the authors reviewed include the Heart Protection Study (HPS), the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial–Lipid-Lowering Trial (ALLHAT-LLT), Anglo-Scandinavian Cardiac Outcomes Trial–Lipid-Lowering Arm (ASCOT-LLA), and the Pravastatin or Atorvastatin Evaluation and Infection–Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial.

According to the authors, these new statin trials provide new information on the benefits of low-density lipoprotein (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 new trials also offer new information on the efficacy of risk reduction in high-risk persons with relatively low LDL cholesterol levels.


Based on evidence from the recent clinical trials, the authors made the following recommendations for modifications in the treatment algorithm for LDL cholesterol:

• Therapeutic lifestyle changes remain an essential modality in clinical management. Therapeutic lifestyle changes have the potential to reduce cardiovascular risk through several mechanisms beyond LDL lowering.

• In high-risk persons, the recommended LDL cholesterol level goal is less than 100 mg per dL (2.60 mmol per L).

• In high-risk persons, an LDL cholesterol level goal of less than 70 mg per dL (1.80 mmol per L) is a therapeutic option on the basis of available clinical trial evidence, especially for patients at very high risk.

• In high-risk persons, if the LDL cholesterol level is at least 100 mg per dL, use of an LDL-lowering medication is indicated simultaneously with lifestyle changes.

• In high-risk persons, if the baseline LDL cholesterol level is less than 100 mg per dL, institution of an LDL-lowering drug to achieve an LDL cholesterol level of less than 70 mg per dL is a therapeutic option on the basis of available clinical trial evidence.

• 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. When triglyceride levels are at least 200 mg per dL (2.25 mmol per L), non-HDL cholesterol level is a secondary target of therapy, with a goal of 30 mg per dL (0.80 mmol per L) higher than the identified LDL cholesterol goal level.

• 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. When the LDL cholesterol level is 100 to 129 mg per dL (3.35 mmol per L), at baseline or on lifestyle therapy, initiation of an LDL-lowering drug to achieve an LDL cholesterol level of less than 100 mg per dL is a therapeutic option on the basis of available clinical trial evidence.

• Any person at high risk or moderately high risk who has lifestyle-related factors (such as obesity, physical inactivity, low HDL cholesterol level, elevated triglyceride level, or metabolic syndrome) is a candidate for therapeutic lifestyle changes to modify these risk factors regardless of LDL cholesterol level.

• When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30 to 40 percent reduction in LDL cholesterol levels.

• For people in lower risk categories, recent clinical trials do not modify the goals and cut points of therapy.

Coverage of guidelines from other organizations does not imply endorsement by AFP or the AAFP.

This series is coordinated by Michael J. Arnold, MD, Assistant Medical Editor.

A collection of Practice Guidelines published in AFP is available at

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Copyright © 2004 by the American Academy of Family Physicians.

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