The update,* published in the July 13 issue of Circulation: Journal of the American Heart Association, is endorsed by the National Heart, Lung, and Blood Institute (NHLBI), the American College of Cardiology, and the American Heart Association. The document is based on a review of 5 major clinical trials of statin therapy** conducted since the 2001 release of the NCEP's cholesterol guidelines known as the Adult Treatment Panel (ATP) III Report. NHLBI, a component of the National Institutes of Health, coordinates the NCEP.
"The recent trials add to the evidence that when it comes to LDL (bad) cholesterol, lower is better for persons with high risk for heart attack," said NHLBI Acting Director Barbara Alving, M.D. "These trials show a direct relationship between lower LDL cholesterol levels and reduced risk for major coronary events. So, it is important to consider more intensive treatment for people at very high risk," she added.
Major recommendations in the update include:
For the overall category of high-risk patients, the update lowers the threshold for drug therapy to an LDL of 100 mg/dL or higher and recommends drug therapy for those high-risk patients whose LDL is 100 to 129 mg/dL. In contrast, ATP III set the threshold for drug therapy for high-risk patients at an LDL of 130 mg/dL or higher, and made drug treatment optional for LDL 100 to 129 mg/dL.
The NCEP defines high-risk patients as those who have coronary heart disease or disease of the blood vessels to the brain or extremities, or diabetes, or multiple (2 or more) risk factors (e.g., smoking, hypertension) that give them a greater than 20 percent chance of having a heart attack within 10 years. Very high-risk patients are those who have cardiovascular disease together with either multiple risk factors (especially diabetes), or severe and poorly controlled risk factors (e.g., continued smoking), or metabolic syndrome (a constellation of risk factors associated with obesity including high triglycerides and low HDL). Patients hospitalized for acute coronary syndromes such as heart attack are also at very high risk.
Moderately high-risk patients are those who have multiple (2 or more) risk factors for coronary heart disease together with a 10 to 20 percent risk of heart attack within 10 years.
For high-risk or moderately high-risk patients, the report advises that the intensity of LDL-lowering drug therapy be sufficient to achieve at least a 30 to 40 percent reduction in LDL levels. This can be accomplished by taking statins or by combining lower doses of statins with other drugs (bile acid resins, nicotinic acid, or ezetimibe) or with food products containing plant stanol/sterols.
The report emphasizes the importance of therapeutic lifestyle changes (TLC --intensive use of nutrition, physical activity, and weight control) for cholesterol management.
"Lifestyle changes continue to be an essential part of controlling cholesterol. TLC has the potential to reduce cardiovascular risk through several mechanisms beyond LDL lowering," said Scott Grundy, M.D., director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center at Dallas and chair of the NCEP working group that developed the update report.
Like ATP III, the update addresses and emphasizes cholesterol lowering in older persons (age 65 or above). High-risk older persons with established cardiovascular disease are included in the recommendations for intensive LDL-lowering therapy.
"Although the update suggests that physicians use their clinical judgment to determine whether intensive LDL-lowering therapy is warranted in older persons, these people should not be excluded from the benefits of LDL-lowering treatment just because of age," said NCEP Coordinator James Cleeman, M.D.
A comparison of the key modifications in the update with the ATP III recommendations follows:
Update: The threshold for cholesterol-lowering drug treatment is lowered to 100 mg/dL or above, and it is recommended that patients with LDL 100 –129 mg/dL receive cholesterol-lowering drug therapy.
According to Dr. Cleeman, the update to the ATP III guidelines is not the final word on LDL goals. There are three ongoing trials in high-risk individuals, which when completed, may lead to a broader recommendation for reaching very low LDL goals in high-risk patients.
To interview Dr. Cleeman, contact the NHLBI Communications Office at 301-496-4236. To interview Dr. Grundy, contact Donna Hansard, University of Texas Southwestern Medical Center at (214) 648-3404; donna.hansard@utsouthwestern.edu .
A copy of the update and information on the ATP III guidelines can be found online at http://www.nhlbi.nih.gov/guidelines/cholesterol/index.htm . A 10-year heart attack risk calculator can be found at http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof .
*Grundy SM, Cleeman JI, Bairey Merz CN, Brewer HB, Clark LT, Hunninghake DB, Pasternak RC, Smith SC, Stone NJ; for the Coordinating Committee of the National Cholesterol Education Program. Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. Circulation. 2004; 110:227-239.
**The five clinical trials reviewed by the NCEP working group were: the Heart Protection Study (HPS), the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial-Lipid Lowering Trial (ALLHAT-LLT), the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA), and the Pravastatin or Atorvastatin Evaluation and Infection-Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22)