Update on Cholesterol Guidelines: More-Intensive Treatment Options for Higher Risk Patients|
National Heart, Lung, and Blood Institute, American College of Cardiology, and American Heart Association Endorse Report
A 2004 update to the National Cholesterol Education Program's (NCEP)
clinical practice guidelines on cholesterol management advises physicians
to consider new, more intensive treatment options for people at
high and moderately high risk for a heart attack. These options
include setting lower treatment goals for LDL ("bad")
cholesterol and initiating cholesterol-lowering drug therapy at
lower LDL thresholds.
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:
*High and Very High Risk: For high-risk patients, the overall goal
remains an LDL level of less than 100 mg/dL. But for people at very
high risk, a group that is considered a "sub-set" of the
high-risk category, the update offers a new therapeutic option of
treating to under 70 mg/dL. For very high-risk patients whose LDL
levels are already below 100 mg/dL, there is also an option to use
drug therapy to reach the less than 70 mg/dL goal.
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: For moderately high-risk patients, the
goal remains an LDL under 130 mg/dL, but the update provides a therapeutic
option to set a lower LDL goal of under 100 mg/dL and to use drug
therapy at LDL levels of 100 - 129 mg/dL to reach this lower goal.
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.
*Lower/Moderate Risk: The update did not revise recommendations
for lower risk persons: those with moderate risk (2 or more risk
factors plus an under 10 percent risk of a heart attack in 10 years)
or those with 0 to 1 risk factor.
According to the report, the absolute benefits for people at the
lower levels of risk are less clear cut and the recent clinical
trials do not suggest a modification of treatment goals and cut
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:
ATP III: The goal for high-risk patients is an LDL of <100 mg/dL.
Update: LDL<100 mg/dL is still an overall goal for high-risk
patients; for very high-risk patients, a therapeutic option is to
treat to <70 mg/dL.
ATP III: The threshold for cholesterol-lowering drug treatment
for high-risk patients was 130 mg/dL or higher, and cholesterol-lowering
drugs for LDL 100 - 129 mg/dL were "optional."
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.
ATP III: For moderately high-risk persons, the LDL treatment goal
is <130 mg/dL and drug therapy is recommended if LDL is 130 mg/dL
Update: A therapeutic option is to set the treatment goal at LDL
<100 mg/dL, and to use drug therapy if LDL is 100 - 129 mg/dL
to reach the goal.
ATP III: Achieving a certain percentage lowering of LDL cholesterol
was not emphasized.
Update: When LDL-lowering drug therapy is used in high- and moderately
high-risk patients, it is advised that the intensity of therapy
be sufficient to achieve at least a 30 to 40 percent reduction in
ATP III: Initiate therapeutic lifestyle changes (TLC) in patients
whose LDL cholesterol numbers are above goal levels.
Update: In addition to patients with LDL above goal, any person
at high- or moderately high-risk who has lifestyle-related risk
factors is a candidate for TLC regardless of LDL level.
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;
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).