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 points.
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 or higher.
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 LDL levels.
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; E-mail:
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)
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