Cholesterol Guidelines: The Strength of the Science Base
and the Integrity of the Development Process|
Statement from Barbara Alving, M.D., Acting Director,
National Heart, Lung, and Blood Institute
A letter initiated by the Center for Science in the Public
Interest (CSPI) calls on the National Cholesterol Education
to form an independent panel to review the Adult Treatment Panel
III (ATP III, 2001) recommendations for cholesterol management
and a 2004 update to these recommendations. The September
signed by CSPI Executive Director Michael Jacobson, PhD, and
34 physicians and researchers, questions the scientific basis
and objectivity of
these clinical practice guidelines. The National Institutes of
Health and the National Heart, Lung, and Blood Institute
coordinates the NCEP, are preparing a detailed response to the
letter. The ATP III recommendations and the update are based
on a careful
analysis of strong and abundant scientific evidence. The guidelines
are objective and the process by which they were developed has
Since its creation in 1985, the NCEP has sought to educate
health professionals and the public about high blood cholesterol
risk factor for coronary heart disease (CHD) and the benefits
cholesterol in the prevention of CHD. The NCEP is a partnership.
At its core is the Coordinating Committee, composed of representatives
of over 35 partner organizations including major medical and
health professional associations, voluntary health organizations,
programs, and governmental agencies. The NCEP, under the sponsorship
of the Coordinating Committee, has developed a series of science-based
clinical guidelines on cholesterol management, known as Adult
Treatment Panel reports. These reports are drafted by a panel
experts and undergo thorough review by the Coordinating Committee
and other recognized scientific authorities outside NIH.
ATP III, like the two previous guideline reports from the NCEP,
was based on an extensive examination of the scientific evidence
panel of leading scientific experts. This report has been well
received and widely implemented by the medical community. In
July of 2004,
the NCEP issued an update to ATP III, based on an analysis of
5 new clinical trials of cholesterol lowering with statin drugs.
was drafted by a working group selected for their expertise from
the members of the original ATP III, and an expert representative
of the American Heart Association (AHA) and of the American College
of Cardiology (ACC). The update paper was reviewed by the NCEP
Coordinating Committee and by the scientific and steering committees
of AHA and
ACC, and was endorsed by NHLBI, AHA, and ACC.
The update offered therapeutic options for the physician’s
consideration rather than firm recommendations for the most part.
This was done in recognition of the fact that there are a number
of ongoing clinical trials that will address the benefits of
lowering LDL cholesterol well below currently recommended goal
The CSPI–initiated letter specifically calls into question
the ATP III clinical recommendations for cholesterol lowering in
moderately high risk women and the elderly who do not have heart
disease. NHLBI affirms the scientific rationale for these recommendations.
Using all available clinical trial and epidemiological evidence is
a well-founded and widely accepted approach to the development of
clinical practice guidelines. NCEP applies this approach to all recommendations
to lower cholesterol – both lifestyle changes and medication – as
well as to all populations, including women and the elderly.
There is abundant clinical trial and epidemiological evidence
showing that lowering LDL cholesterol (by statins or other means)
heart attacks in men with or without prior coronary heart disease.
In addition, there is considerable evidence from trials of patients
with coronary heart disease or other high risk conditions that
statins benefit women and men, older and younger patients, and
and without diabetes. Since narrowing of the coronary arteries
is a lifelong gradual process, there is no scientific basis to
that cholesterol lowering suddenly becomes beneficial the moment
a person has a heart attack. It is far more consistent with the
entire body of scientific evidence to hold that cholesterol lowering
also beneficial in people without heart disease, but becomes
even more critical after a heart attack, when the person’s
risk for a future heart attack rises significantly.
Recent clinical trials, including the Heart Protection Study,
strengthen ATP III recommendations for older persons, an age
group which exhibits
the highest risk for heart attacks. Regarding research on women,
this same large trial included over 5,000 high-risk women and
showed the same benefit of LDL-lowering therapy as observed in
this trial, over 1,800 women had diabetes and they too benefited
LDL lowering. Although clinical trials have not included large
numbers of moderately high risk women (without heart disease),
studies show that these women are just as likely to develop cardiovascular
disease as men. ATP III thus applied the same guidelines to both
men and women at moderately high risk.
It is imperative that we apply what we have learned from research
in order to prevent or delay the development of heart disease,
the leading killer of women and men. For tens of thousands of
Americans, including women and the elderly, the first sign of
is sudden death. Sound public health policy demands that the
significant risk for illness and death in women and the elderly
with science-based prevention recommendations.
The letter also questions the ATP III recommendation that high-risk
patients with diabetes should be considered for cholesterol-lowering
drug therapy. In fact, there is conclusive clinical trial evidence
that cholesterol-lowering drug therapy significantly reduces
cardiovascular risk for patients with diabetes, both those with
and without existing
heart disease. This finding has been amply documented by a major
primary prevention trial in patients with diabetes that was published
after the ATP III update. Once a person with diabetes develops
cardiovascular disease, the mortality rate is very high, so the
objective in diabetes
treatment is to prevent the development of cardiovascular disease
in the first place. Clinical trials show that cholesterol lowering
contributes significantly to attaining this objective.
The letter questions the objectivity of ATP III and the update,
stating that the recommendations “may not be scientifically justified” since
panel members have had interactions with the pharmaceutical industry.
We have noted before that the experts who are most knowledgeable
in a subject area are also the same people whose advice is sought
by industry, and most guideline panels include experts who interact
with industry. To ensure that the guidelines are objective and
science-based, NHLBI employs a rigorous development and review
process. Expert panel
members are carefully selected for their scientific and medical
expertise and their integrity, multiple levels of reviewers scrutinize
drafts of the guidelines from a variety of scientific perspectives,
and financial disclosure is published by the peer-reviewed journal.
Many journals and organizations are currently reexamining their
approaches to managing disclosure of financial interests. NHLBI
further policy in this area to refine the process for management
of potential conflict of interest.
In summary, the ATP III guidelines and update were developed
using a thorough evidence-based process that has high integrity.
guidelines are derived from an objective analysis of the
evidence and NHLBI stands behind them. There are several
clinical trials in high-risk individuals currently underway. The
of these trials will help determine whether revisions to
the current recommendations are scientifically warranted. At that
will consider establishing another panel.
More detailed information on the issues raised by the letter
and the NHLBI response to the letter will be made available
response to the letter has been finalized.
The ATP III guidelines
and update can be found online (at:
NHLBI is part of the National Institutes of Health (NIH),
the Federal Government's primary agency for biomedical
NIH is a component of the U.S. Department of Health
and Human Services. NHLBI press releases and fact sheets
can be found
online at the NHLBI Web site (at www.nhlbi.nih.gov).