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Cholesterol Guidelines: Strength of the Science Base and the Integrity of the Development Process

For Immediate Release:
September 24, 2004

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 Program (NCEP) 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 23 letter, 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 (NHLBI), which 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 high integrity.

Since its creation in 1985, the NCEP has sought to educate health professionals and the public about high blood cholesterol as a risk factor for coronary heart disease (CHD) and the benefits of lowering 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, community 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 of scientific 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 by a 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. The update 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 levels.

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) prevents 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 those with and without diabetes. Since narrowing of the coronary arteries is a lifelong gradual process, there is no scientific basis to believe 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 is 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 men. In this trial, over 1,800 women had diabetes and they too benefited from LDL lowering. Although clinical trials have not included large numbers of moderately high risk women (without heart disease), epidemiological 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 heart disease is sudden death. Sound public health policy demands that the significant risk for illness and death in women and the elderly be addressed 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 the 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 is developing 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. The guidelines are derived from an objective analysis of the substantial scientific evidence and NHLBI stands behind them. There are several clinical trials in high-risk individuals currently underway. The results of these trials will help determine whether revisions to the current recommendations are scientifically warranted. At that time, NCEP 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 after the response to the letter has been finalized.

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