New LDL cholesterol guidelines raise questions

Experts Set Lower Low for Levels of Cholesterol" was front page news last month. In all but one newspaper, reporters neglected to mention that virtually all the experts in question had ties to pharmaceutical companies that make cholesterol-lowering drugs. Financial disclosures were not revealed on the Web site of the National Cholesterol Education Program, which was the source of the new treatment guidelines.

Only a local newspaper, Newsday, reported the fact that most of the physicians who set the new recommendations had a conflict of interest. Within a few days, each physician's financial disclosure information appeared on the relevant Web sites. Virtually all had received money, most often in the form of honoraria or grants, from at least ten different drug companies.

The new guidelines immediately made an estimated eight million Americans--whose cholesterol levels had been normal just the day before--candidates for drug therapy. The "safe" level of LDL cholesterol, the type that increases the likelihood of getting heart disease, used to be 130. Now, people at risk for heart disease are told to get their LDL levels lower than 100, and those at the highest risk are encouraged to get their levels below 70. Most people cannot get their cholesterol that low with diet and exercise, so long-term drug therapy is the usual prescription. And statins are the drug class of choice (Lipitor, Zocor, Pravachol, Mevacor, Lescol, Crestor).

"The evidence is quite strong, but it is just short of being definitive," explained Dr. James Cleeman, coordinator of the National Cholesterol Education Program (NCEP), referring to five studies that published results since 2001. That's when the same committee of experts last issued cholesterol treatment guidelines. The NCEP has been extremely influential in promoting the idea that high cholesterol is an important risk factor that should be treated--even when there is no sign of heart disease. The NCEP takes no pharmaceutical industry funding, and Dr. Cleeman is the only member of the guidelines committee without a financial conflict of interest.

The NCEP is a division of the National Heart, Lung and Blood Institute, the federal agency charged with "reducing illness and death from heart disease by reducing the percentage of Americans with high blood cholesterol." Its Web site (www.nhlbi.nih.gov/chd) features a large headline: "Live Healthier, Live Longer." Much time and money have gone into clinical trials trying to prove that lowering cholesterol with diet and/or drugs will prolong life--even for people without heart disease. All that has been proven so far, is this: Statin drugs prolong life for some men with cardiovascular disease and high cholesterol.

The NCEP does not recommend different guidelines for women. It should. Last May, the Journal of the American Medical Association (JAMA) published a scientific review of 13 clinical trials that evaluated the effects of cholesterol-lowering medications on women.

In the six trials that involved women without heart disease, the reviewers, Drs. Judith M.D. Walsh and Michael Pignone, found that drug-treated women did not live longer than untreated women. As for the other reason healthy women might take cholesterol-lowering drugs--to reduce their odds of having a heart attack--the "current evidence is insufficient to determine this conclusively," according to Walsh and Pignone. Last year, another government agency called the Agency for Healthcare Research and Quality (AHRQ) attempted to clarify the effectiveness of cholesterol drugs in women and came to exactly the same dead end.

Yet you won't learn any of this from the information disseminated by the NCEP. Nor will you learn that heart disease may be the leading cause of death in women, but nearly 80% of the deaths occur after age 75. In fact, that's why the trials are inconclusive for women without heart disease. The trials lasted only about four years and most of the women who participated were in their sixties. Too few had heart attacks in the four-year period. Good news for women, bad news for drug companies. Heart disease researchers are not doing much to clarify things for women; only 20% of all studies reviewed by the AHRQ provided separate findings on women.

In women with heart disease, statins have been shown to provide a modest reduction in the rate of non-fatal heart attacks and revascularization procedures (coronary bypass surgery or angioplasty). Middle-aged men who have heart disease or who are at very high risk for developing heart disease are the most likely to benefit from statins. If they do not have heart disease, statins will modestly reduce their odds of having a non-fatal heart attack. However, they too have reason to be concerned about the lack of complete information on statins' risks.

NCEP's new treatment guidelines describe statin drugs as "remarkably safe," but they fail to mention some significant holes in the evidence provided by the major clinical trials. Not all of them have published the number of people who die from causes unrelated to heart disease. This is extremely important information because the few trials that did provide data relating to deaths from other causes produced disturbing findings that have not been widely reported. For example, the trials involving women with heart disease found that statins reduced cardiovascular mortality but that benefit was canceled, inexplicably, by a higher rate of deaths from other causes. Some researchers suspect that there might be some other harm associated with the statin drugs.