The Cholesterol Con -- Where Were the Doctors?

[Guest guest]

The Cholesterol Con -- Where Were the Doctors?

By Maggie Mahar, Health Beat.

For years, medical studies have challenged the efficacy of

cholesterol-lowering drugs. Why are we just hearing about this now?

After the stock market bubble burst, the New York Times asked: " Where

were the analysts? Why didn't they warn us? "

To be perfectly honest, this was a somewhat disingenuous question. As

experienced financial journalists understood all too well, the

analysts plugging the high-flying issues of the 1990s were employed

by Wall Street firms raking in billions as investors bet their nest

eggs on one hot stock after another. It really wasn't in their

employers' interest for analysts to tell us that their products were

wildly overpriced. When a small investor wades into the financial

world, there are two words he needs to keep in mind: caveat emptor.

But physicians, I firmly believe, are different from the folks

employed by Merrill Lynch. (I don't mean to knock people who work at

ML. I am simply saying that they have a very different job

description.) When consulting with your doctor, you should not have

to be wary. You are not a customer; you are a patient. And your

physician is a professional who has pledged to put your interests

ahead of his or her own.

This brings me to the question I ask in my headline: During the many

years of the Cholesterol Con, where were the doctors? When everyone

from the makers of Mazola Corn Oil to the Popes of Cardiology assured

us that virtually anyone could ward off heart disease by lowering

their cholesterol, why didn't more of our doctors raise an eyebrow

and warn us: " Actually, that's not what the research shows " ?

No doubt, you've heard about the recent Business Week cover

story, " Do Cholesterol Drugs Do Any Good? " , which blew the lid off

the theory that " statins " -- drugs like Lipitor, Crestor, Mevacor,

Zocor and Pravachol -- can cut the odds that you will die of a heart

attack by slowing the production of cholesterol in your body and

increasing the liver's ability to remove LDL, or " bad cholesterol, "

from your blood.

It's true that these drugs can help some people -- but not nearly as

many as we have been told. Moreover, and this is the kicker, we don't

have any clear evidence that they work by lowering cholesterol.

Although medical research suggests that statins can definitely

benefit one group -- men under 70 who already have had a heart

attack -- researchers are no longer convinced that the drugs stave

off a second attack by lowering the patient's cholesterol. The drugs

do lower cholesterol, but that is not what helps the patient.

In other words, researchers are questioning the bedrock assumption

that high levels of " bad cholesterol " cause heart disease. " Higher

LDL levels do help set the stage for heart disease by contributing to

the buildup of plaque in arteries. But something else has to happen

before people get heart disease, " Dr. M. Krauss, director of

atherosclerosis research at the Oakland Research Institute, told

Business Week. " When you look at patients with heart disease, their

cholesterol levels are not that [much] higher than those without

heart disease, " he added. " Compare countries, for example. Spaniards

have LDL levels similar to Americans', but less than half the rate of

heart disease. The Swiss have even higher cholesterol levels, but

their rates of heart disease are also lower. Australian aborigines

have low cholesterol but high rates of heart disease. "

" Current evidence supports ignoring LDL cholesterol altogether, " Dr.

Rodney A. Hayward, professor of internal medicine at the University

of Michigan, told Business Week's reporter.

In recent years, researchers have begun to suspect that statins help

patients, not by lowering cholesterol levels, but by reducing

inflammation. If this theory is right, " this seems likely to shunt

cholesterol reduction into a small corner of the overall picture of

heart disease, " the Guardian reported four years ago.

And if the key to statins is that they reduce inflammation, it's

worth keeping in mind that this is what other effective heart

treatments like aspirin and the omega-3 fatty acids found in fish

oils, garlic and vitamin E do -- at a much lower cost and with far

fewer side effects.

But hold onto your hats, I still haven't gotten to what is most

shocking about the cholesterol story. What raises my blood pressure

is the knowledge that Business Week's scoop isn't really " new " news. "

With all due respect to Business Week, which showed real courage in

putting the story on its cover, and to its author, Carey, who

did a superb job of explaining the medical research, the truth is

that medical researchers have been questioning for many years the

theory that widespread use of statins to lower cholesterol will save

lives.

You can find the research questioning the benefits of statins in

medical journals like Lancet (2001) and BMJ (2006), as well as in

reports from medical conferences ( " Tales From the Other Drug Wars, "

1999).

Occasionally, doubts popped up in the mainstream press and then

disappeared.

Five years ago, veteran healthcare blogger Holt pointed to an

BMJ article suggesting that statins might be no better than aspirin.

That same year, Holt raised pointed questions regarding the risk of

taking statins, including possible memory loss. "

Nevertheless, the very next year, the National Cholesterol Education

Program at the U.S. National Heart, Lung and Blood Institute issued

new recommendations that drastically lowered the threshold for statin

therapy. According to its 2004 report, people at a moderately high

risk of developing heart disease (with LDL cholesterol levels between

100 and 129 mg/dL) should be offered statins -- even if they have no

previous history of heart disease. Statin therapy also should be

recommended to very high-risk patients, the panel said, even if their

LDL levels are as low as 70. NCEP declared that the recommendations

applied to both men and women, regardless of age.

The bottom line: NCEP was urging millions of Americans to go on

statins.

Not everyone agreed, recalls Merrill Goozner, editor of " GoozNews, " a

top-drawer investigative healthcare blog. In 2004, a few months after

the new guidelines came out, a coalition of more than 30 academic

physicians and researchers, inspired by Dr. Abramson (author of

Overdosed America: The Broken Promises of American Medicine), decided

to write a letter to the National Heart Lung and Blood Institute

(NHLBI).

Goozner, who does research at the Center for Science in the Public

Interest, organized the group. The letter " outlined all the evidence,

which was there in published clinical trials for anyone who cared to

look, " Goozner recalls, and concluded that while statins " may lower

cholesterol in people at low risk and even many subgroups at moderate

risk of a heart attack ... there was no evidence that the drugs

actually saved lives. "

How could this be, if statins lower the risk of heart attack, at

least for some people? Preventing a heart attack does not necessarily

mean that a life is saved. In many statin studies that show lower

heart attack risk, the same number of patients end up dying, whether

they are taking statins or not. " You may have helped the heart, but

you haven't helped the patient, " says Dr. Beatrice Golomb, an

associate professor of medicine at the University of California, San

Diego, and co-author of a 2004 editorial in the Journal of the

American College of Cardiology questioning the data on statins. " You

still have to look at the impact on the patient overall. "

" The letter we sent to the NHLBI also called for an independent panel

to review the evidence, " Goozner notes, " since the NLHBI panel that

made the recommendations had been dominated by physicians with ties

to statin manufacturers. " Indeed, the National Institutes of Health

later admitted that eight of the nine experts on the panel had

received financing from one or more of the companies that make

statins. (None of the panelists had publicly disclosed their ties to

manufacturers when they made their recommendations.)

Just how much " financing " were the panelists receiving? According to

the Los Angeles Times, from 2001 to 2003 Dr. Brewer, a leader

at the National Institutes of Health, and " part of the team that gave

the nation new cholesterol guidelines in 2004, " had accepted " about

$114,000 in consulting fees from four companies making or developing

the cholesterol-lowering drugs. "

But " this is relative peanuts compared to Dr P. Trey Sunderland III,

a senior psychiatric researcher at the NIH, who took $508,500 in fees

from Pfizer, Inc. whilst collaborating with them and endorsing their

drug [Lipitor], " says Dr. Malcolm Kendrick, who is a member of The

International Network of Cholesterol Skeptics (THINCS) -- a growing

group of scientists, physicians, other academicians and science

writers from various countries.

Dr. Abramson, who is a clinical instructor at Harvard Medical School,

charges that the study that accompanied the updated 2004

guidelines " knowingly misrepresented the results of the clinical

trials that they supposedly relied upon to formulate their

recommendations. The problem is that the experts claimed to rely on

scientific evidence, but they act as if empowered to ignore the

evidence when it is not consistent with their beliefs. "

This is a serious allegation. Keep in mind that statins are the most

popular drugs in the history of human medicine. Worldwide sales

totaled $33 billion in 2007. More than 18 million American now take

them.

Nevertheless, " medical research suggests that only about 40 percent

to 50 percent of that number are likely to benefit, " says

Abramson. " The other 8 or 9 million are exposed to the risks that

come with taking statins -- which can include severe muscle pain,

memory loss, sexual dysfunction -- and one study shows increased risk

of cancer in the elderly -- but there are no studies to show that the

drugs will protect these patients against fatal heart attacks. "

Abramson can cite many studies to support his claims. But first, he

stresses that statins can help some people.

" Statins show a clear benefit for one group, " he says: " People under

65 who have already had a heart attack or have diabetes. But even in

these very high risk people, about 22 have to be treated for five

years for one to benefit. "

What about middle-aged people who are not diabetic and have not had a

heart attack? A 2006 study published in the ls of Internal

Medicine that focused on seven trials involving nearly 43,000 middle-

aged adults concluded that statin use did not cut their chances of

dying from heart disease.

Is there any benefit for this group? " If they are high risk, statins

can be beneficial to people under 65 who haven't had a heart attack,

but 50 such men have to be treated for five years for one to

benefit. " says Abramson. " The other 49 will not be helped. The

problem is that we can't know who is going to be the 50th man, " he

adds. And all 50 will be exposed to the side effects.

Older adults have little to gain. The drugs don't help people over 70

even if they have elevated cholesterol levels, according to a report

in the Journal of American Cardiology.

Finally, " there is no evidence of any benefit for women who don't

already have heart disease or diabetes, " says Abramson. According to

a 2004 article published in the Journal of the American Medical

Association which reviewed all trials in which women with high

cholesterol had been randomly assigned to take a cholesterol-lowering

drug or a placebo, there was no evidence that statins prolonged

women's lives or cut their chances of dying from heart disease.

An editorial published in the Journal of the American College of

Cardiology came to the same conclusion -- though there does seem to

be a risk that women on statins develop memory loss so severe that

their relatives may begin shopping for a nursing home.

Memory loss that can mimic alzheimers is the second most common side

affect for people taking statins, right after muscle pain, according

to researchers at the University of California, San Diego. For a

number of years, they have been running a randomized controlled trial

examining the effects of statins on thinking, mood, behavior, and

quality of life. Separately, the UCSD researchers have been

collecting anecdotal experiences of patients, good and bad, on

statins.

" We have some compelling cases, " Dr. Beatrice Golomb, the study's

lead researcher, told the Wall Street Journal. " In one of them, a San

Diego woman, Jane Brunzie, was so forgetful that her daughter was

investigating alzheimers care for her and refused to let her baby-sit

for her 9-year-old granddaughter. Then the mother stopped taking a

statin. 'Literally, within eight days, I was back to normal -- it was

that dramatic,' said Mrs. Brunzie, 69 years old. "

According to the Journal, " doctors put her on different statins three

more times. 'They'd say, " Here, try these samples. " Doctors don't

want to give up on it,' she said.' Within a few days of starting

another one, I'd start losing my words again,' added Mrs. Brunzie,

who has gone back to volunteering at the local elementary school she

loves and is trying to bring her cholesterol down with dietary

changes instead. "

Returning to Goozner's story, did the letter his group wrote to the

NHLBI in 2004, spark public discussion about the new cholesterol

guidelines? No. " We released the letter to the press, but the

mainstream of the national press ignored us, " Goozner recalls.

In 2008, Goozner is happy to see the statin controversy hit Business

Week's cover -- though he can't help but wonder, " Where were these

guys three years ago? Now, call me a cynic, but why does my perverted

mind think to itself as I watch this coverage: Yeah, now we hear,

just when the world's best-selling drug [Lipitor] is about to go off

patent. "

I suspect Goozer is right. It would have been much harder to publish

this story a few years ago.

But there also was a trigger that probably helped spur the Business

Week investigation. Last month, Merck-Schering/Plough released a long-

awaited study revealing that Vytorin, an expensive combination of two

drugs designed to lower cholesterol, brought no added benefits for

patients suffering from heart disease.

The two cholesterol-lowering drugs were Zocor, which is a statin,

and, Zetia, which is not. When combined, the two drugs did drive

cholesterol levels much lower. But the clinical trial offered no

evidence that the two cholesterol-busters were more effective in

reducing heart attacks than Zocor alone. This raises an obvious

question: is cutting cholesterol levels really the key to avoiding

heart attacks?

The results of the study helped buttress the strong suspicion that

insofar as statins like Zocor do help anyone with heart disease, the

beneficial effect has little to do with lowering cholesterol levels.

Meanwhile, Zocor is now available in a generic form that can be

purchased for less than $6 for a 30-day supply. By contrast, the new

combination, selling under the brand name Vytorin, was fetching more

than $100 for a three-day supply. In 2006, the drug brought in $1.5

billion with sales climbing 25 percent in the first half of 2007 to

over $2 billion, according to IMS Health.

Naturally, Merck and Schering/Plough, who were marketing Vytorin in a

joint venture, were shy about reporting the results of the clinical

trials. It was only when they were threatened with a congressional

investigation that they made the results public on Jan. 15 -- more

than a year and a half after the clinical trials were completed.

The day after the drug makers released the news, the American Heart

Association rushed to their defense, declaring that the study was too

limited to draw conclusions about Vytorin's ability to reduce heart

attacks or deaths compared to Zocor alone. The AHA advised patients

not to abruptly stop taking Vytorin without consulting with the

doctors who had prescribed it.

The New York Times, to its credit, was quick to respond, noting

that " what the [American Heart Association] did not note in its

statement ... was that the group receives nearly $2 million a year

from Merck/Schering-Plough Pharmaceuticals, the joint venture that

markets Vytorin.