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 over-priced. 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 L.D.L., 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. Ronald 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 three 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, John Carey, who did a superb
job of explaining the medical research, the truth is that medical
researchers have been questioning the theory that widespread use of
statins to lower cholesterol will save lives for many years.
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 the Other Drug Wars,” 1999).
Occasionally, doubts popped up in the mainstream press and then disappeared.
Five years ago, veteran healthcare blogger Matthew Holt pointed to a BMJ article suggesting that stains 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. John 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 sub-groups 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 LA Times,
from 2001 to 2003 Dr Bryan 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
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. World-wide sales
totaled $33 billion in 2007. More than 18 million American now take
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 5 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 Annals 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 5 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 of 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
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 at 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 Alzheimer’s 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 30–day supply. In 2006, the drug brought in $1.5
billion with sales climbing 25% 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 January 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
When I return to the saga of the “Cholesterol Con,” in the second
installment of this post, I am going take a closer look at the American
Heart Association—and others who stood to gain by persuading Americans
of the absolute link between high levels of cholesterol and heart
It is a story that begins long before Pfizer and other drug makers
invented statins. And it explains why so few American doctors stood up
and questioned the widespread use of drugs like Lipitor.
The belief that cholesterol causes heart disease wasn’t just a theory.
It became a matter of faith, brought to us by a motley group that
included food companies advertising margarine and corn oil, the
American Heart Association, and doctors who joined the bandwagon. At
first the American Medical Association resisted—but soon it too
capitulated. Finally, when the American College of Cardiology signed
on, it became very difficult for physicians to speak out.
At that point, anyone who questioned the cholesterol connection could
easily be painted as “reckless”—a doctor willing to put thousands of
lives at risk by encouraging patients to question what had become the
Holy Grail of cardiac care.