"I want to affirm there have been many cases of total global amnesia
that have come to my attention." Dr. Beatrice Golomb, PI, NIH funded
Statin Study.

Even if cognitive confusion proves rare...it could affect "swarms of
cases," with dire consequences in certain professions, such as
commercial-airline pilots, according to {Duane} Graveline, a former
U.S. Air Force and Army flight surgeon.

~~~~~~~~~~~~~~~~~~~

Side effects of statins under more scrutiny

Memory lapses and disorientation are among risks

BY SUSAN JENKS
FLORIDA TODAY

Ever since experiencing two bouts of severe amnesia on the
cholesterol-lowering drug Lipitor, retired physician Dr. Duane
Graveline has struggled to make this possible memory risk better known.
Duane Graveline, retired dcotor who trained as an astronaut, is the
author of Lipitor: Thief of Memory. Image by Rik Jesse, FLORIDA TODAY

The part"-time Merritt Island resident and former astronaut may get
help early next year, with the anticipated publication of a large
federally funded study assessing cognitive effects -- good and bad --
of Lipitor and other statins, as these multibillion-dollar, top-selling
heart drugs are called.

Dr. Beatrice Golomb, the scientist heading the University of
California, San Diego, study, said she could not reveal specifics of
her 1,000-patient study before publication.

But, she said, "I want to affirm there have been many cases of total
global amnesia that have come to my attention," including Graveline's
case.

Golomb and Graveline support the use of statin drugs where patients
have a high-risk for heart attacks and stroke. In a recent article for
Geriatric Times, Golomb described the benefits to those with
coronary-artery disease "as incontrovertible," while Graveline said in
a recent interview, "for a high-risk person, we need to call on all the
help we can."

However, each contends, subtle side effects that have been missed in
pharmaceutical-company-sponsored studies may emerge in greater numbers,
as more and more Americans go on these drugs.

Even if cognitive confusion proves rare, as Lipitor's maker Pfizer
contends, it could affect "swarms of cases," with dire consequences in
certain professions, such as commercial-airline pilots, according to
Graveline, a former U.S. Air Force and Army flight surgeon.

Millions of individuals in the United States already take
cholesterol-lowering drugs, which work by blocking a liver enzyme the
body needs to make cholesterol, a pearly white substance in the blood
that is a key ingredient in cell membranes and plays a vital role in a
number of bodily functions.

At last count, statins racked up $15.2 billion a year in sales and led
the market share for prescription drugs, according to IMS Health, which
collects marketing data for the pharmaceutical industry.

'Lonely orator'

Graveline said he first began taking Lipitor to lower his cholesterol
several years ago on the advice of physicians at Johnson Space Center
in Houston, where he went for his annual physical. Although his
cholesterol was "moderately high," at the time, he said, otherwise, he
was healthy and in good shape.

But six weeks after starting the drug, his wife found him aimlessly
wandering around in their back yard after his morning walk, unable to
recognize her or his surroundings.

"The first time it happens, you worry about common things," said
Graveline, referring to what may have caused his memory loss. "The
doctor in me suspected the drug, but my colleagues said I was wrong --
'Lipitor doesn't do that.' "

When it happened a second time, about a year later, he said, it
convinced him of the connection.

"It became me against everybody else when I decided to take myself off
the drug," Graveline said.

His experience turned him into a self-described "lonely orator," until
he discovered the statin study, run by Golomb in California, and other
case reports of memory lapses, confusion and disorientation began to
pour in, he said.

In July 2003, Duke University researchers published a review article of
60 patients with statin-associated memory problems in the journal
Phamacotherapy.

"In my judgment, the evidence that statins play a causal role is
overwhelming," Graveline said.

That conviction has led him to pen his personal experiences in
"Lipitor, Thief of Memory: Statins and the Misguided War on
Cholesterol," published early this year; do countless interviews across
the country; and even run a Web site (www.spacedoc.net), where others
can share concerns about statins and learn more about them.

"No, I don't want statins taken off the market, but I do want their
true side effects made available to doctors and to the public," he
insisted. "I want doctors to know if a patient's memory is screwed up,
to think of statins first -- not to say, as they do most of the time,
'Oh, you're over age 50, so you need to expect this type of memory
loss.' "

Graveline said Lipitor and other statins interfere with cholesterol
production, not only in the liver, but also -- in some patients -- in
the brain, where cholesterol plays a vital role in nerve-cell
communication.

Extensively studied

Pfizer's Dr. Barbara LePetri dismisses the idea.

LePetri, senior medical director for the drug company and head of its
Lipitor program, said Lipitor does not cross the blood-brain barrier,
as Graveline suggests, adding "not all statins are the same."

Also, since it was first marketed in 1997, she said, Lipitor has been
tested in more than 400 clinical trials and more than 80,000 patients
worldwide, with the most common side effects gas, constipation and mild
abdominal cramping.

"Lipitor is the most extensively studied statin drug out there," she
said, stressing the drug's overall safety profile.

And, referring to an early study, where investigators reported seven
amnesia cases in 2,502 patients, she said, "It's important to note that
patients on placebo (sugar pills) often report the same side effects as
we see on the drug."

When a statin drug interferes with cholesterol production, the liver
makes up the loss by taking cholesterol from the bloodstream. That
reduces the amount circulating in the blood, lowering an individual's
overall cholesterol number, as well as that of low-density
lipoproteins, the so-called "bad cholesterol."

At present, six statins are in the marketplace.

The newest, Crestor, already has come under attack by Public Citizen's
Health Research Group, the Washington, D.C.-based consumer-advocacy
group, which runs an online subscription site called Worst Pills, Best
Pills news at www.worstpills.org.

The group has petitioned the U.S. Food and Drug Administration to take
Crestor off the market, citing "unique kidney toxicity" and several
early cases in pre-market testing of rhabdomyolysis, a potentially
fatal disorder reviewed in a recent Journal of the American Medical
Association article that causes a breakdown of muscle tissue.

"We knew about Crestor and its problems long before it went on the
market," said the Health Research Group's director, Dr. Sidney Wolfe,
who predicted it eventually would be withdrawn. "But there are
unnecessary delays with this drug."

Crestor officials referred to a recent statement by the Food and Drug
Administration, in which the agency said Crestor's "safety profile is
in line with other statins" and has been misrepresented in the press.

As to possible memory problems associated with statins, Wolfe took a
cautionary view.

Although, he indicated, he has heard a number of consumer complaints
about neurologic difficulties, "the true risk cannot be evaluated,"
until Golomb's study results are available, Wolfe said.

Risks and benefits

That statins come without a risk-free guarantee surprises few doctors
who frequently prescribe these agents to patients in hopes of
protecting them from heart disease, the nation's No. 1 killer, or
stroke, the third leading cause of death.

"Like any other drugs, there are risks and there are benefits -- be it
an over-the-counter drug or a prescription medication," stressed Lake
County cardiologist Dr. Ken Kronhaus, who often acts as a spokesman for
the American Heart Association.

"Each of these pills carry a tiny bit of poison inside and, hopefully,
a lot of benefit," he said. But, in general, with statins, "as the risk
factors for heart disease go up, so do the benefits."

Kronhaus said "what's key here is picking the population you treat
carefully" and evaluating patients on a case-by-case basis, according
to individual risk.

Dr. Chris Finton, vice president of medical affairs and executive
director of Health First Heart Institute at Holmes Regional Medical
Center, agreed.

Finton said the medical community is still in its infancy, regarding
"our knowledge of atherosclerosis" -- the process by which the arteries
harden and raise the risk for heart attacks and stroke.

That includes the role of cholesterol, which, Graveline now argues,
plays a lesser role in heart-disease risk than inflammation in the
artery walls.

"I put far more stock in this (inflammation) if you are defining
heart-disease risk," Graveline said. "Just because cholesterol is
associated with atherosclerotic plaque doesn't mean it causes it."

But Finton remains unconvinced.

"Sure, there are some patients with high cholesterol who never have a
heart attack," which reflects the complexity and "multitude of factors"
involved in plaque formation, he said.

"We are just beginning to identify which patients benefit most or who
won't benefit on statin drugs," he said. "We're not there yet."

In the meantime, Finton cautioned patients against abruptly stopping a
statin drug without talking to a physician first.

"If you think you are having a side effect, talk to your doctor," he
said.

Contact Jenks at 242-3657 or sjenks@flatoday.net