"The enzyme these drugs block is critical for lots of activities in the
body," says Dr. James M. Wright, professor of medicine at the
University of British Columbia. "So to think that it is going to be all
for the good is very naïve."

http://www.businessweek.com/magazine/content/04_47/b3909127_mz018.htm

Business Week online

NOVEMBER 22, 2004

SCIENCE & TECHNOLOGY

Wondering about a wonder drug
Statins cut cholesterol but long term cognitive and muscle effects are
a mystery

"...while the benefits of statins are well established, some doctors
argue that their side effects have not received adequate scrutiny. A
subset of patients reports muscle pain, but it's unclear how widespread
these symptoms may be or if they could be a sign of long-term muscle
injury. In addition, some scientists are concerned that the drugs could
be having a negative impact on cognitive function in certain patients.
If that's the case, is the effect permanent? And who is most at risk?
The pharmaceutical industry has spent millions of dollars promoting the
merits of statins and searching for new uses. Much less energy has been
directed at answering the nagging questions

--------snip-------

Nonetheless, troubling uncertainties remain. Take the issue of muscle
pains. In clinical trials they seemed to be rare. But physicians such
as Dr. James K. Liao, director of vascular medicine research at Brigham
& Women's Hospital in Boston and a big supporter of statins, believes
muscle pains are much more common, occurring in 15% to 20% of his
patients. Doctors often rely on a blood test for an enzyme called
creatine kinase CK to determine if patients are suffering from
statin-related muscle pain. If the CK level is elevated, physicians may
change the statin dose or try a different drug. If it's normal, some
doctors may assume the muscle pains are not caused by the drug and
won't alter the medication.

---------snip-------

Problem is, some research shows patients can have normal CK levels and
still suffer muscle damage. In addition, in 2002, Dr. Helmut Sinzinger,
a professor in the Nuclear Medicine Dept. at the University of Vienna,
published a paper showing that in 111 patients taking a variety of
statins who did not have elevated enzyme levels or suffer any muscle
pain, almost 10% did show a rise in a marker in the blood for possible
muscle injury. He says that means some patients could be suffering
subtle and undetected muscle injury. One theory: Statins may deplete an
antioxidant called coenzyme Q10, used by mitochondria, the cells'
energy factories. Merck says it did animal studies on this issue and
found no link between COQ10 levels and muscle disorders.

--------snip--------

In a seeming paradox, though, statins may also have negative effects on
the brain. Dr. Matthew F. Muldoon, associate professor of medicine at
University of Pittsburgh School of Medicine, published a study in 2000
looking at the effect of Merck's statin Mevacor on cognitive function.
He compared the performance of 209 patients before getting any
medication and six months after taking either Mevacor or a sugar pill.
The results: Statin users did worse on tests of attention and
psychomotor speed. Muldoon says this may be a temporary impact that
dissipates as the body adjusts to the drug. But it's also possible that
statin users suffer longer-term negative cognitive impact

--------snip--------

Dr. Beatrice A. Golomb, a researcher at University of California at San
Diego, hopes to answer some of those questions. Funded by the National
Institutes of Health, she is leading a study looking at the effects of
statins on the central nervous system. The 1,000-patient trial will
study patients receiving Merck's Zocor, Bristol-Myers Squibb's (BMY )
Pravachol, or a placebo for six months and measure any positive or
negative changes in cognition, irritability, aggression, and serotonin
levels. Golomb says she has been in touch with many patients and
families reporting problems with statins ranging from memory lapses to
changes in personality.

--------snip--------

Without more studies, though, manufacturers will have a hard time
putting the concerns to rest. "The enzyme these drugs block is critical
for lots of activities in the body," says Dr. James M. Wright,
professor of medicine at the University of British Columbia. "So to
think that it is going to be all for the good is very naïve." Given
the swelling ranks of people taking statins, drugmakers would be wise
to investigate their risks as closely as they do their benefits."