Many
doctors have come to believe that the cholesterol-lowering
drugs called statins (Lipitor, Zocor, Pravachol, Mevacor,
Crestor) are safer than low-dose daily aspirin. That becomes
apparent whenever statins are featured in the media as
a wonder drug for the prevention of heart disease. In
fact, there's a growing consensus among cardiologists
that all adults should take a statin whether or not they
are at high risk.
Yet
women have been underrepresented in the major clinical
trials in which people with and without heart disease
were randomly assigned to take a statin or a placebo (dummy
pill) every day for several years. Women made up less
than one-third of all the study participants. Put that
together with the fact that women under the age of 75
years have a low rate of heart attack and stroke. Add
this disturbing bit of news from University of British
Columbia researchers who conducted a thorough review of
the five prevention clinical trials: only two of the five
trials released their data regarding the serious adverse
effects* suffered by the study participants who were taking
statins. Working with what they had, that is, the data
from only two of the statin trials, the researchers found
that statins did not prolong life for men or women. Worse,
the benefit of taking statins (a reduced rate of non-fatal
heart attacks and stroke) was offset by an increase in
the serious adverse events. Until all the statin trials
release their serious adverse effects data, the public
will not know whether these drugs are safer than low-dose
aspirin.
The
sparse information that people receive about cholesterol
treatment was unintentionally but aptly illustrated recently
by one of the country's top medical journals. The Journal
of the American Medical Association, or JAMA, regularly
publishes a "patient page," which amounts to
a layman's translation of one of the more important papers
published in each issue.
The
May 12, 2004 issue of JAMA contained a review of all trials
in which women with high cholesterol had been randomly
assigned to take a drug or a placebo. (Most of the trials
involved a statin.) Judith M.E. Walsh, MD, MPH, and Michael
Pignone , MD, MPH conducted the review. Their conclusion:
For women without heart disease, drugs did not prolong
life or reduce the odds of dying of heart disease. The
drug may reduce non-fatal cardiac events (heart attack,
stroke, etc.), but "current evidence is insufficient
to determine this conclusively." For women with heart
disease, drugs do not affect mortality but will reduce
non-fatal events.
Turn
to the patient page in the same issue of JAMA, and none
of this important information can be found. Instead, six
sentences are devoted to statins explaining how they work;
the need for regular lab tests to check for statin-induced
liver damage; the possibility of muscle damage, etc. The
reader will find nothing about the drugs' effectiveness
(or ineffectiveness) in preventing or treating heart disease.
The rest of the page was given over to the usual information
about exercise and smoking cessation. Worse, it has outdated
information about the importance of a low-fat diet; despite
the fact that a review of all relevant studies found that
it has little effect on heart disease prevention (see
below). The patient page is intended for physicians to
photocopy and give to their patients.
And
what about the unreported serious adverse effects of statin
drugs? Not a mention in the patient page, of course, but
there it was in the "comments" section of the
JAMA article. At the end of their review, Drs. Walsh and
Pignone discuss possible explanations for why statins
do not prolong life for women with heart disease. The
drugs reduce the odds of dying of heart disease, but that
benefit is canceled by a higher rate of death from other
causes.
"Possible
explanations include chance, the limitation that not all
studies reported both heart disease and total mortality...
Another potential explanation might be an increase in
a competing cause of mortality, for example, an increase
in hemorrhagic stroke with cholesterol-lowering therapy.
However, information on the causes of non-heart disease
mortality is not available for all the trials, so this
possibility cannot be proven. [emphasis added] Publication
of cause-specific mortality for many of the larger trials
could help to clarify the association between cholesterol-lowering
therapy and total mortality."
There
you have it, the full story is not yet available on the
safety of cholesterol-lowering drugs, though these trials
were published years ago. Traditionally, researchers design
trials to answer specific questions. In this case: Does
this drug reduce the rate of heart attacks and strokes
or the rate of cardiovascular death? But the drug itself
might cause deaths from other causes, and as Drs. Walsh
and Pignone wrote, not all studies reported deaths from
other causes. These concerns are relevant to men, as well.
As
for the doctors who say that statins are safer than aspirin,
they might one day be proven correct. But it took more
than 100 years to get the full story on aspirin. (In fact,
there might be more to learn.) Gastrointestinal bleeding
and rarely, hemorrhagic stroke are both potentially fatal
side effects of chronic use of aspirin, even at low doses.
And the dangers of giving aspirin to children who have
flu or chicken pox have only been known to be associated
with the rare risk of Reye's syndrome for less than 30
years.
For
More Information:
-
Go to the Web site, sponsored by the above-mentioned University
of British Columbia researchers (www.ti.ubc.ca). In the
archives, locate Therapeutics Letter No. 48 "Do statins
have a role in primary prevention?
-
Go to the archives of the British Medical Journal at www.bmj.com
for the review of all studies assessing the heart disease
prevention benefit of reduced dietary fat intake. Find
the March 31, 2001 issue featuring "Dietary fat intake
and prevention of cardiovascular disease: systematic review"
by Lee Hooper et al.
--
*Serious
adverse effects are any untoward medical occurrences that
result in death, are life threatening, require hospitalization
or prolongation of hospitalization, or results in persistent
or significant liability.
Maryann
Napoli, Center for Medical Consumers (C) June 2004
