SECOND THOUGHTS ABOUT
ASPIRIN A DAY TO PREVENT HEART ATTACKS
December 2003
A baby aspirin a day keeps a heart attack
away. This widely accepted health
practice was seriously undermined at an
advisory committee meeting of the Food and
Drug Administration (FDA, held in December
2003.) The FDA advisory committee voted
overwhelmingly to reject a petition from the
Bayer Corp. to approve aspirin for reducing
the risk of a first heart attack.
Though an estimated 20
million Americans already take low-dose
aspirin daily to prevent a heart attack,
this is an off-label use—that is, the
aspirin manufacturers have not received FDA
approval for this particular indication. FDA
approval is required, however, once an
aspirin manufacturer plans to advertise the
drug for this use. And once approval is
granted, the drug's packet insert must be
rewritten to inform consumers of the new
indication.
Bayer's petition made the
FDA Cardiovascular and Renal Drugs Advisory
Committee take a critical look at the five
trials (One trial compared aspirin with
vitamin E) in which people without heart
disease took either aspirin or a placebo (a
dummy pill). Altogether there were more than
55,000 participants at anywhere from low to
high risk for a heart attack. Here is what
the cardiologists and other experts on the
committee found in the way of benefit:
Aspirin produced about a 32% reduction in
non-fatal heart attacks. [Translation: An
estimated 3% of all moderate-risk people
will have a heart attack in the next five
years. Daily low-dose aspirin therapy will
reduce their odds to about 2%.] The benefit
is given in terms of a five-year period
because the trials lasted four to seven
years.
Several things troubled
the FDA committee members about the results
of these trials: Aspirin did not have any
mortality reduction benefit; nor did it
reduce the odds of having an ischemic
stroke, which is, arguably, the most feared
consequence of heart disease. Yet aspirin
has the potential for causing another, less
common type of stroke called hemorrhagic
stroke, which is a rupture of a blood vessel
in the brain.
One committee member who
voted to reject Bayer's petition is Steven
Nissen, MD, Medical Director of the
Cleveland Clinic Cardiovascular Coordinating
Center. In a telephone interview, Dr. Nissen
explained, “The data [from the five trials]
were terribly weak.” You always have to
weigh the trade- offs , he said, referring
to hemorrhagic stroke as the major concern.
But the aforementioned 32%
reduction in non-fatal heart attacks applies
to the combined total of all the
study participants, most of whom were men
with differing levels of risk. The committee
hit a snag once it came to individuals. Dr.
Nissen said that he and other committee
members were concerned that daily aspirin,
if taken by people at a low enough risk,
could cause more harm than good. Asked to
define “low enough risk,” he explained that
there was too much uncertainty to answer the
question. “No one in the world can answer
the question of who benefits and who
doesn't, and if there is no answer, then how
could I vote to approve?” he asked.
The fact that women were
underrepresented in the five trials (only
20% of all participants) also troubled Dr.
Nissen. “It may be that the risks exceed the
benefit for women,” he said, “but we simply
don't know—there is not enough data.” Still,
Dr. Nissen was careful to stress that he was
not against aspirin therapy for everyone,
suggesting that people talk over the
decision with their physicians. The FDA
advisory committee “took a lot of heat,”
said Dr. Nissen, referring to its decision
to turn down Bayer's petition and thus
reject the prevailing medical view that
aspirin therapy is good for just about
everyone. “We were called flat earthers ,”
he said.
The FDA is not obligated to
follow the decisions made by its advisory
committees, but the agency usually does. The
committee's decision, though entirely
appropriate, illustrates how the current
system works against consumers who want to
become fully informed before they go on
lifelong drug therapy. Approval would have
meant a rewrite of the drug's packet insert
to include the new indication. And this, in
turn, would have compelled the advisory
committee to identify
the appropriate group of
people for whom the benefit of aspirin
therapy clearly outweighs the
risks. The evidence from the five trials did
not provide the answer; therefore, 20
million people will continue to take daily
aspirin without knowing anything about the
uncertainties of the supporting research.
The advisory committee's
concerns can be contrasted with the practice
guidelines aimed at physicians and published
in 2002 by the U.S. Preventive Services Task
Force. The Task Force concluded that the
number of “cardiac events” prevented by
aspirin therapy far exceeded the number of
hemorrhagic strokes caused by aspirin
therapy. This, too, is based on the combined
results of the same five trials. When the
Task Force tried to break things down for
individuals, it came up with this estimation
for moderate-risk men and women:
“For 1,000 patients with a 3% risk of having
a heart attack in the next five years,
aspirin would prevent eight heart attacks
but would cause one hemorrhagic stroke and
three major gastrointestinal bleeding
events.”
Where it concerns low-risk
people, the Task Force is in agreement with
the FDA advisory committee:
MMMM
“…patients at low risk for coronary heart
disease probably do not benefit from and may
even be harmed by aspirin because the risk
for adverse events may exceed the benefits…”
(Annals of Internal Medicine, 1/15/02).
For More Information:
-Go to www.med-decisions.com
to see one method used by the Task Force to
identify different levels of risk for a
heart attack. The Task Force used an
additional assessment tool based on the risk
information from the Framingham Heart Study,
which has since become outdated.
-The transcript of the
December 8-9, 2003 meeting of the
Cardiovascular and Renal Drugs Advisory
Committee is likely to be posted on the
Internet in February or March. Go to
www.fda.gov and click into “Advisory
Committees.” Then go to this specific
committee and its meeting date.
Maryann Napoli, January 2004 (1)
Danger: Regular Aspirin or Tylenol Can Hurt Your
Kidneys as Evidenced By Professional Athletes
Since Alonzo Mourning, the Miami
Heat's All-Star center, was found to have a kidney
disorder more than a year ago - the same disease
that caused the San Antonio swingman Sean Elliott to
undergo a kidney transplant and eventually forced
him to retire - many players in the National
Basketball Association have grown acutely
concerned about the
use of anti-inflammatory drugs.
Medical experts say that use of
the medication does not cause the kidney disease,
which is called focal segmental sclerosis. But many
doctors say that prolonged use at excessive levels
of anti-inflammatory drugs, from over-the-counter
medicine like ibuprofen and aspirin to prescription
drugs like Vioxx and Indocin, may lead to other
kinds of kidney problems.
By Mike Wise
New York Times
January 29, 2002
Avoid
Long Term Use of Tylenol and Aspirin or Advil