A new study shows that aspirin therapy for coronary artery disease is
four times more likely to be ineffective in women compared to men with
the same medical history.

Historically, studies have shown that aspirin therapy is less
effective in women than in men, but it has remained unclear how much
less effective and whether this affects patient outcomes, said Michael
Dorsch, clinical pharmacist and adjunct clinical instructor at the
University of Michigan College of Pharmacy.

Dorsch is the lead author of the paper, "Aspirin Resistance in
Patients with Stable Coronary Artery Disease," which is published in
the Annals of Pharmacotherapy.

Originally, Dorsch and his team set out to determine if patients with
a history of heart attacks were more apt to be aspirin resistant than
those with coronary artery disease but no history of heart attack.
They found that gender and not medical history was a predictor for
aspirin resistance, Dorsch said. The results surprised him.

"I was surprised by how big of a difference it was for females," said
Dorsch, who has appointments at the U-M Health System and the U-M
College of Pharmacy, and started the study as a resident at the
University of North Carolina. "This is another piece of information
that affirms we need more studies in women."

Aspirin therapy is a cornerstone in managing heart disease because it
inhibits blood clotting. Aspirin therapy can reduce the risk of a
nonfatal heart attack or stroke by about 23 percent, and an estimated
20 million men and women take a low dose of aspirin (81-325 mg daily)
to control heart disease. But despite its effectiveness, there is
evidence that aspirin is less effective in some patients, and
researchers don't really know why. This can be frightening because
most doctors do not check for aspirin resistance before prescribing
aspirin therapy and therefore presume it's working in the patient when
it may not be, he said.

There isn't enough evidence to show if people who are aspirin
resistant can simply take larger doses, but Dorsch warns that people
taking aspirin on the advice of a doctor shouldn't stop therapy on
account of these results.

Not only did the study quantify how much more effective aspirin
therapy is for men than for women, it is also the first study that
Dorsch knows of to measure aspirin resistance in men and women with
stable coronary artery disease. Previous studies have looked at the
impact of aspirin therapy on people who have had a heart attack.

For the study, researchers randomly selected 100 patients who were
visiting their cardiologist for a regularly scheduled appointment. All
had coronary artery disease but only half had a history of heart
attack. Researchers used a device called VerifyNow Aspirin Assay to
test the percentage of platelet reactivity after blood samples were
exposed to a chemical that causes clotting.

Aspirin works by causing platelet inhibition in the blood, which means
that platelets cannot stick together and this slows the formation of
blood clots that cause a heart attack or stroke.

"This does happen in women, but it doesn't happen in as many women and
it's not as effective," Dorsch said. The testing device uses an
optical sensor to "see" what percentage of the platelets in the blood
sample clump together. Anything less than 40 percent platelet
inhibition is considered aspirin resistant.

"We really don't know the mechanism," Dorsch said. "It could be that
women have a more active platelet system in the body so it's less
likely that platelet action would be inhibited."

In the future, researchers hope to look at aspirin therapy outcomes in
women only and see if those outcomes can be changed. The majority of
testing for aspirin therapy has been on men, so not much is known
about how women respond.

"Heart disease is the number one killer of women in the United States.
Future research should be aimed at finding out the cause of this
increase in aspirin resistance and the effect on outcomes in women
with heart disease." Dorsch said.

The study was funded by the National Institutes of Health.

Abstract:
Aspirin Resistance in Patients with Stable Coronary Artery Disease
with and without a History of Myocardial Infarction

Dorsch et al.

BACKGROUND: Aspirin therapy is a cornerstone in the prevention of
atherothrombotic events, but recurrent vascular events are estimated
to occur in 8-18% of patients taking aspirin for secondary prevention
after 2 years. Estimates of biologic aspirin resistance vary from 5%
to 60%, depending on the assay used. However, the relationship between
biologic measurements of aspirin resistance and adverse clinical
events remains unclear.

OBJECTIVE: To determine whether patients with documented myocardial
infarction (MI) while on aspirin therapy (cases) were more likely to
be aspirin resistant than were patients with coronary artery disease
(CAD) who had no history of MI (controls) and to assess clinical
predictors of aspirin resistance in patients with stable CAD.

METHODS: This case-control study examined aspirin responses using the
VerifyNow Aspirin Assay system in 50 cases and 50 controls who had
taken a dose of aspirin within 48 hours of presentation to the clinic
visit. Odds ratios were estimated to determine the association between
aspirin resistance and MI. Independent predictors of aspirin
resistance were determined using univariate and multivariate analyses.

RESULTS: An increase in the prevalence of aspirin resistance among
cases (16% vs 12% in controls) was not observed (OR 1.40; 95% CI 0.45
to 4.37; p = 0.566). In the overall CAD population, female sex was
independently associated with aspirin resistance (OR 4.01; 95% CI 1.15
to 13.92; p = 0.029).

CONCLUSIONS: Additional large studies are required to understand
whether biologically defined aspirin resistance is associated with
increased risk for cardiovascular events, with special attention paid
to sex differences.

Published Online, 24 April 2007, www.theannals.com, DOI 10.1345/aph.
1H621.

Marilyn