Aspirin not as good for women as for men

Long-term aspirin = reduced risk of dying in women?

Long-term aspirin use associated with reduced risk of dying in women_

Women who take low to moderate doses of aspirin have a reduced risk of death from any cause, and especially heart disease–related deaths, according to a report in the March 26 issue of Archives of Internal Medicine, one of the JAMA/Archives journals.

Some studies have provided evidence that aspirin may reduce the risk of heart disease and some types of cancer, the two leading causes of death in U.S. women, according to background information in the article. However, it is unclear whether aspirin reduces the risk of death overall for women.

Andrew T. Chan, M.D., M.P.H., Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues examined the association between aspirin use and death in 79,439 women enrolled in the Nurses’ Health Study, a large group of female nurses who have been followed since 1976. Beginning in 1980 and again every two years through 2004, the women were asked if they used aspirin regularly and if so, how many tablets they typically took per week. At the beginning of the study, the women had no history of cardiovascular disease or cancer.

A total of 45,305 women did not use aspirin; 29,132 took low to moderate doses (one to 14 standard 325-milligram tablets of aspirin per week); and 5,002 took more than 14 tablets per week. By June 1, 2004, 9,477 of the women had died, 1,991 of heart disease and 4,469 of cancer. Women who reported using aspirin currently had a 25 percent lower risk of death from any cause than women who never used aspirin regularly. The association was stronger for death from cardiovascular disease (women who used aspirin had a 38 percent lower risk) than for death from cancer (women who used aspirin had a 12 percent lower risk).

"Use of aspirin for one to five years was associated with significant reductions in cardiovascular mortality," the authors write. "In contrast, a significant reduction in risk of cancer deaths was not observed until after 10 years of aspirin use. The benefit associated with aspirin was confined to low and moderate doses and was significantly greater in older participants and those with more cardiac risk factors."

There are several mechanisms by which aspirin could reduce the risk of death, the authors note. "Aspirin therapy may influence cardiovascular disease and cancer through its effect on common pathogenic pathways such as inflammation, insulin resistance, oxidative stress [damage to the cells caused by oxygen exposure] and cyclooxygenase (COX) enzyme activity," also linked to inflammation, they write.

Because the study looked at women who made the decision themselves whether or not to take aspirin, as opposed to a clinical trial where women are randomly assigned to aspirin or a placebo, the results do not suggest that all women should take aspirin. "Nevertheless, these data support a need for continued investigation of the use of aspirin for chronic disease prevention," the authors conclude._

These findings differ from the results of other studies regarding the benefits of aspirin use in healthy women, leaving confusion about aspirin’s role, writes John A. Baron, M.D., Dartmouth Medical School, Lebanon, N.H., in an accompanying editorial._

Dr. Baron points out that in the Women’s Health Study, researchers followed almost 40,000 women for 11 years and did not find any reduced risk of cardiovascular or other death associated with aspirin therapy, in contrast to the dramatic risk reduction seen in the Nurses’ Health Study. "Is aspirin really that good or is there some other explanation for the findings that differ so much from those of the WHS and other primary prevention trials?" he writes.

"The difference between the NHS and the aggregated data from the WHS and other trials is too large to be explained by potential weaknesses in the randomized studies," Dr. Baron writes. "At the same time, one has to consider that the observational NHS may not have been able to deal with the differences between aspirin users and non-users."

"Therefore, these new findings by Chan et al cannot overcome the accumulated evidence that aspirin is not particularly effective for the primary prevention of death from cardiovascular disease in women," he concludes.

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 appears online today 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.