It is believed that aspirin is metabolized differently in men and women, resulting in a reduced pharmacological effect in women. Women also are more likely to develop aspirin resistance.

A large analysis has found that in women it is more likely to prevent a stroke, but in men, its main benefit is heart attack prevention.

"It seems to be a solid difference," said Jason Jurva, a cardiologist and assistant professor of medicine at the Medical College of Wisconsin, who was not involved with the study.

The findings, which pulled together results from six so-called primary prevention aspirin trials involving 95,456 men and women, are published Wednesday in the Journal of the American Medical Association.

Primary Prevention Drug for Men

Using aspirin to protect people who haven't had heart attacks, called primary prevention, is an unsettled issue, but it is a standard therapy for preventing second heart attacks.

The six trials took place over the last 17 years and involved doses ranging from 500 milligrams a day to as little as 100 mg every other day. Today, many doctors recommend a daily 81 mg baby aspirin.

The analysis found that as a primary prevention drug in men, aspirin reduced the risk of a heart attack by 32 percent while actually increasing the overall risk of stroke by 13 percent.

However, because men have many more heart attacks than strokes, many doctors prescribe it for primary prevention, especially after men reach age 50.

In women, who have a much higher incidence of stroke than men, the benefit was reversed.

'People Are Puzzled'

It reduced all strokes by 17 percent and cut the risk of the most common type of stroke by 24 percent, but had no effect on reducing heart attacks.

"The real value of our study is to explain to patients what risk they're reducing," said senior author David Brown, chief of cardiology at Stony Brook University Hospital in Stony Brook, NY. "I don't think that before this study there was enough data to confidently say there was a gender-based difference."

Aspirin was associated with only a slight reduction (10 percent) in cardiovascular deaths in women and had virtually no effect on cardiovascular death in men.

It has been known for years that aspirin could reduce the risk of heart attacks in men, but its role in protecting women was unclear, although last year a large trial pointed to its stroke protection.

"I think people are puzzled," said James Stein, an associate professor of cardiovascular medicine at the University of Wisconsin School of Medicine and Public Health in Madison.

Heart disease is the leading killer of women, but they tend to get heart attacks 10 to 15 years later than men, Stein said.

'Personalize It to the Patient'

There are slightly differing recommendations from health organizations for taking aspirin as a primary prevention drug.

Stein said he generally tells all men age 50 and over that they can take one baby aspirin a day.

For women, he recommends waiting until age 60, provided that they have one additional risk factor, such as high blood pressure, smoking or a family history of heart disease.

People with diabetes can take one daily baby aspirin regardless of their age or other risk factors, he said.

"You have to personalize it to the patient," Stein said.

May Be Metabolized Differently in Men and Women

The analysis also found that there were significant risks from aspirin therapy.

Incidents of major bleeding, although less than 0.5 percent overall compared with a placebo, were significantly greater in both men and women on aspirin therapy.

Viewed another way, over the course of 6.4 years aspirin caused one bleeding incident in every 400 women and 300 men.

"Aspirin is not a benign drug," Stein said.

There are a number of theories about why aspirin has a different effect on men and women.

It is believed that aspirin is metabolized differently in men and women, resulting in a reduced pharmacological effect in women. Women also are more likely to develop aspirin resistance.

Also, women have a greater proportion of strokes to heart attacks than men, and men have a greater proportion of heart attacks to strokes. So finding a statistically meaningful benefit is more likely to occur in strokes for women and heart attacks for men.