A small dose of aspirin taken regularly reduces the risk of heart attack and stroke by about a third in women older than 65 but does not significantly cut the risk in younger women, according to a 10-year study that examined the drug's effects in women for the first time.
For women older than 65, the decision to prescribe aspirin should be made on exactly the same basis as it is in men, the study found.
The findings elevate aspirin's role in preventing heart disease in older women.
"It is clearly beneficial," said Dr. Karol Watson, a cardiologist at UCLA Medical Center, who did not participate in the study.
The unexpected twist is the study's finding that aspirin does not prevent heart attacks or death in women younger than 65, as it does in men, although it reduces the risk of stroke somewhat.
Because aspirin significantly increases the chance of gastrointestinal bleeding, the findings suggest that for younger women, the risk in taking aspirin routinely may outweigh the benefit.
The study is a powerful illustration of the emerging consensus that drugs affect men and women differently.
In previous studies, with few or no women enrolled, researchers found a 32% to 44% reduction in heart attacks and deaths among the young and healthy, starting at about age 45, when they took a small dose of aspirin.
Cardiologists now routinely prescribe a daily baby aspirin for most middle-aged men because of its proven benefit. A baby aspirin contains 81 milligrams, an adult aspirin 325. Some cardiologists do the same for women on the assumption that the effects on the two sexes are similar.
That assumption has now been shown to be faulty.
Heart disease and stroke are the leading killers of men and women in the United States. In 2002, according to the American Heart Assn., men suffered 520,000 heart attacks and women 345,000.
In that same year, men suffered 327,000 strokes and women 373,000.
The new study, conducted by epidemiologist Julie Buring of the Brigham and Women's Hospital in Boston, and her colleagues, enrolled nearly 40,000 healthy women who were at least 45 and had no elevated risk of heart disease.
Half the women were given a 100-milligram aspirin tablet every other day -- slightly stronger than a baby aspirin -- and half were given a placebo. All were monitored for 10 years.
Buring reported Monday at an Orlando, Fla., meeting of the American College of Cardiology that, for those in the study, aspirin reduced heart attacks and death from same by 9% -- not statistically significant. The risk of stroke fell by a statistically significant 17%, and that is important, Buring said, because women suffer more strokes than men.
Over the course of the study, she noted, the subjects had a total of 391 heart attacks and 487 strokes. Statistics from the American Heart Assn., she added, show that women have about 10% more strokes than heart attacks, while men have about 40% fewer strokes than heart attacks.
Counterbalancing the observed benefits, however, was a 40% increase in the risk of gastrointestinal bleeding caused by the aspirin. That increase was expected and is similar to the risk for men, Buring said.
The team also observed a slight increase in hemorrhagic strokes, the less common form of stroke, caused by bleeding into the brain.
"The bottom line is that, for younger women, it's not clear that there would be an overall benefit," Buring said.
Guidelines from the American Heart Assn., issued a year ago, recommend against prescribing aspirin for healthy women until studies of its efficacy have been completed.
"The findings from this trial support that recommendation in women under the age of 65," said Dr. Lori Mosca of Columbia University, chairwoman of the group that wrote the association's guidelines.
When the team looked at the data among women older than 65, a much different picture emerged. In this group, which accounted for about 10% of the study population and one-third of all heart attacks, the risk of stroke was reduced 30% and the risk of heart attack 34%.
"For those age 65 and older, that's where we may see it being useful," Buring said.
The recommendations for elderly women should be exactly the same as those for men, Buring said: If you have at least a 6% increase in cardiovascular risk from smoking, high cholesterol, family history, obesity or other factors, you should be taking one baby aspirin a day.
Mosca cautioned that aspirin should not automatically be given to elderly women.
While the findings "do suggest that in healthy women over 65 we should be considering low-dose aspirin, we will have to balance this benefit with the risk of serious gastrointestinal bleeding and the potential for increasing hemorrhagic strokes," she said.
Researchers had not expected to find such a strong gender difference, said Dr. Elizabeth G. Nabel, director of the National Heart, Lung and Blood Institute, which helped pay for the study -- and it is not clear what causes the difference.
Some speculate that it reflects protection by circulating estrogen in the younger women.
The new findings do not apply to patients who have heart disease or who have already had a heart attack. For those patients, multiple studies of men and women have shown the value of aspirin in preventing further damage.
Taking aspiring while a heart attack is in progress is also valuable for both sexes.
The study was published online Monday by the New England Journal of Medicine and will appear in the March 31 print edition.