A meta-analysis of more than 95,000 patients has shown that aspirin can significantly reduce the risk of stroke in women, but it appears to have no protective effect in men, according to a new analysis by Duke University Medical Center cardiologists.

Additionally, the researchers found that aspirin increases the risk of bleeding, or hemorrhagic, strokes in men with no effect on women. For the more common form of stroke known as ischemic stroke, in which blood flow to a portion of brain is blocked, aspirin had no effect on men but reduced the incidence in women.

The seemingly conflicting results of this study, along with the results of other studies, should lead to more intensive research into the differences between the genders when it comes to cerebrovascular disease and drugs use to prevent it, the researchers said. They emphasized that both healthy men and women who can tolerate aspirin should be taking the medication, since this analysis demonstrated its effectiveness in preventing strokes in women, and it is already known to reduce heart attacks in men.

“While we’ve known that aspirin is effective in preventing stroke in patients who already have cerebrovascular disease, very little is known about its abilities as a primary prevention method in otherwise healthy people,” said Duke cardiology fellow Jeffrey Berger, M.D., who presented the results of his analysis Nov. 14, 2005, at the annual scientific sessions of the American Heart Association in Dallas.

“Until the advent of the Women’s Health Study (WHS), clinical trials included primarily men and found that aspirin had a positive effect in reducing the risk for heart attacks, but had no effect on stroke,” Berger continued. “So when the WHS found a positive effect for aspirin on stroke prevention in women, it raised the question of whether or not gender has an impact on aspirin’s ability to reduce the risk of stroke.”

In addition to the small numbers of women studied, these earlier clinical trials did not distinguish between the two markedly different types of stroke - ischemic and hemorrhagic.

During a stroke, brain cells are either damaged or killed, with the effects on the patient depending on the size of the damage and where in the brain the damage occurs. The ischemic form of stroke, in which arteries supplying blood to the brain are blocked, represents about 83 percent of all strokes. The hemorrhagic form of stroke, which tends to have more serious consequences for the patient, occurs when blood vessels within the brain burst, leading to a potentially deadly buildup of blood within the brain.

For his analysis on the effects of gender on aspirin’s ability to prevent stroke, Berger combined the data from six different randomized clinical trials, including the WHS, which yielded a total of 95,456 patients, none of whom had coronary artery disease. Of that total, 51,342 were women. The trials all involved the comparison of low-dose aspirin versus placebo for the primary prevention of cardiovascular disease.

“Among the women who were involved in these trials, the use of aspirin was associated with a statistically significant 17 percent reduction in the risk of stroke,” Berger said. “For the men, aspirin use was associated with a non-significant 13 percent increase in stroke risk.”

When Berger concentrated on ischemic stroke, he found that aspirin use was associated with a significant 24 percent reduction in risk in women, compared to no effect for men. For Hemorrhagic stroke, the trends were reversed: aspirin had no significant effect on women, but in men, aspirin was associated with a significant 69 percent increase in risk.

“The reasons or mechanisms behind any gender-based differences in the ability of aspirin to prevent stroke is unclear and requires further investigation,” Berger said. “The bigger question this study raises is that there may be biological differences in how the genders response to other drugs we prescribe patients. This study raises the question for one drug - aspirin.”

Berger said that the findings of this analysis should provide a scientific basis for physicians to prescribe aspirin as a preventative measure for those women who do not suffer from the potential gastrointestinal side effects of the drug.

“As opposed to the situation with men, aspirin tends to be under-prescribed for women,” Berger said. “There is no reason for this to be the case - aspirin is effective, it is inexpensive and easily available.”

According to the American Stroke Association, about 700,000 Americans will suffer a stroke each year, with about 163,000 of them dying, making it the third leading cause of death. About 60 percent of strokes are suffered by women.

Joining Berger in his analysis was his mentor, David Brown, M.D., State University of New York Health Science Center, Stony Brook, NY.

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