For Women, Low Doses
Prevent Strokes But Not Heart Attacks; Balancing the Benefits and Risks
By RON WINSLOW
Staff Reporter of THE WALL STREET JOURNAL
March 8, 2005; Page D1

A major new study suggests that aspirin affects women and men differently when it comes to preventing heart attacks and strokes.

Researchers said a 10-year trial -- involving nearly 40,000 women aged 45 and older -- found that a regular every-other-day regimen of low dose aspirin was effective in preventing a first stroke. However, it didn't have any effect in helping avoid a first heart attack. The women in the study had no history of cardiovascular disease.

That is just the opposite of several previous studies involving mostly men: For them, low-dose aspirin is a potent strategy for preventing a first heart attack. But, if anything, it may slightly increase the risk of strokes.

THE BENEFITS OF ASPIRIN

What researchers know about aspirin:

• For women, aspirin helps prevent a first stroke, but not a first heart attack.

• For men, just the opposite was true.

• Patients seeking a stroke benefit need to weigh an increased risk of bleeding.

• Among women, those 65 and older are helped most.




Millions of men have been taking regular doses of aspirin to protect their hearts since a landmark physicians' health study on the benefits of aspirin was published in 1989. Millions of women have been doing the same, taking it on faith that what worked for men would work for them too.

The upshot of the new research: While a person's age and health condition have always been a factor in whether to take aspirin preventively, gender is now a factor as well. For healthy women younger than 65, the benefits of taking aspirin regularly are limited, so it is important to weigh the benefits against the risks. The main problem with aspirin is an elevated risk of stomach bleeding and brain hemorrhage, a factor that the study underscored for women.

For healthy women 65 and older, the benefits of aspirin generally outweigh the risks. However, because of the risk of bleeding problems shown in the study, they too should discuss their individual situation with their doctors.

Women of all ages who have already had cardiac events will probably be advised by their doctors to continue taking aspirin regularly. And the advice for men taking aspirin regularly will not change as a result of the study. Healthy men with an elevated risk of heart disease should consider taking aspirin, with the advice of a doctor.

The study, published yesterday in the New England Journal of Medicine, doesn't suggest any changes in the aspirin regimen for men or for women already diagnosed with heart disease.

Researchers stopped short of concluding that gender explained the differences, saying the issue requires further study. They didn't have any ready explanation for why such differences might exist. Instead, they argued that the bottom line message is similar for either sex. "Whether you're a man or a woman, aspirin reduces your risk of subsequent cardiovascular disease," said Julie Buring, an epidemiologist at Brigham and Women's Hospital, Boston and principal investigator of the study. "But it lowers it for a different reason."

The findings are likely to increase interest in research on how other drugs for other conditions may affect men and women differently.

Dr. Buring presented the findings at the annual meeting of the American College of Cardiology in Orlando. They were published simultaneously online. The study was funded by the National Institutes of Health.

WOMEN'S HEALTH RESOURCES

These groups are pushing to include women in more medical research, and find out how men and women react differently to drugs.

Society for Women's Health Research
Information on women's health policy and clinical studies. A fact sheet lists 10 differences between men and women in conditions such as heart disease, depression, smoking and autoimmune diseases.
www.womenshealthresearch.org

Society for Women's Health Research
Information for women who want to volunteer for medical research.
www.womancando.org

Arizona Center for Research and Education on Therapeutics
Lists drugs that the center says have been shown to expand the QT interval, or resting time of heartbeats, which can have serious or fatal outcomes. Drugs prolonging QT interval can affect women in greater numbers.
www.qtdrugs.org

National Institutes of Health's Office of Research on Women's Health
Lists the agency's 2005 priorities for women's health research, which include studies on mood disorders, autoimmune disorders and cardiovascular systems.
www4.od.nih.gov/orwh/

For women, the benefits of aspirin were relatively modest: a 17% reduction in stroke risk, compared to a 32% reduction in heart-attack risk for men. The stroke benefit was partially offset by an increased risk of rare but serious bleeding events, such as ulcers or brain hemorrhage.

The biggest -- and perhaps the only demonstrable payoff -- for aspirin was for women who were 65 and older when they entered the study. These women accounted for just 10% of study participants, but had one-third of the serious events; however, they were the one group who were also protected against heart attacks.

The bottom line, researchers said, is that benefits of aspirin outweigh the risks for women 65 and older. But the bleeding problems, says Paul Ridker, a cardiologist at Brigham and first author of the study, amount to a "very important clinical caveat." He urged women to discuss their options with their doctors before deciding whether to go on aspirin. For healthy women under 65, he says, "you'd have to look very carefully" at individual risks and benefits.

Aspirin's role in stroke prevention is particularly relevant to women, since they are more likely than men to suffer strokes. Data from the American Heart Association estimate that in 2002, 345,000 women had heart attacks, while 373,000, or 10% more, suffered strokes. By comparison, men had 520,000 heart attacks, and 327,000 strokes.

Importantly, researchers said the new aspirin study doesn't apply to women who have already had heart attacks or heart surgery or have otherwise been diagnosed with coronary artery disease. For such women, as with men, regular low-dose aspirin clearly reduces the likelihood of suffering a subsequent major event or of dying from cardiovascular disease. Similarly, other studies show that for both men and women, taking aspirin at the first sign of chest pain or other heart-attack symptoms significantly improves chances of surviving the episode or limiting its severity.

"The unanswered question was primary prevention," Dr. Buring says -- whether aspirin would help apparently healthy women reduce their risk of a first cardiovascular event. So far, five studies involving about 55,000 patients have addressed that question, but almost exclusively in men. Of the 2,402 heart and stroke-related events documented in those studies and used to calculate the effects of aspirin, just 180 occurred in women.

Indeed, beyond their clinical relevance, the findings underscore the importance of studying the effects of medical interventions in women as well as men. An independent government-supported panel called the U.S. Preventive Services Task recommends routine low-dose aspirin for adults whose risk of having heart attacks over the next 10 years is 6% -- based on such risk factors as age, cholesterol levels, smoking status and blood pressure. The guidelines don't distinguish between men and women.

The American Heart Association had has similar advice for people with a 10% risk. Last year, in issuing guidelines aimed specifically at women, the AHA revised its position, recommending against low dose aspirin for women for heart-attack prevention until further data were available.

Typically, says Sidney Smith, a guidelines expert and cardiologist at University of North Carolina, Chapel Hill, studies involving heart treatments have involved only 10% to 15% women, meaning guidelines based on such data are often based on intuition when applied to women.

---- Heather Won Tesoriero contributed to this article.

Write to Ron Winslow at ron.winslow@wsj.com