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Aug. 20, 2006
News this month A large study recently revealed that taking regular, small doses of aspirin might reduce the risk of having a nonfatal first-time stroke for women 45 years and older. Several earlier studies had shown that taking low doses of aspirin every day decreases men's risk of first-time heart attack but it has little effect on their risk of first-time stroke. Researchers at Brigham and Women's Hospital in Boston wanted to know what effect low doses of aspirin would have on heart attack and stroke potential in women. "Women who took the small doses of aspirin had a 17 percent reduction in risk of stroke overall, but no significant change in their risk of heart attack, compared with the women who took the placebos."
They randomly assigned almost 40,000 American women (45 years and older) to either 100 mg of aspirin or a placebo to be taken every other day, and monitored their health for 10 years. What they found was the opposite of the result in men. Women who took the small doses of aspirin had a 17 percent reduction in risk of stroke overall, but no significant change in their risk of heart attack, compared with the women who took the placebos. When strokes (or brain attacks) occur, blood flow to portions of the brain is interrupted. There are two major types of strokes. An ischemic stroke occurs when a blood clot blocks a blood vessel in the brain. A hemorrhagic stroke occurs when a blood vessel in the brain bursts and blood spills into surrounding tissue. This study revealed that the 100 mg dose of aspirin every other day caused a 24 percent drop in the risk of ischemic stroke, which is the more common kind of stroke, and an insignificant increase in the risk of hemorrhagic stroke, hence the overall reduction in stroke risk of 17 percent. The biggest benefit of aspirin use was found in women who were 65 or older at the start of the study. Of those women, who comprised 10 percent of the study population, the aspirin-takers had a 26 percent lower risk of major cardiovascular events. In addition, they were the only subgroup for whom aspirin also significantly reduced the risk of heart attack. "The biggest benefit of aspirin use was found in women who were 65 or older at the start of the study. Of those women, who comprised 10 percent of the study population, the aspirin-takers had a 26 percent lower risk of major cardiovascular events."
The study also showed a bigger benefit of aspirin in reducing stroke risk in women who never smoked or were former smokers. On the flip side, there was an increased risk of stroke among current smokers. And the aspirin takers reported significantly more gastrointestinal (GI) bleeding and peptic ulcers than the women who took placebo. There were 127 occurrences of GI bleeding that required transfusion in the aspirin group, as compared with 91 in the placebo group. There was no significant difference between the risk of fatal strokes between the aspirin-takers and the women who took the placebo. The study took place between 1992 and 2004 and involved 39,876 healthy women over the age of 45. When they enrolled in the study, the women had no history of major chronic illness, such as cancer, coronary heart disease or cerebrovascular disease, and no history of side-effects to any of the study medications. They were not taking aspirin or nonsteroidal anti-inflammatory medications more than once a week, or were willing to forego their use during the trial. They also were not taking individual supplements of vitamin A, E or beta carotene more than once a week. Every 12 months, the study participants received 12 calendar packs of either aspirin or the placebo, and questionnaires about their compliance with the study and their health. The results were published in the New England Journal of Medicine in March 2005.
Yale-New Haven Hospital is home to a certified Primary Stroke Center
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 Aspirin, along with other measures, may help women fend off stroke The Women's Health Study is provocative for several reasons. First, most subjects in previous large-scale aspirin primary prevention trials were men. Second, the conclusions generated from this study appear to contradict previous randomized trials of aspirin and primary prevention [preventing a first-time stroke]. Finally, this study puts to rest the notion that stroke is a man's disease. “This study puts to rest the notion that stroke is a man's disease"”
A recent meta-analysis evaluation of five large-scale randomized trials involving 55,580 subjects demonstrated that there was no statistical benefit for aspirin therapy in the primary prevention of stroke. However, there may be problems with generalizing the findings from these studies. For instance, women were excluded from three of these studies. In addition, most subjects were males, who were more likely to have a myocardial infarction than stroke. In addition, one major study did not document the frequency of head scans to diagnose stroke. The Women's Health Study (WHS) provides a twist in the uncertainty of whether aspirin is beneficial for the primary prevention of stroke. The study was a randomized, double-blind trial of low-dose aspirin (100 mg every other day) and placebo among 39,876 apparently healthy women aged 45 years or older. The subjects were followed over a 10-year period. Interestingly, the women who took aspirin had a risk reduction of 24% in primary stroke. The results differ from previous studies on the basis of gender. Is this surprising? Perhaps not. Atherosclerosis is known to occur later in women than men. Also, women may be predisposed to atherosclerosis occurring in cerebral arteries as opposed to coronary arteries. In addition, there appear to be differences in how men and women react to aspirin. Finally, the exact relationship between estrogen and thrombosis as it relates to stroke is complex and not entirely understood. The dosing of aspirin in the study was unusual (100 mg every other day) and lower than previous primary prevention studies. Nevertheless, the dose was efficacious enough to reduce the risk of stroke. From previous evidence-based data regarding secondary prevention [preventing a second stroke in a person who has already had one] and aspirin, we know that a baby aspirin (81 mg) is not more effective than full dose aspirin (325 mg) in preventing recurrent stroke. Furthermore, the risk of bleeding is slightly higher when taking a full-dose aspirin. So, what should women take from this study? “Although this study demonstrated that low-dose aspirin reduced the risk of a first stroke in women, aspirin is not appropriate for all women.”
Second, it is important to recognize risk factors for stroke. The most important include hypertension, cigarette smoking, diabetes, atrial fibrillation, high cholesterol and carotid artery disease. Updated guidelines endorsed by the American Heart Association for the primary prevention of stroke endorse the use of a risk assessment tool such as the Framingham Stroke Profile. This can be found at this site. Third, although this study demonstrated that low-dose aspirin reduced the risk of a first stroke in women, aspirin is not appropriate for all women. It is important to note that patients on aspirin had a higher risk of gastrointestinal bleeding and other bleeding. Each person should ask their primary care physician, cardiologist or neurologist if aspirin is right for them. Aspirin may be appropriate in women who are over 45, have risk factors for stroke and no predisposition for bleeding. And finally, patients should work closely with their doctors to understand the risks of stroke and the risks of aspirin therapy. Aspirin is not a panacea. Any medical therapy should be done in conjunction with a lifestyle program that reduces overall vascular risk such as a healthy diet and exercise. Feel free to contact us by email: stroke.center@yale.edu. 
Dr. Schindler is the clinical director of the Yale-New Haven Stroke Center and an instructor in neurology at the Yale University School of Medicine.
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