From the publishers of The New England Journal of Medicine

The Story

      It is estimated that 20 percent of Americans over age 65 take aspirin regularly for pain relief or to reduce the risk of heart attacks and strokes. Two large, well-respected studies of male physicians have shown that aspirin's blood-thinning effect does indeed reduce the risk of heart attacks in healthy men over age 50. In fact, many physicians now recommend an aspirin a day for their middle-aged and elderly patients, even if they have no apparent risk factors for heart disease.
      The evidence on aspirin for stroke prevention is less clear. One recent analysis of over 100 studies found that regular aspirin use reduces strokes caused by blood clots in the brain (ischemic stroke) by about 25 percent in people at high risk for these events. However, other research suggests that regular aspirin use may actually increase the risk for hemorrhagic stroke -- a type of stroke caused by bleeding in the brain.
      To better understand the risks and benefits of aspirin for stroke prevention in adults, researchers combined data from five previously completed trials involving more than 52,000 people. The participants -- 80 percent of whom were men, primarily in their 50s or 60s -- were followed for an average of 4.6 years. Of those who took aspirin, more than 80 percent took either 75 milligrams of aspirin daily or 325 mg. every other day. The rest took doses of 500 to 650 mg. daily.
      The results, reported in the March Archives of Neurology, are consistent with earlier studies in one major respect: Regular aspirin use reduced heart attacks by about 25 percent. Overall, however, aspirin therapy did not prevent strokes, and it increased the risk of hemorrhagic stroke by 35 percent. How can you navigate the trade-off between aspirin's proven cardiac benefit and its apparent downside regarding stroke? -- The Editors

The Physician's Perspective

Dana Leifer, M.D.

      The finding that low doses of aspirin, taken regularly, significantly reduce the risk of heart attacks in healthy men ranks as a landmark discovery in preventive medicine. But questions remain about who benefits most from regular aspirin use and what dose is best. As the Archives of Neurology study illustrates, the role of aspirin for stroke prevention in healthy people who do not have vascular disease is not clear.
      This single analysis of other studies (called a meta-analysis) found that aspirin did little to reduce stroke risk overall, even for people with known risk factors such as diabetes and high blood pressure. While finding that heart attack risk was reduced among aspirin takers, the meta-analysis found a 35 percent increase in the risk of hemorrhagic stroke. (Hemorrhagic strokes account for about 10 percent of all strokes.)
      These findings need to be interpreted with caution for several reasons. First, the overall number of hemorrhagic strokes within the meta-analysis was very small -- less than 0.4 percent of the participants had one. Second, the vast majority of the participants were male, so the results may not apply to women. Third, the participants were in their mid-50s on average, when men are most vulnerable to heart attacks; strokes generally occur about a decade later. So aspirin may have more benefit in older people in whom the risk of ischemic stroke is higher. Finally, aspirin dosage varied greatly among the studies included in the meta-analysis. It is therefore difficult to draw any conclusions as to what dose, if any, is optimal for reducing stroke risk.
      Another study, which appeared in the April 10 Archives of Internal Medicine, provides additional insight into the role of aspirin in reducing the risk of coronary events and stroke. This study investigated the effects of aspirin in healthy male physicians with no prior history of heart attacks or strokes. Researchers stopped the study when they found a 44 percent reduction in heart attacks among men taking aspirin.
      The men who took aspirin (325 mg.) voluntarily on more than 180 days per year after this study was halted had a 28 percent reduction in heart attacks, compared with nonusers. There was little effect on ischemic stroke among regular aspirin users, but there was a trend toward fewer fatal strokes in men who took aspirin. This study suggests that low doses of aspirin may reduce the severity of strokes and thereby reduce deaths from strokes. Here again, though, the total number of strokes was very small, and there was an increase in the number of brain hemorrhages among aspirin users.
      In view of these findings, is aspirin therapy advisable for apparently healthy adults? The benefits of taking aspirin at low doses -- less than 325 mg. daily -- to reduce heart attack risk probably outweighs the possible increase in the risk of hemorrhagic stroke. Most experts now recommend low-dose aspirin (75 to 81 mg. daily -- equivalent to one baby aspirin) for apparently healthy middle-aged people with risk factors for heart disease and stroke. Although the data are less clear for middle-aged people without apparent risk factors for heart disease or stroke, aspirin may at least reduce the risk of heart disease and possibly also reduce the chance of fatal strokes in these individuals. Of course, you should check with your doctor before starting to take aspirin regularly.
      Aspirin at any dose is generally inadvisable for people taking other blood-thinning medications, as it can increase the chance of gastrointestinal bleeding and bleeding in the brain. If you choose to take aspirin, enteric-coated aspirin is recommended because it may cause less stomach irritation than uncoated aspirin.

(Dana Leifer, M.D., is chief of vascular neurology at North Shore University Hospital in Manhasset, New York, and associate professor of neurology at New York University School of Medicine.)