Does Aspirin Increase the Risk of Hemorrhagic Stroke?
Abstract & Commentary
Synopsis: Aspirin therapy reduced the risk of myocardial infarction and ischemic stroke more than it increased the risk of hemorrhagic stroke.
Source: He J, et al. JAMA 1998;280:1930-1935.
During the past two decades, a number of large randomized, controlled clinical trials have demonstrated that aspirin therapy reduces the risk of subsequent myocardial infarction and stroke, even in healthy populations.1,2 In the Physicians’ Health Study, 22,071 healthy male physicians age 40-84 years were randomly assigned to receive 325 mg of aspirin or placebo every other day and, after an average of 60.2 months of follow-up, 23 hemorrhagic strokes were observed in the aspirin group compared with only 12 cases in the control group;2 aspirin use was, therefore, associated with a 2.14-fold increased risk of hemorrhagic stroke in this study. Aspirin therapy was also associated with an increased risk of hemorrhagic stroke (2.78-fold) in the Swedish Aspirin Low-dose Trial (SALT).3
He and associates performed a meta-analysis to evaluate the relationship between aspirin use and risk of hemorrhagic stroke. They examined data from 16 trials with 55,462 participants in which the mean dose of aspirin was 263 mg per day and the mean duration of treatment was 37 months. Aspirin was associated with highly significant absolute risk reductions in myocardial infarctions and ischemic strokes; however, these studies did also reveal an absolute risk increase in hemorrhagic stroke that proved to be in a statistically significant range. These risk differences were not related to differences in subject or study design characteristics.
Comment by Harold L. Karpman, MD, FACC, FACP
This carefully performed meta-analysis demonstrated that aspirin use is associated with a 15% proportionate reduction in all-cause mortality, a 16% reduction in cardiovascular mortality, a 31% reduction in total myocardial infarctions, and an 18% reduction in ischemic strokes. These results are comparable with the results of a meta-analysis conducted by the Antiplatelet Trialist’s Collaborative Group.4
The significant increase in risk of hemorrhage stroke with the use of aspirin (i.e., an 84% increase in the risk ratio) was a consistent finding in all of the trials even though they were conducted in different populations and used different study designs. It should be noted that the minimum dose of aspirin in the trials that was included in this meta-analysis was 75 mg per day, which is higher than the threshold that effectively eliminates the synthesis of thromboxane A2,5 and, therefore, the use of effective doses of aspirin in all examined trials probably explains why the risk of hemorrhagic stroke proved to be so similar in all of the studies.
In summary, He et al revealed that aspirin therapy reduced the risk of myocardial infarction and ischemic stroke more than it increased the risk of hemorrhagic stroke. From a practical clinical point of view, physicians should carefully determine the risk-benefit ratio of aspirin treatment for prevention of cardiovascular or cerebrovascular disease on an individual basis. For example, in the primary prevention of cardiovascular or cerebrovascular disease, the risk of these events is, on average, much less than in the population of patients who are being given aspirin for secondary prevention, and, therefore, the increased risk of cerebrovascular hemorrhage produced by aspirin therapy in the latter group may well exceed any benefits resulting from aspirin therapy.
Finally, although it has been suggested that the benefit of aspirin varies with the number and types of risk factors for ischemic cardiovascular events that are present in any individual patient, the meta-analysis by He et al supports the concept that the increased risk of hemorr-hagic stroke in patients receiving aspirin therapy is not affected by the presence or absence of any of the various risk factors. Therefore, the risks and benefits of aspirin therapy should be evaluated in light of each patient’s individual risk profile for cardiovascular events and also as to whether such therapy is being administered for primary or secondary prevention of these events. In other words, although aspirin therapy has been demonstrated to reduce the risk of myocardial infarction in those who are at relatively high risk, its benefits may not be worth the risk of cerebrovascular hemorrhage in that population of healthy persons who are younger than 50 years of age.1,2
References
1. Peto R, et al. BMJ 1988;296:313-316.
2. Steering Committee of the Physicians’ Health Study Research Group. N Engl J Med 1989;321:129-135.
3. The SALT Collaborative Group. Lancet 1991;338: 1345-1349.
4. Antiplatelet Trialists’ Collaboration. BMJ 1994;308: 81-106.
5. Willard JE, et al. N Engl J Med 1992;327:175-181.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content