Effect of Aspirin Dosage on Stroke Risk in Women
Abstract & commentary
Source: Iso H, et al. Prospective study of aspirin use and risk of stroke in women. Stroke 1999;30:1764-1771.
Several randomized clinical trials have established the benefit of low-dose aspirin in the secondary prevention of ischemic stroke in both men and women (The SALT Collaborative Group. Lancet 1991; 338:1345-1349; Drener HC, et al. J Neurol Sci 1996; 143:1-13; UK-TIA Study Group. J Neurol Neurosurg Psychiatry 1991;54:1044-1054). The role of aspirin in primary prevention of stroke is uncertain, especially in women. Two trials in men were inconclusive but suggested a possible excess risk of disabling stroke (Peto R, et al. BMJ 1988;296:313-316) or cerebral hemorrhage (The Steering Committee of the Physicians’ Health Study Research Group. N Engl J Med 1989;321:129-135) in the aspirin group.
Iso and colleagues previously analyzed six years’ prospective data from the Nurses’ Health Study (Manson JE, et al. JAMA 1991;266:521-527) and found no significant relation between aspirin use and the risk of ischemic or hemorrhagic stroke. In the present study, they report on 14 years’ follow-up in the Nurses’ Health Study cohort. The number of incident strokes (n = 503, 295 ischemic, 100 subarachnoid hemorrhages, 52 intraparenchymal hemorrhages, and 56 type undetermined) permitted a reinvestigation of the relation of aspirin use to stroke subtypes. The participants were classified into five groups of aspirin use as reported on questionnaires in 1980, 1982, 1984, and 1988 (see Table). Women who took 1-6 aspirin per week had a lower risk of large-artery occlusive infarction than women who took no aspirin; the multivariate relative risk was 0.50 (95% CI 0.29-0.85; P = 0.01). The reduction was of greater magnitude for older, hypertensive, or smoking women than for younger, nonhypertensive, or nonsmoking women.
In contrast, women who took 15 or more aspirin per week had a two-fold excess risk of subarachnoid hemorrhage (SAH), the multivariate relative risk was 2.02. The elevation in SAH with aspirin was more apparent for older or hypertensive women than for younger or nonhypertensive women. Aspirin use was not associated with risk of other subtypes of stroke, such as embolic or lacunar infarction.
| Table Strokes in 79,319 Women From 1980-1994, According to Aspirin Use | |||||
| Aspirin Per Week, n | |||||
| 0 | 1-2 | 3-6 | 7-14 | ³ 15 | |
| Women, n | 19,233 | 24,702 | 11,258 | 7900 | 4694 |
| All Strokes | 201 | 114 | 60 | 87 | 41 |
| Ischemic Strokes | 118 | 74 | 34 | 52 | 17 |
| Embolic Infarcts | 12 | 10 | 4 | 5 | 2 |
| Large Artery Occlusive Infarction | 41 | 15 | 7 | 15 | 4 |
| Lacunar Stroke | 48 | 35 | 18 | 31 | 8 |
| Hemorrhagic Stroke | 61 | 31 | 22 | 22 | 16 |
| Subarachnoid Hemorrhage | 37 | 23 | 15 | 13 | 12 |
Commentary
This observational study in middle-aged women found that the effect of aspirin varied according to the dosage. The regular intake of 15 or more aspirin weekly increased the risk of SAH. SAH is the only subtype of stroke that is more prevalent in women than in men. The excess risk of SAH in women taking large amounts of aspirin was two-fold over all, and three-fold among older and hypertensive women. Iso et al speculate that high-dose aspirin, by producing a combined inhibitory effect on both the synthesis of thromboxane A2 in platelets and of prostacyclin in vascular endothelial cells, leads to an increased bleeding tendency and to vasospasm, respectively. Iso et al postulate that spasm in cerebral arteries may increase hemodynamic stress at vulnerable sites for the development and rupture of saccular aneurysms.
In contrast, the weekly intake of 1-6 aspirins reduced the risk of large artery occlusive infarction. Extrapolation of these data to men seems warranted and, therefore, physicians are justified in recommending daily low-dose aspirin to their patients of either sex for the prevention of atherothrombotic stroke. Likewise, the chronic, excessive use of aspirin for the treatment of arthritis and headaches should be avoided. —jjc
Aspirin affects the risk of which types of strokes in women?
a. Embolic stroke
b. Lacunar infarcts
c. Large artery occlusive infarcts
d. Subarachnoid hemorrhage
e. Both c and d
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