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Aspirin May Lessen Long-Term Stroke Risk After Preeclampsia

Long-term risk of stroke was lower in women who took aspirin after experiencing preeclampsia and other hypertensive disorders of pregnancy, a prospective U.S. cohort study found.

Women with preeclampsia and related disorders who did not use aspirin regularly showed 1.5-fold higher risk of stroke before age 60, compared to women not having a history of such conditions, reported Eliza Miller, MD, of Columbia University in New York City, and colleagues in Neurology.

However, the group found, stroke risk was not increased among women with preeclampsia who did use aspirin, compared to the non-preeclampsia group.

Preeclampsia and other hypertensive disorders of pregnancy have been linked to increased rates of chronic hypertension and other cardiovascular risks in prior research, but this is the first prospective U.S. study to look specifically at stroke, Miller said.

“Stroke is now the third leading cause of death in U.S. women, compared to the fifth leading cause in men, so it’s really important that we look at sex-specific risk factors and take those into account in our overall assessment of a woman’s risk of future stroke,” Miller told MedPage Today. “While this is an observational study and isn’t strong enough evidence to change practice, it does raise questions about how aggressively we should be treating women in middle age who have a history of these disorders.”

During pregnancy, aspirin reduces preeclampsia incidence in high-risk women, but it typically is discontinued after pregnancy, she noted. Guidelines for estimating 10-year cardiovascular risk to inform primary prevention do not consider preeclampsia in their risk calculations, Miller added.

The analysis looked at women in the California Teachers Study who were ages ≤60 when they enrolled during 1995-1996, and who were followed up prospectively for validated stroke outcomes through 2015. Median age at enrollment was 53, and women who did not report a prior stroke on a baseline questionnaire were included in the analysis. Of 83,749 women in the sample, 4,070 (4.9%) had a history of preeclampsia, either self-reported in an early questionnaire (n=3,361), hospital-diagnosed (n=972), or both (n=262).

Over a mean follow-up of 18.1 years, there were 123 admissions for stroke in the preeclampsia group (3.0%, event rate 166 per 100,000 woman-years) compared with 1,823 (2.3%, 127 per 100,000 woman-years ) in the non-preeclampsia group (P=0.002). Women with pre-eclampsia history had an increased risk of all stroke, even after adjusting for their increased prevalence of risk factors (adjusted HR 1.3, 95% CI 1.2–1.4).

Overall, the pre-eclampsia group showed no increase in stroke risk before age 60 (adjusted HR 1.2, 95% CI 0.9–1.7). But in stratified analyses, women with preeclampsia history who were regular aspirin users had a lower risk of stroke before age 60 (adjusted HR 0.8, 95% CI 0.4-1.7) than those who did not use aspirin (adjusted HR 1.5, 95% CI 1.0-2.1, P=0.18). This effect was not seen with statins, and aspirin users showed no increased risk for hemorrhagic stroke.

This “is not a definitive study, but rather a first attempt to explore the hypothesis that women who have had hypertensive disorders of pregnancy might benefit from primary preventive therapies directed at stroke,” observed Steven Feske, MD, of Brigham and Women’s Hospital in Boston, and Cheryl Bushnell, MD, MHS, of Wake Forest Baptist Health in Winston-Salem, North Carolina, in an accompanying editorial.

“So, where do we go from here?” they asked. A directed randomized controlled trial is unlikely to detect small effects: “in fact, it required meta-analysis of many trials to establish the benefit of aspirin for secondary stroke prevention,” they wrote.

In prior studies including men and women, aspirin appeared to have no overall benefit for primary prevention, but the Women’s Health Study found a 17% reduction of stroke risk in women ages >45 taking aspirin for primary prevention, Feske and Bushnell noted. While the current findings are too preliminary to drive clinical decision-making, “taking the findings of the Women’s Health Study into consideration, the use of aspirin for primary prevention in women ages >45 years of age is reasonable, increasingly so as they accumulate risk factors,” they wrote.

Miller and colleagues noted several study limitations. A small number of strokes occurred in both groups. The researchers used a threshold of P<0.2 for significance for a statistical interaction; this approach may have resulted in increased type 1 errors. Transient ischemic attacks (TIA) and survivor bias may have affected results, and self-reports of preeclampsia history may have introduced misclassification. And women who enrolled in the California Teachers Study were predominantly white and likely to have delayed childbearing to a later age; they may not be representative of all women.

Miller disclosed support from the NIH National Institute of Neurological Disorders and Stroke, the StrokeNet Training Core, and the NIH National Center for Advancing Translational Science. Co-authors disclosed relevant relationships with BMS-Pfizer Alliance for Eliquis, Merck/Organon, and Auxilium.

Feske and Bushnell disclosed no relevant relationships with industry.