Women with atrial fibrillation are at higher risk of stroke than are men with the condition, regardless of their use of warfarin or risk profiles, according to large, population-based cohort study reported in the May 9 issue of JAMA.
In numerous large studies of AF, women’s stroke risk has been shown to be 40%-70% higher than men’s risk. The reason for this discrepancy is unclear, but some have suggested that it might be because women are less likely than men to receive prophylactic warfarin therapy.
The findings of this population-based cohort study disprove this hypothesis and show that warfarin use is not a significant contributor to the discrepancy between the sexes in stroke risk. The results also suggest that "current anticoagulant therapy to prevent stroke might not be sufficient for older women, and newer strategies are needed to further reduce stroke risk in women with AF," said Meytal Avgil Tsadok, Ph.D., of the division of clinical epidemiology, McGill University Health Center, Montreal, and her associates.
The investigators assessed warfarin use and subsequent stroke incidence in a cohort of more than 83,000 elderly patients throughout Quebec who were discharged with a primary or secondary diagnosis of AF in 1998-2007. The 39,398 men and 44,115 women all were aged 65 years and older at admission.
Following hospital discharge, the crude stroke rate was significantly higher in women (5.8%) than in men (4.3%), as was the overall incidence of stroke: 2.02/100 person-years among women, compared with 1.61/100 person-years among men.
In a multivariate analysis that adjusted for comorbid conditions, stroke risk factors, and warfarin use, the higher risk of stroke among women persisted, with a hazard ratio of 1.14, the researchers said (JAMA 2012;307:1952-8).
Women were slightly more likely to fill warfarin prescriptions, with a rate of 60.6%, than were men (58.2% rate). Adherence to warfarin therapy was judged to be good in both sexes, and neither warfarin use nor adherence level affected the discrepancy between men and women in stroke risk.
Other than female sex, the strongest independent risk factor for stroke was a history of the disorder. In an analysis of the subgroup of patients who had no history of stroke, women still were at higher risk than men, with a hazard ratio of 1.17.
"The difference between the sexes was mainly driven by the rates in older (greater than 75 years) patients (2.38/100 person-years for women vs 1.95 in men)," Dr. Avgil Tsadok and her colleagues said.
"Thus, women older than 75 years represent the most important target population for stroke prevention in patients with AF, and the effectiveness of novel anticoagulants in this population in real-world practice will need to be closely monitored," they added.
This study was supported by the Canadian Institutes of Health Research. No relevant financial conflicts of interest were reported.