NEW YORK (Reuters Health) – Atrial fibrillation (AF) increases stroke risk to a greater extent in women than in men, especially in women older than 75 and regardless of their risk profile and use of warfarin, according to a report released online today in JAMA.
“Previously, there was a common believe that women were undertreated with anticoagulation, and this was the cause for the higher risk of stroke among women. Our current paper shows that this is not the situation, as women fill prescription for warfarin in similar proportions to men in the ‘real life’ setting,” first author Dr. Louise Pilote, from McGill University Health Center in Montreal, Canada, told Reuters Health by email.
Dr. Margaret C. Fang from the University of California, San Francisco, who was not involved in the study, told Reuters Health the findings “essentially reinforce previous findings” of higher stroke risk in women with AF relative to men.
The 14% higher risk reported by this paper “is somewhat more modest compared to the risks identified in other populations (which were closer to 60% higher), possibly due to differences in the populations and risk factors and defined outcomes. Nevertheless, the results are largely confirmatory of prior studies,” Dr. Fang said.
Dr. Pilote said the results suggest that the current treatment for women with AF “is not sufficient, especially for older women. New strategies such as including sex in the risk scores should be applied to better prevent stroke in the population of patients with AF, and in particular in the population of older women who are often less recruited for clinical trials for new drugs.”
In the meantime, she added, “the therapeutic level of women on Coumadin should be maximized.”
Using administrative data, Dr. Pilote and colleagues compared patterns of warfarin use and risk of subsequent stroke between 39,398 men and 44,115 women admitted to the hospital with recently diagnosed AF. All of them were at least 65 years old.
Upon admission, women were older (74% were older than 75 years, compared with 61% of men) and had a higher CHADS2 score than men (congestive heart failure, hypertension, age 75 years or older, diabetes mellitus, prior stroke or transient ischemic attack).
One month after being discharged, slightly more women than men filled a prescription for warfarin (61% and 58%). In multivariate analysis, women tended to have more prescriptions filled for warfarin within 30 days postdischarge compared to men (odds ratio 1.07; p<0.001).
At one year, the proportions of warfarin prescriptions filled were slightly increased to 68% in women and 64% in men. In general, “adherence to warfarin was good in both sexes, represented by a mean medication possession ratio of 80% or greater,” the authors say.
According to the researchers, crude stroke rates were significantly higher in women compared with men (5.8% vs 4.3%). The overall incidence of stroke per 100 person-years was 2.02 in women vs 1.61 in men (p<0.001). The difference between sexes was mainly driven by the population of patients older than 75 years.
In multivariable Cox regression analysis, women had a higher risk of stroke than men (adjusted hazard ratio 1.14; p <0.001), even after adjusting for baseline comorbid conditions, individual components of the CHADS2 score and warfarin treatment.
“Women still have higher risk for stroke regardless of warfarin prescriptions perhaps because the INR level is not maximized or other forms of anticoagulation are better in women than men,” Dr. Pilote commented. “The increased risk may be attributable to differences in physiology, vascular biology, genetic factors, hormonal, thromboembolic factors, or psychosocial factors that differ between men and women.”
Dr. Fang said, “An important clinical issue is whether women with AF should be treated differently than men, given their apparently higher stroke risk.” In terms of risk scores, the CHADS2 and CHA2DS2-VASC scores “seem to have similar ability to predict stroke, but one difference is that the CHA2DS2-VASC score includes as a risk factor being female.”
“In general, my take is that among patients in whom the risks vs. benefits of anticoagulation are fairly balanced, the presence of some of these additional risk factors (like being female) might help sway the decision in favor of anticoagulation.” Dr. Fang said. “I am also interested to see whether there are sex-related differences in stroke outcomes in patients who are taking newer anticoagulants such as dabigatran or rivaroxaban.”
The study was supported by the Canadian Institute of Health Research.