Female sex as a risk factor for stroke in atrial fibrillation: a nationwide cohort study.

Department of Cardiology, Copenhagen University Hospital Gentofte, Hellerup, Denmark.
Journal of Thrombosis and Haemostasis (Impact Factor: 6.08). 07/2012; 10(9):1745-51. DOI: 10.1111/j.1538-7836.2012.04853.x
Source: PubMed

ABSTRACT Female sex has been suggested as a risk factor for stroke/thromboembolism in patients with non-valvular atrial fibrillation (AF) and has therefore been included within risk scores, e.g., the CHA2 DS2 -VASc score, and guidelines.
To investigate the risk of stroke/thromboembolism associated with female sex in non-valvular AF patients.
Using the national Danish registers, we identified non-anticoagulated patients discharged with non-valvular AF (1997-2008), and subdivided the population into three age intervals: < 65, 65-74 and ≥ 75 years. We calculated stroke rates according to sex, and assessed the stroke risk associated with female sex by using Cox regression analysis.
We included 87,202 AF patients, and 44,744 (51.3%) were female. The rate of stroke/thromboembolism for females aged < 65 and 65-74 years was not increased as compared with men, whereas the rate for females aged ≥ 75 years was increased. At both 1-year and 12-year follow-up, female sex did not increase the risk of stroke for patients aged < 75 years. At 1-year follow-up, the hazard ratios associated with female sex were 0.89 (95% confidence interval [CI] 0.70-1.13) and 0.91 (95 CI 0.79-1.05) for patients aged < 65 and 65-74 years, respectively, and being female and aged ≥ 75 years was associated with an increased risk of stroke of 1.20 (95 CI 1.12-1.28).
Female sex was only associated with an increased risk of stroke for AF patients aged ≥ 75 years. Our study suggests that female sex should not be automatically included as an independent stroke/thromboembolic risk factor in guidelines or in the CHA2 DS2 -VASc score, without careful prior consideration of the 'age < 65 and lone AF' criterion.

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    ABSTRACT: Background—Among patients with atrial fibrillation (AF), women are at higher risk of stroke than men. Using prospective cohort data from a large global population of patients with nonvalvular AF, we sought to identify any differences in the use of anticoagulants for stroke prevention in women and men. Methods and Results—This was a prospective multicenter observational registry with 858 randomly selected sites in 30 countries. A total of 17 184 patients with newly diagnosed (≤6 weeks) nonvalvular AF and ≥1 additional investigator-defined stroke risk factor(s) were recruited (March 2010 to June 2013). The main outcome measure was the use of anticoagulants (vitamin K antagonists, factor Xa inhibitors, and direct thrombin inhibitors) for stroke prevention at AF diagnosis. Of 17 184 patients enrolled, 43.8% were women. More women than men were at moderate-to-high risk of stroke (CHADS2 score ≥2: 65.1% versus 54.7%). Rates of anticoagulant use were not different overall (60.9% of men versus 60.8% of women) and in patients with a CHADS2 score ≥2 (adjusted odds ratio for women versus men, 1.00; 95% confidence interval, 0.92–1.09). In patients at low risk (CHA2DS2-VASc of 0 in men and 1 in women), 41.8% of men and 41.1% of women received an anticoagulant. In patients at high risk (CHA2DS2-VASc score ≥2), 35.4% of men and 38.4% of women did not receive an anticoagulant. Conclusions—These contemporary global data show that anticoagulant use for stroke prevention is no different in men and women with nonvalvular AF. Thromboprophylaxis was, however, suboptimal in substantial proportions of men and women, with underuse in those at moderate-to-high risk of stroke and overuse in those at low risk.
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    ABSTRACT: Several studies have demonstrated sex differences in risk of thromboembolism and death among patients with atrial fibrillation, but it is unclear to what extent these associations relate to actual physiological differences. To date, no study has investigated sex differences with concomitant control for lifestyle related factors known to influence stroke risk. We used data from the Danish Diet, Cancer and Health study, including 57,053 participants (52% female) aged 50-64 years. The study population for this study included the 2,895 patients (36% female) with incident atrial fibrillation after inclusion. Data were linked to outcomes identified using nationwide registries. Risk of thromboembolism and death according to female sex were analysed using Cox proportional hazards models. After a median follow-up of 5.0 years, 137 men and 62 women suffered a thromboembolic event, and 349 men and 151 women died. In a crude analysis, female sex was associated with a non-significant lower risk of thromboembolism (hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.61-1.11). Adjustment for differences in antithrombotic therapy, relevant comorbidities and lifestyle did not change this association (HR 0.77, 95% CI 0.55-1.13). In the final model, female sex was associated with a lower risk of death (HR 0.65, 95% CI 0.51-0.84). The associations were similar in a sensitivity analysis of women not taking hormone replacement therapy, and the effect of hormone replacement therapy use within females was non-significant for both endpoints of thromboembolism and death. In conclusion, in a relatively young population of patients with atrial fibrillation, female sex was associated with a lower risk of thromboembolism and death.
    Thrombosis and haemostasis. 07/2014; 112(4).
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    ABSTRACT: Stroke prevention is central to the management of patients with atrial fibrillation (AF). As effective stroke prophylaxis essentially requires oral anticoagulants, an understanding of the risks and benefits of oral anticoagulant therapy is needed. Although AF increases stroke risk 5-fold, this risk is not homogeneous. Many stroke risk factors also confer an increased risk of bleeding. Various stroke and bleeding risk-stratification schemes have been developed to help inform clinical decision-making. These scores were derived and validated in different study cohorts, ranging from highly selected clinical-trial cohorts to real-world populations. Thus, their performance and classification accuracy vary depending on their derivation cohort(s). In the present review, we provide an overview of currently available stroke and bleeding risk-stratification schemes. We particularly focus on the CHA2DS2-VASc and HAS-BLED schemes, as these are recommended by the latest European guidelines on AF management. Other risk-stratification schemes (eg, CHADS2, R2CHADS2, ATRIA, HEMORR2HAGES, QStroke) and their place in the decision-making are also considered.
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