Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Sex, Stroke, and Atrial Fibrillation

Sex, Stroke, and Atrial Fibrillation Abstract Context: Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Reasons for this higher stroke risk in women remain unclear, although some studies suggest that undertreatment with warfarin may be a cause. Objective: To compare utilization patterns of warfarin and the risk of subsequent stroke between older men and women with AF at the population level. Design, Setting, and Patients:  Population-based cohort study of patients 65 years or older admitted to the hospital with recently diagnosed AF in the province of Quebec, Canada, 1998-2007, using administrative data with linkage between hospital discharge, physicians, and prescription drug claims databases. Main Outcome Measures:  Risk of stroke. Results: The cohort comprised 39 398 men (47.2%) and 44 115 women (52.8%). At admission, women were older and had a higher CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack) score than men (1.99 [SD, 1.10] vs 1.74 [SD, 1.13], P < .001). At 30 days postdischarge, 58.2% of men and 60.6% of women had filled a warfarin prescription. In adjusted analysis, women appeared to fill more warfarin prescriptions compared with men (odds ratio, 1.07 [95% CI, 1.04-1.11]; P < .001). Adherence to warfarin treatment was good in both sexes. Crude stroke incidence was 2.02 per 100 person-years (95% CI, 1.95-2.10) in women vs 1.61 per 100 person-years (95% CI, 1.54-1.69) in men (P < .001). The sex difference was mainly driven by the population of patients 75 years or older. In multivariable Cox regression analysis, women had a higher risk of stroke than men (adjusted hazard ratio, 1.14 [95% CI, 1.07-1.22]; P < .001), even after adjusting for baseline comorbid conditions, individual components of the CHADS2 score, and warfarin treatment. Conclusion: Among older patients admitted with recently diagnosed AF, the risk of stroke was greater in women than in men, regardless of warfarin use. Sex Differences in Stroke Risk Among Older Patients With Recently Diagnosed Atrial Fibrillation Only a fraction of patients with atrial fibrillation ever have a stroke. Most strokes associated with atrial fibrillation result from embolization of left atrial thrombi. Why do some patients with atrial fibrillation experience cardioembolic stroke while most others do not? Unraveling this mystery would enable physicians to selectively target at-risk patients with effective prevention strategies while avoiding unnecessary exposure of many millions of patients with atrial fibrillation to the inconvenience and risks of bleeding associated with anticoagulant therapy. Understanding the pathogenesis and precipitants of left atrial appendage thrombi in patients with atrial fibrillation has been a holy grail for decades.1 Each of the elements of Virchow's triad has been considered.2 Stasis of blood flow in the left atrial appendage (where the majority of atrial thrombi form) has long been suspected to be the main culprit (“The immobility of the auricular walls makes them defenceless against thrombotic deposits, as a horse should be against flies without his cutaneous muscles”3(p52)). Left atrial flow dynamics and consequent stasis vary widely between patients with atrial fibrillation and over time in individual patients, although the determinants of this variability remain ill defined.4 Endothelial fibrotic remodeling of the left atrial appendage is an active area of research. Prothrombotic diatheses, perhaps intermittent or fluctuating related to surgery or infection, have been postulated, and several identified, but none have been independently or convincingly validated to date.5-7 For more than 2 decades, multivariate analyses of large databases have been undertaken to identify predictors of stroke in patients with atrial fibrillation.8 That women with atrial fibrillation have a higher stroke risk than men first emerged in 19889 and was subsequently confirmed by our analyses of the Stroke Prevention in Atrial Fibrillation trials, which also demonstrated that the increased risk of stroke in women with atrial fibrillation is age related.10,11 Female sex as an independent predictor of stroke in atrial fibrillation has been confirmed by other studies,12-16 with hazard ratios averaging about 1.5, and has been incorporated into several stroke risk stratification schemes used to select patients with atrial fibrillation for anticoagulation prophylaxis.11,12,17 Why do women, and particularly women 75 years or older, with atrial fibrillation have a higher risk of stroke than men, after adjustment for other recognized risk factors? Strokes in older women with atrial fibrillation are particularly likely to be cardioembolic, rather than attributed to the other, less frequent stroke mechanisms from which elderly patients with atrial fibrillation are not spared.10 Differences between the sexes in the hemodynamic impact of atrial fibrillation could theoretically cause increased left atrial stasis in women, but there is no evidence that left atrial dynamics are different in women compared with men.3,18,19 Estrogens are associated with hypercoagulability and increased venous thrombosis risk but this is of limited relevance in patients with atrial fibrillation because the vast majority of affected women are postmenopausal and not receiving hormonal therapy.11,13 Blood stasis is a common risk factor for both left atrial thrombus formation and risk of deep vein thrombosis but, unlike in atrial fibrillation, men are at higher risk of recurrent deep vein thrombosis than women. Avgil Tsadok and colleagues20 provide additional support for sex-based differences in stroke rates in their analyses based on large Quebec, Canada, provincial administrative databases concerning hospitalized patients 65 years or older with recently diagnosed atrial fibrillation. After multivariate adjustment for other stroke predictors in this retrospective cohort study, women overall had a modestly (14%) but significantly higher stroke rate compared with men. There was a significant (P = .02) interaction of age with sex, with the increased stroke risk confined to women 75 years or older. The age-sex interaction on stroke risk in patients with atrial fibrillation was again confirmed recently in a large Swedish nationwide drug registry study.16 We disagree with Avgil Tsadok and colleagues on a key point, that: These results suggest that current anticoagulant therapy to prevent stroke might not be sufficient for older women, and new strategies are needed to further reduce stroke risk in women with AF.20(p1956) The estimated 25% reduction in stroke by warfarin in this study, based on their analysis of administrative databases, clearly underestimates the efficacy of warfarin in women with atrial fibrillation. Pooled results of multiple randomized trials analyzed by rigorous intention-to-treat analysis have demonstrated that treatment with adjusted-dose warfarin reduced ischemic stroke by 67% among women with atrial fibrillation.21 In a randomized trial restricted to those 75 years or older with atrial fibrillation, the reduction in stroke among women was about 35%, but with no interaction of warfarin efficacy with sex.22 It might be argued that estimated efficacy from randomized trials does not represent the “real world”; the large ATRIA cohort of outpatients with atrial fibrillation found a 60% reduction in stroke by warfarin in women.13 Meanwhile, randomized trials indicate that novel oral anticoagulants dabigatran and apixaban also offer highly efficacious protection against stroke for women with atrial fibrillation.23-25 Given the methodologic limitations of estimating the protective effects of warfarin in the current study, we believe that the emphasis of Avgil Tsadok et al on the need for new strategies to prevent stroke among women with atrial fibrillation is premature. In short, the results of the study by Avgil Tsadok et al add to a large body of evidence that women with atrial fibrillation who are 75 years or older are at high risk of cardioembolic stroke that can be effectively prevented by anticoagulation and should receive such therapy if it can be given safely. Adjusted-dose warfarin provides a high degree of protection against stroke for women with atrial fibrillation, at least as high, if not higher, than for men.13,21 The interaction between sex and age lacks a biological explanation, but it is a consistent finding in several studies. After nearly 2 decades of investigation, mechanism of the increased stroke risk among elderly women with atrial fibrillation remains “a riddle, wrapped in a mystery, inside an enigma.”26 Back to top Article Information Correspondence: Dr Hart, Department of Medicine (Neurology), McMaster University, Population Health Research Institute, Hamilton General Hospital, DBCVSRI C3-110, 237 Barton St E, Hamilton, ON L8L 2X2, Canada (robert.hart@phri.ca). Published Online: September 24, 2012. doi:10.1001/archneurol.2012.2691 Author Contributions:Study concept and design: Hart. Analysis and interpretation of data: Eikelboom and Pearce. Drafting of the manuscript: Hart. Critical revision of the manuscript for important intellectual content: Hart, Eikelboom, and Pearce. Study supervision: Hart. Financial Disclosure: None reported. References 1. Halperin JL, Hart RG. Atrial fibrillation and stroke: new ideas, persisting dilemmas. Stroke. 1988;19(8):937-9413041652PubMedGoogle ScholarCrossref 2. Watson T, Shantsila E, Lip GYH. Mechanisms of thrombogenesis in atrial fibrillation: Virchow's triad revisited. Lancet. 2009;373(9658):155-16619135613PubMedGoogle ScholarCrossref 3. Soderstrom N. Myocardial infarction and mural thrombosis in the atria of the heart. Acta Med Scand Suppl. 1948;217:51-52Google Scholar 4. Goldman ME, Pearce LA, Hart RG, et al. Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation, I: reduced flow velocity in the left atrial appendage (the Stroke Prevention in Atrial Fibrillation [SPAF-III] Study). J Am Soc Echocardiogr. 1999;12(12):1080-108710588784PubMedGoogle ScholarCrossref 5. Feinberg WM, Pearce LA, Hart RG, et al. Markers of thrombin and platelet activity in patients with atrial fibrillation: correlation with stroke among 1531 participants in the Stroke Prevention in Atrial Fibrillation III Study. Stroke. 1999;30(12):2547-255310582976PubMedGoogle ScholarCrossref 6. Lip GYH, Lane D, Van Walraven C, Hart RG. Additive role of plasma von Willebrand factor levels to clinical factors for risk stratification of patients with atrial fibrillation. Stroke. 2006;37(9):2294-230016888271PubMedGoogle ScholarCrossref 7. Lip GYH, Patel JV, Hughes E, Hart RG. High-sensitivity C-reactive protein and soluble CD40 ligand as indices of inflammation and platelet activation in 880 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors, stroke risk stratification schema, and prognosis. Stroke. 2007;38(4):1229-123717332453PubMedGoogle ScholarCrossref 8. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007;69(6):546-55417679673PubMedGoogle ScholarCrossref 9. Boysen G, Nyboe J, Appleyard M, et al. Stroke incidence and risk factors for stroke in Copenhagen, Denmark. Stroke. 1988;19(11):1345-13533188119PubMedGoogle ScholarCrossref 10. Stroke Prevention in Atrial Fibrillation Investigators. Risk factors for thromboembolism during aspirin therapy in patients with atrial fibrillation: the Stroke Prevention in Atrial Fibrillation Study. J Stroke Cerebrovasc Dis. 1995;5(3):147-157Google ScholarCrossref 11. Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW.the Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. Stroke. 1999;30(6):1223-122910356104PubMedGoogle ScholarCrossref 12. Wang TJ, Massaro JM, Levy D, et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. JAMA. 2003;290(8):1049-105612941677PubMedGoogle ScholarCrossref 13. Fang MC, Singer DE, Chang Y, et al. Gender differences in the risk of ischemic stroke and peripheral embolism in atrial fibrillation: the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) study. Circulation. 2005;112(12):1687-169116157766PubMedGoogle ScholarCrossref 14. Friberg J, Scharling H, Gadsbøll N, Truelsen T, Jensen GB.Copenhagen City Heart Study. Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (the Copenhagen City Heart Study). Am J Cardiol. 2004;94(7):889-89415464671PubMedGoogle ScholarCrossref 15. Coppens M, Eikelboom JW, Hart RG, et al. The CHA2DS2-VASC score identifies af patients with a CHADS2 score of 0 or 1 treated with antiplatelet therapy who are unlikely to benefit from oral anticoagulant therapy. J Am Coll Cardiol. 2012;59(13s1):E570-E570Google ScholarCrossref 16. Friberg L, Benson L, Rosenqvist M, Lip GYH. Assessment of female sex as a risk factor in atrial fibrillation in Sweden: nationwide retrospective cohort study. BMJ. 2012;344:e352222653980PubMedGoogle ScholarCrossref 17. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation. Chest. 2010;137(2):263-27219762550PubMedGoogle ScholarCrossref 18. Zabalgoitia M, Halperin JL, Pearce LA, Blackshear JL, Asinger RW, Hart RG.Stroke Prevention in Atrial Fibrillation III Investigators. Transesophageal echocardiographic correlates of clinical risk of thromboembolism in nonvalvular atrial fibrillation. J Am Coll Cardiol. 1998;31(7):1622-16269626843PubMedGoogle ScholarCrossref 19. Asinger RW, Koehler J, Pearce LA, et al. Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation, II: dense spontaneous echocardiographic contrast (the Stroke Prevention in Atrial Fibrillation [SPAF-III] Study). J Am Soc Echocardiogr. 1999;12(12):1088-109610588785PubMedGoogle ScholarCrossref 20. Avgil Tsadok M, Jackevicius CA, Rahme E, Humphries KH, Behlouli H, Pilote L. Sex differences in stroke risk among older patients with recently diagnosed atrial fibrillation. JAMA. 2012;307(18):1952-195822570463PubMedGoogle ScholarCrossref 21. van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA. 2002;288(19):2441-244812435257PubMedGoogle ScholarCrossref 22. Mant J, Hobbs FD, Fletcher K, et al; BAFTA investigators; Midland Research Practices Network (MidReC). Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370(9586):493-50317693178PubMedGoogle ScholarCrossref 23. Connolly SJ, Ezekowitz MD, Yusuf S, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-115119717844PubMedGoogle ScholarCrossref 24. Connolly SJ, Eikelboom J, Joyner C, et al; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806-81721309657PubMedGoogle ScholarCrossref 25. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-99221870978PubMedGoogle ScholarCrossref 26. Churchill WS. Radio broadcast. October 1939 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Sex, Stroke, and Atrial Fibrillation

Download PDF
3 pages

Loading next page...
 
/lp/american-medical-association/sex-stroke-and-atrial-fibrillation-WdWVcrWYQZ

References (29)

Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneurol.2012.2691
Publisher site
See Article on Publisher Site

Abstract

Abstract Context: Stroke is a serious complication associated with atrial fibrillation (AF). Women with AF are at higher risk of stroke compared with men. Reasons for this higher stroke risk in women remain unclear, although some studies suggest that undertreatment with warfarin may be a cause. Objective: To compare utilization patterns of warfarin and the risk of subsequent stroke between older men and women with AF at the population level. Design, Setting, and Patients:  Population-based cohort study of patients 65 years or older admitted to the hospital with recently diagnosed AF in the province of Quebec, Canada, 1998-2007, using administrative data with linkage between hospital discharge, physicians, and prescription drug claims databases. Main Outcome Measures:  Risk of stroke. Results: The cohort comprised 39 398 men (47.2%) and 44 115 women (52.8%). At admission, women were older and had a higher CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke or transient ischemic attack) score than men (1.99 [SD, 1.10] vs 1.74 [SD, 1.13], P < .001). At 30 days postdischarge, 58.2% of men and 60.6% of women had filled a warfarin prescription. In adjusted analysis, women appeared to fill more warfarin prescriptions compared with men (odds ratio, 1.07 [95% CI, 1.04-1.11]; P < .001). Adherence to warfarin treatment was good in both sexes. Crude stroke incidence was 2.02 per 100 person-years (95% CI, 1.95-2.10) in women vs 1.61 per 100 person-years (95% CI, 1.54-1.69) in men (P < .001). The sex difference was mainly driven by the population of patients 75 years or older. In multivariable Cox regression analysis, women had a higher risk of stroke than men (adjusted hazard ratio, 1.14 [95% CI, 1.07-1.22]; P < .001), even after adjusting for baseline comorbid conditions, individual components of the CHADS2 score, and warfarin treatment. Conclusion: Among older patients admitted with recently diagnosed AF, the risk of stroke was greater in women than in men, regardless of warfarin use. Sex Differences in Stroke Risk Among Older Patients With Recently Diagnosed Atrial Fibrillation Only a fraction of patients with atrial fibrillation ever have a stroke. Most strokes associated with atrial fibrillation result from embolization of left atrial thrombi. Why do some patients with atrial fibrillation experience cardioembolic stroke while most others do not? Unraveling this mystery would enable physicians to selectively target at-risk patients with effective prevention strategies while avoiding unnecessary exposure of many millions of patients with atrial fibrillation to the inconvenience and risks of bleeding associated with anticoagulant therapy. Understanding the pathogenesis and precipitants of left atrial appendage thrombi in patients with atrial fibrillation has been a holy grail for decades.1 Each of the elements of Virchow's triad has been considered.2 Stasis of blood flow in the left atrial appendage (where the majority of atrial thrombi form) has long been suspected to be the main culprit (“The immobility of the auricular walls makes them defenceless against thrombotic deposits, as a horse should be against flies without his cutaneous muscles”3(p52)). Left atrial flow dynamics and consequent stasis vary widely between patients with atrial fibrillation and over time in individual patients, although the determinants of this variability remain ill defined.4 Endothelial fibrotic remodeling of the left atrial appendage is an active area of research. Prothrombotic diatheses, perhaps intermittent or fluctuating related to surgery or infection, have been postulated, and several identified, but none have been independently or convincingly validated to date.5-7 For more than 2 decades, multivariate analyses of large databases have been undertaken to identify predictors of stroke in patients with atrial fibrillation.8 That women with atrial fibrillation have a higher stroke risk than men first emerged in 19889 and was subsequently confirmed by our analyses of the Stroke Prevention in Atrial Fibrillation trials, which also demonstrated that the increased risk of stroke in women with atrial fibrillation is age related.10,11 Female sex as an independent predictor of stroke in atrial fibrillation has been confirmed by other studies,12-16 with hazard ratios averaging about 1.5, and has been incorporated into several stroke risk stratification schemes used to select patients with atrial fibrillation for anticoagulation prophylaxis.11,12,17 Why do women, and particularly women 75 years or older, with atrial fibrillation have a higher risk of stroke than men, after adjustment for other recognized risk factors? Strokes in older women with atrial fibrillation are particularly likely to be cardioembolic, rather than attributed to the other, less frequent stroke mechanisms from which elderly patients with atrial fibrillation are not spared.10 Differences between the sexes in the hemodynamic impact of atrial fibrillation could theoretically cause increased left atrial stasis in women, but there is no evidence that left atrial dynamics are different in women compared with men.3,18,19 Estrogens are associated with hypercoagulability and increased venous thrombosis risk but this is of limited relevance in patients with atrial fibrillation because the vast majority of affected women are postmenopausal and not receiving hormonal therapy.11,13 Blood stasis is a common risk factor for both left atrial thrombus formation and risk of deep vein thrombosis but, unlike in atrial fibrillation, men are at higher risk of recurrent deep vein thrombosis than women. Avgil Tsadok and colleagues20 provide additional support for sex-based differences in stroke rates in their analyses based on large Quebec, Canada, provincial administrative databases concerning hospitalized patients 65 years or older with recently diagnosed atrial fibrillation. After multivariate adjustment for other stroke predictors in this retrospective cohort study, women overall had a modestly (14%) but significantly higher stroke rate compared with men. There was a significant (P = .02) interaction of age with sex, with the increased stroke risk confined to women 75 years or older. The age-sex interaction on stroke risk in patients with atrial fibrillation was again confirmed recently in a large Swedish nationwide drug registry study.16 We disagree with Avgil Tsadok and colleagues on a key point, that: These results suggest that current anticoagulant therapy to prevent stroke might not be sufficient for older women, and new strategies are needed to further reduce stroke risk in women with AF.20(p1956) The estimated 25% reduction in stroke by warfarin in this study, based on their analysis of administrative databases, clearly underestimates the efficacy of warfarin in women with atrial fibrillation. Pooled results of multiple randomized trials analyzed by rigorous intention-to-treat analysis have demonstrated that treatment with adjusted-dose warfarin reduced ischemic stroke by 67% among women with atrial fibrillation.21 In a randomized trial restricted to those 75 years or older with atrial fibrillation, the reduction in stroke among women was about 35%, but with no interaction of warfarin efficacy with sex.22 It might be argued that estimated efficacy from randomized trials does not represent the “real world”; the large ATRIA cohort of outpatients with atrial fibrillation found a 60% reduction in stroke by warfarin in women.13 Meanwhile, randomized trials indicate that novel oral anticoagulants dabigatran and apixaban also offer highly efficacious protection against stroke for women with atrial fibrillation.23-25 Given the methodologic limitations of estimating the protective effects of warfarin in the current study, we believe that the emphasis of Avgil Tsadok et al on the need for new strategies to prevent stroke among women with atrial fibrillation is premature. In short, the results of the study by Avgil Tsadok et al add to a large body of evidence that women with atrial fibrillation who are 75 years or older are at high risk of cardioembolic stroke that can be effectively prevented by anticoagulation and should receive such therapy if it can be given safely. Adjusted-dose warfarin provides a high degree of protection against stroke for women with atrial fibrillation, at least as high, if not higher, than for men.13,21 The interaction between sex and age lacks a biological explanation, but it is a consistent finding in several studies. After nearly 2 decades of investigation, mechanism of the increased stroke risk among elderly women with atrial fibrillation remains “a riddle, wrapped in a mystery, inside an enigma.”26 Back to top Article Information Correspondence: Dr Hart, Department of Medicine (Neurology), McMaster University, Population Health Research Institute, Hamilton General Hospital, DBCVSRI C3-110, 237 Barton St E, Hamilton, ON L8L 2X2, Canada (robert.hart@phri.ca). Published Online: September 24, 2012. doi:10.1001/archneurol.2012.2691 Author Contributions:Study concept and design: Hart. Analysis and interpretation of data: Eikelboom and Pearce. Drafting of the manuscript: Hart. Critical revision of the manuscript for important intellectual content: Hart, Eikelboom, and Pearce. Study supervision: Hart. Financial Disclosure: None reported. References 1. Halperin JL, Hart RG. Atrial fibrillation and stroke: new ideas, persisting dilemmas. Stroke. 1988;19(8):937-9413041652PubMedGoogle ScholarCrossref 2. Watson T, Shantsila E, Lip GYH. Mechanisms of thrombogenesis in atrial fibrillation: Virchow's triad revisited. Lancet. 2009;373(9658):155-16619135613PubMedGoogle ScholarCrossref 3. Soderstrom N. Myocardial infarction and mural thrombosis in the atria of the heart. Acta Med Scand Suppl. 1948;217:51-52Google Scholar 4. Goldman ME, Pearce LA, Hart RG, et al. Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation, I: reduced flow velocity in the left atrial appendage (the Stroke Prevention in Atrial Fibrillation [SPAF-III] Study). J Am Soc Echocardiogr. 1999;12(12):1080-108710588784PubMedGoogle ScholarCrossref 5. Feinberg WM, Pearce LA, Hart RG, et al. Markers of thrombin and platelet activity in patients with atrial fibrillation: correlation with stroke among 1531 participants in the Stroke Prevention in Atrial Fibrillation III Study. Stroke. 1999;30(12):2547-255310582976PubMedGoogle ScholarCrossref 6. Lip GYH, Lane D, Van Walraven C, Hart RG. Additive role of plasma von Willebrand factor levels to clinical factors for risk stratification of patients with atrial fibrillation. Stroke. 2006;37(9):2294-230016888271PubMedGoogle ScholarCrossref 7. Lip GYH, Patel JV, Hughes E, Hart RG. High-sensitivity C-reactive protein and soluble CD40 ligand as indices of inflammation and platelet activation in 880 patients with nonvalvular atrial fibrillation: relationship to stroke risk factors, stroke risk stratification schema, and prognosis. Stroke. 2007;38(4):1229-123717332453PubMedGoogle ScholarCrossref 8. Stroke Risk in Atrial Fibrillation Working Group. Independent predictors of stroke in patients with atrial fibrillation: a systematic review. Neurology. 2007;69(6):546-55417679673PubMedGoogle ScholarCrossref 9. Boysen G, Nyboe J, Appleyard M, et al. Stroke incidence and risk factors for stroke in Copenhagen, Denmark. Stroke. 1988;19(11):1345-13533188119PubMedGoogle ScholarCrossref 10. Stroke Prevention in Atrial Fibrillation Investigators. Risk factors for thromboembolism during aspirin therapy in patients with atrial fibrillation: the Stroke Prevention in Atrial Fibrillation Study. J Stroke Cerebrovasc Dis. 1995;5(3):147-157Google ScholarCrossref 11. Hart RG, Pearce LA, McBride R, Rothbart RM, Asinger RW.the Stroke Prevention in Atrial Fibrillation (SPAF) Investigators. Factors associated with ischemic stroke during aspirin therapy in atrial fibrillation: analysis of 2012 participants in the SPAF I-III clinical trials. Stroke. 1999;30(6):1223-122910356104PubMedGoogle ScholarCrossref 12. Wang TJ, Massaro JM, Levy D, et al. A risk score for predicting stroke or death in individuals with new-onset atrial fibrillation in the community: the Framingham Heart Study. JAMA. 2003;290(8):1049-105612941677PubMedGoogle ScholarCrossref 13. Fang MC, Singer DE, Chang Y, et al. Gender differences in the risk of ischemic stroke and peripheral embolism in atrial fibrillation: the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) study. Circulation. 2005;112(12):1687-169116157766PubMedGoogle ScholarCrossref 14. Friberg J, Scharling H, Gadsbøll N, Truelsen T, Jensen GB.Copenhagen City Heart Study. Comparison of the impact of atrial fibrillation on the risk of stroke and cardiovascular death in women versus men (the Copenhagen City Heart Study). Am J Cardiol. 2004;94(7):889-89415464671PubMedGoogle ScholarCrossref 15. Coppens M, Eikelboom JW, Hart RG, et al. The CHA2DS2-VASC score identifies af patients with a CHADS2 score of 0 or 1 treated with antiplatelet therapy who are unlikely to benefit from oral anticoagulant therapy. J Am Coll Cardiol. 2012;59(13s1):E570-E570Google ScholarCrossref 16. Friberg L, Benson L, Rosenqvist M, Lip GYH. Assessment of female sex as a risk factor in atrial fibrillation in Sweden: nationwide retrospective cohort study. BMJ. 2012;344:e352222653980PubMedGoogle ScholarCrossref 17. Lip GY, Nieuwlaat R, Pisters R, Lane DA, Crijns HJ. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor-based approach: the Euro Heart Survey on Atrial Fibrillation. Chest. 2010;137(2):263-27219762550PubMedGoogle ScholarCrossref 18. Zabalgoitia M, Halperin JL, Pearce LA, Blackshear JL, Asinger RW, Hart RG.Stroke Prevention in Atrial Fibrillation III Investigators. Transesophageal echocardiographic correlates of clinical risk of thromboembolism in nonvalvular atrial fibrillation. J Am Coll Cardiol. 1998;31(7):1622-16269626843PubMedGoogle ScholarCrossref 19. Asinger RW, Koehler J, Pearce LA, et al. Pathophysiologic correlates of thromboembolism in nonvalvular atrial fibrillation, II: dense spontaneous echocardiographic contrast (the Stroke Prevention in Atrial Fibrillation [SPAF-III] Study). J Am Soc Echocardiogr. 1999;12(12):1088-109610588785PubMedGoogle ScholarCrossref 20. Avgil Tsadok M, Jackevicius CA, Rahme E, Humphries KH, Behlouli H, Pilote L. Sex differences in stroke risk among older patients with recently diagnosed atrial fibrillation. JAMA. 2012;307(18):1952-195822570463PubMedGoogle ScholarCrossref 21. van Walraven C, Hart RG, Singer DE, et al. Oral anticoagulants vs aspirin in nonvalvular atrial fibrillation: an individual patient meta-analysis. JAMA. 2002;288(19):2441-244812435257PubMedGoogle ScholarCrossref 22. Mant J, Hobbs FD, Fletcher K, et al; BAFTA investigators; Midland Research Practices Network (MidReC). Warfarin versus aspirin for stroke prevention in an elderly community population with atrial fibrillation (the Birmingham Atrial Fibrillation Treatment of the Aged Study, BAFTA): a randomised controlled trial. Lancet. 2007;370(9586):493-50317693178PubMedGoogle ScholarCrossref 23. Connolly SJ, Ezekowitz MD, Yusuf S, et al; RE-LY Steering Committee and Investigators. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361(12):1139-115119717844PubMedGoogle ScholarCrossref 24. Connolly SJ, Eikelboom J, Joyner C, et al; AVERROES Steering Committee and Investigators. Apixaban in patients with atrial fibrillation. N Engl J Med. 2011;364(9):806-81721309657PubMedGoogle ScholarCrossref 25. Granger CB, Alexander JH, McMurray JJ, et al; ARISTOTLE Committees and Investigators. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365(11):981-99221870978PubMedGoogle ScholarCrossref 26. Churchill WS. Radio broadcast. October 1939

Journal

Archives of Neurology – American Medical Association

Published: Dec 1, 2012

There are no references for this article.