This Article Full Text Full Text (PDF) All Versions of this Article: 112/12/1687    most recent CIRCULATIONAHA.105.553438v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fang, M. C. Articles by Go, A. S. Search for Related Content PubMed PubMed Citation Articles by Fang, M. C. Articles by Go, A. S. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Stroke Hazardous Substances DB WARFARIN Related Collections Anticoagulants Arrhythmias, clinical electrophysiology, drugs Epidemiology Risk Factors for Stroke

(Circulation. 2005;112:1687-1691.)
© 2005 American Heart Association, Inc.

Arrhythmia/Electrophysiology

Gender Differences in the Risk of Ischemic Stroke and Peripheral Embolism in Atrial Fibrillation

The AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA) Study

Margaret C. Fang, MD, MPH; Daniel E. Singer, MD; Yuchiao Chang, PhD; Elaine M. Hylek, MD, MPH; Lori E. Henault, MPH; Nancy G. Jensvold, MPH; Alan S. Go, MD

From the University of California, San Francisco (M.C.F., A.S.G.); Clinical Epidemiology Unit, Massachusetts General Hospital, Boston (D.E.S., Y.C., L.E.H.); General Internal Medicine and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Mass (E.M.H.); and Division of Research, Kaiser Permanente of Northern California, Oakland (N.G.J., A.S.G.).

Correspondence to Margaret C. Fang, MD, MPH, Department of Medicine, Hospitalist Group, University of California, San Francisco, 533 Parnassus Ave, Box 0131, San Francisco, CA 94143. E-mail mfang{at}medicine.ucsf.edu

Received April 4, 2005; revision received May 24, 2005; accepted June 2, 2005.

Background— Previous studies provide conflicting results about whether women are at higher risk than men for thromboembolism in the setting of atrial fibrillation (AF). We examined data from a large contemporary cohort of AF patients to address this question.

Methods and Results— We prospectively studied 13 559 adults with AF and recorded data on patients’ clinical characteristics and the occurrence of incident hospitalizations for ischemic stroke, peripheral embolism, and major hemorrhagic events through searching validated computerized databases and medical record review. We compared event rates by patient sex using multivariable log-linear regression, adjusting for clinical risk factors for stroke, and stratifying by warfarin use. We identified 394 ischemic stroke and peripheral embolic events during 15 494 person-years of follow-up off warfarin. After multivariable analysis, women had higher annual rates of thromboembolism off warfarin than did men (3.5% versus 1.8%; adjusted rate ratio [RR], 1.6; 95% CI, 1.3 to 1.9). There was no significant difference by sex in 30-day mortality after thromboembolism (23% for both). Warfarin use was associated with significantly lower adjusted thromboembolism rates for both women and men (RR, 0.4; 95% CI, 0.3 to 0.5; and RR, 0.6; 95% CI, 0.5 to 0.8, respectively), with similar annual rates of major hemorrhage (1.0% and 1.1%, respectively).

Conclusions— Women are at higher risk than men for AF-related thromboembolism off warfarin. Warfarin therapy appears be as effective in women, if not more so, than in men, with similar rates of major hemorrhage. Female sex is an independent risk factor for thromboembolism and should influence the decision to use anticoagulant therapy in persons with AF.

Key Words: anticoagulants • atrial fibrillation • risk factors • stroke • women

This article has been cited by other articles:

				M. L. Hansen, N. Gadsboll, G. H. Gislason, S. Z. Abildstrom, T. K. Schramm, F. Folke, J. Friberg, R. Sorensen, S. Rasmussen, H. E. Poulsen, et al. Atrial fibrillation pharmacotherapy after hospital discharge between 1995 and 2004: a shift towards beta-blockers Europace, April 1, 2008; 10(4): 395 - 402. [Abstract] [Full Text] [PDF]

				M. C. Fang, A. S. Go, Y. Chang, L. Borowsky, N. K. Pomernacki, D. E. Singer, and for the ATRIA Study Group Comparison of Risk Stratification Schemes to Predict Thromboembolism in People With Nonvalvular Atrial Fibrillation J. Am. Coll. Cardiol., February 26, 2008; 51(8): 810 - 815. [Abstract] [Full Text] [PDF]

				The Stroke Risk in Atrial Fibrillation Working Gro Independent predictors of stroke in patients with atrial fibrillation: A systematic review Neurology, August 7, 2007; 69(6): 546 - 554. [Abstract] [Full Text] [PDF]

				G. B. Forleo, C. Tondo, L. De Luca, A. D. Russo, M. Casella, V. De Sanctis, F. Clementi, R. L. Fagundes, R. Leo, F. Romeo, et al. Gender-related differences in catheter ablation of atrial fibrillation Europace, August 1, 2007; 9(8): 613 - 620. [Abstract] [Full Text] [PDF]

				J. Roquer, A. Ois, A. Rodriguez-Campello, M. Gomis, E. Munteis, J. Jimenez-Conde, E. Cuadrado-Godia, and J. E. Martinez-Rodriguez Atherosclerotic Burden and Early Mortality in Acute Ischemic Stroke Arch Neurol, May 1, 2007; 64(5): 699 - 704. [Abstract] [Full Text] [PDF]

				Writing Committee Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation: full text: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Europace, September 1, 2006; 8(9): 651 - 745. [Full Text] [PDF]

				V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): 854 - 906. [Full Text] [PDF]

				V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society J. Am. Coll. Cardiol., August 15, 2006; 48(4): e149 - e246. [Full Text] [PDF]

				V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation, August 15, 2006; 114(7): e257 - e354. [Full Text] [PDF]

				V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, J. E. Lowe, et al. ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation--Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients With Atrial Fibrillation): Developed in Collaboration With the European Heart Rhythm Association and the Heart Rhythm Society Circulation, August 15, 2006; 114(7): 700 - 752. [Full Text] [PDF]

				Authors/Task Force Members, V. Fuster, L. E. Ryden, D. S. Cannom, H. J. Crijns, A. B. Curtis, K. A. Ellenbogen, J. L. Halperin, J.-Y. Le Heuzey, G. N. Kay, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation executive summary: A report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Revise the 2001 Guidelines for the Management of Patients with Atrial Fibrillation) Developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society Eur. Heart J., August 2, 2006; 27(16): 1979 - 2030. [Full Text] [PDF]

				M. Gomberg-Maitland, N. K. Wenger, J. Feyzi, M. Lengyel, A. S. Volgman, P. Petersen, L. Frison, and J. L. Halperin Anticoagulation in women with non-valvular atrial fibrillation in the stroke prevention using an oral thrombin inhibitor (SPORTIF) trials Eur. Heart J., August 2, 2006; 27(16): 1947 - 1953. [Abstract] [Full Text] [PDF]

				G. Y.H. Lip, T. Watson, and E. Shantsila Anticoagulation for stroke prevention in atrial fibrillation: is gender important? Eur. Heart J., August 2, 2006; 27(16): 1893 - 1894. [Full Text] [PDF]

				L. Friberg, N. Hammar, M. Ringh, H. Pettersson, and M. Rosenqvist Stroke prophylaxis in atrial fibrillation: who gets it and who does not?: Report from the Stockholm Cohort-study on Atrial Fibrillation (SCAF-study) Eur. Heart J., August 2, 2006; 27(16): 1954 - 1964. [Abstract] [Full Text] [PDF]

				M. Stramba-Badiale, K. M. Fox, S. G. Priori, P. Collins, C. Daly, I. Graham, B. Jonsson, K. Schenck-Gustafsson, and M. Tendera Cardiovascular diseases in women: a statement from the policy conference of the European Society of Cardiology Eur. Heart J., April 2, 2006; 27(8): 994 - 1005. [Abstract] [Full Text] [PDF]