(Stroke. 1999;30:1223-1229.)
© 1999 American Heart Association, Inc.
Original Contributions |
Factors Associated With Ischemic Stroke During Aspirin Therapy in Atrial Fibrillation
Analysis of 2012 Participants in the SPAF I–III Clinical Trials
From the University of Texas Health Science Center, San Antonio (R.G.H.); Statistics and Epidemiology Research Corporation, Seattle, Wash (L.A.P., R. McB.); LeBauer Cardiology Associates, Greensboro, NC (R.M.R.); and Hennepin County Medical Center, Minneapolis, Minn (R.W.A.), on behalf of the Stroke Prevention in Atrial Fibrillation (SPAF) Investigators.
Correspondence to Robert G. Hart, MD, Department of Medicine (Neurology), University of Texas Health Science Center, 7703 Floyd Curl Dr, San Antonio, TX 78284. E-mail HartR{at}uthscsa.edu
Background and Purpose—Nonvalvular atrial fibrillation (AF) is a strong, independent risk factor for stroke, but the absolute rate of stroke varies widely among AF patients, importantly influencing the potential benefit of antithrombotic prophylaxis. We explore factors associated with ischemic stroke in AF patients taking aspirin.
Methods—We performed multivariate logistic regression analysis of 2012 participants given aspirin alone or in combination with low, inefficacious doses of warfarin in the Stroke Prevention in Atrial Fibrillation I–III trials followed for a mean of 2.0 years, during which 130 ischemic strokes were observed.
Results—Age (relative risk [RR]=1.8 per decade,
P<0.001), female sex (RR=1.6,
P=0.01), history of hypertension (RR=2.0,
P<0.001), systolic blood pressure >160
mm Hg (RR=2.3, P<0.001), and prior stroke or transient
ischemic attack (RR=2.9, P<0.001) were
independently associated with increased stroke risk. Regular
consumption of 
14 alcohol-containing drinks per week was associated
with reduced stroke risk (adjusted RR=0.4, P=0.04).
Among SPAF III participants, estrogen hormone replacement therapy was
associated with a higher risk of ischemic stroke (adjusted
RR=3.2, P=0.007). With the use of these variables, a
risk stratification scheme for primary prevention separated
participants into those with high (7.1%/y, 22% of the cohort),
moderate (2.6%/y, 37% of the cohort), and low (0.9%/y, 41% of the
cohort) rates of stroke. Ischemic strokes in low-risk
participants were less often disabling (P<0.001).
Conclusions—Patients with AF who have high and low rates of stroke during treatment with aspirin can be identified. However, validation of our risk stratification scheme is necessary before it can be applied with confidence to clinical management. Postmenopausal estrogen replacement therapy and moderate alcohol consumption may additionally modify the risk of stroke in AF, but these findings require confirmation.
Key Words: atrial fibrillation • cerebral embolism • estrogens • risk factors • stroke prevention
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D. S.G. Conway, J. Heeringa, D. A.M. Van Der Kuip, B. S.P. Chin, A. Hofman, J. C.M. Witteman, and G. Y.H. Lip Atrial Fibrillation and the Prothrombotic State in the Elderly: The Rotterdam Study Stroke, February 1, 2003; 34(2): 413 - 417. [Abstract] [Full Text] [PDF]
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N. Radford, T. Church, F. E. Speizer, B. E. Pearson Murphy, S. R. Davis, H. G. Burger, W. H. Goodson III, H. R. Franke, I. Lev, A. Lahad, et al. Risks of Postmenopausal Hormone Replacement JAMA, December 11, 2002; 288(22): 2819 - 2824. [Full Text] [PDF]
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 I. C. Van Gelder, V. E. Hagens, H. A. Bosker, J. H. Kingma, O. Kamp, T. Kingma, S. A. Said, J. I. Darmanata, A. J.M. Timmermans, J. G.P. Tijssen, et al. A Comparison of Rate Control and Rhythm Control in Patients with Recurrent Persistent Atrial Fibrillation N. Engl. J. Med., December 5, 2002; 347(23): 1834 - 1840. [Abstract] [Full Text] [PDF]
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R. H. Falk Management of Atrial Fibrillation -- Radical Reform or Modest Modification? N. Engl. J. Med., December 5, 2002; 347(23): 1883 - 1884. [Full Text] [PDF]
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M. S. Mouradian, S. R. Majumdar, A. Senthilselvan, K. Khan, and A. Shuaib How Well Are Hypertension, Hyperlipidemia, Diabetes, and Smoking Managed After a Stroke or Transient Ischemic Attack? Stroke, June 1, 2002; 33(6): 1656 - 1659. [Abstract] [Full Text] [PDF]
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B. G. Angeja, M. G. Shlipak, A. S. Go, S. C. Johnston, P. D. Frederick, J. G. Canto, H. V. Barron, D. Grady, and for the National Registry of Myocardial Infarction Hormone therapy and the risk of stroke after acute myocardial infarction in postmenopausal women J. Am. Coll. Cardiol., November 1, 2001; 38(5): 1297 - 1301. [Abstract] [Full Text] [PDF]
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V. Fuster, L. E. Ryden, R. W. Asinger, D. S. Cannom, H. J. Crijns, R. L. Frye, J. L. Halperin, G. N. Kay, W. W. Klein, S. Levy, et al. ACC/AHA/ESC 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 and Policy Conferences (Committee to Develop Guidelines for the Management of Patients With Atrial Fibrillation) Developed in Collaboration With the North American Society of Pacing and Electrophysiology Circulation, October 23, 2001; 104(17): 2118 - 2150. [Full Text] [PDF]
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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 and Policy Conferences (Committee to develop guidelines for the management of patients with atrial fibrillation) developed in collaboration with the North American Society of Pacing and Electrophysiology Eur. Heart J., October 2, 2001; 22(20): 1852 - 1923. [PDF]
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A. J. Makin, D. S. G. Conway, G. Y. H. Lip, L. Frost, S. P. Johnsen, G. Engholm, E. Henneberg, and S. Husted Systemic Thromboembolism in Atrial Fibrillation Arch Intern Med, August 13, 2001; 161(15): 1920 - 1924. [Full Text] [PDF]
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B. F. Gage, A. D. Waterman, W. Shannon, M. Boechler, M. W. Rich, and M. J. Radford Validation of Clinical Classification Schemes for Predicting Stroke: Results From the National Registry of Atrial Fibrillation JAMA, June 13, 2001; 285(22): 2864 - 2870. [Abstract] [Full Text] [PDF]
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R. G. Hart and J. L. Halperin Atrial Fibrillation and Stroke : Concepts and Controversies Stroke, March 1, 2001; 32(3): 803 - 808. [Full Text] [PDF]
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J. A. Simon, J. Hsia, J. A. Cauley, C. Richards, F. Harris, J. Fong, E. Barrett-Connor, and S. B. Hulley Postmenopausal Hormone Therapy and Risk of Stroke : The Heart and Estrogen-progestin Replacement Study (HERS) Circulation, February 6, 2001; 103(5): 638 - 642. [Abstract] [Full Text] [PDF]
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G. W. Albers, J. E. Dalen, A. Laupacis, W. J. Manning, P. Petersen, and D. E. Singer Antithrombotic Therapy in Atrial Fibrillation Chest, January 1, 2001; 119(1_suppl): 194S - 206S. [Full Text] [PDF]
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R. G. Hart Anticoagulation therapy for patients with atrial fibrillation Can. Med. Assoc. J., October 1, 2000; 163(8): 956 - 957. [Full Text] [PDF]
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A. S. Go, E. M. Hylek, K. A. Phillips, L. H. Borowsky, L. E. Henault, Y. Chang, J. V. Selby, and D. E. Singer Implications of Stroke Risk Criteria on the Anticoagulation Decision in Nonvalvular Atrial Fibrillation : The Anticoagulation and Risk Factors In Atrial Fibrillation (ATRIA) Study Circulation, July 4, 2000; 102(1): 11 - 13. [Abstract] [Full Text] [PDF]
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S. Stern, D. Altkorn, and W. Levinson Anticoagulation for Chronic Atrial Fibrillation JAMA, June 14, 2000; 283(22): 2901 - 2903. [Full Text] [PDF]
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S. MacMahon Blood Pressure and the Risk of Cardiovascular Disease N. Engl. J. Med., January 6, 2000; 342(1): 49 - 52. [Full Text]
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R. G. Hart, L. A. Pearce, R. M. Rothbart, J. H. McAnulty, R. W. Asinger, J. L. Halperin, and for the Stroke Prevention in Atrial Fibrillation I Stroke with intermittent atrial fibrillation: incidence and predictors during aspirin therapy J. Am. Coll. Cardiol., January 1, 2000; 35(1): 183 - 187. [Abstract] [Full Text] [PDF]
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W. M. Feinberg, L. A. Pearce, R. G. Hart, M. Cushman, E. S. Cornell, G. Y.H. Lip, and E. G. Bovill 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, December 1, 1999; 30(12): 2547 - 2553. [Abstract] [Full Text] [PDF]
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R. G. Hart and J. L. Halperin Atrial Fibrillation and Thromboembolism: A Decade of Progress in Stroke Prevention Ann Intern Med, November 2, 1999; 131(9): 688 - 695. [Abstract] [Full Text] [PDF]
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R. G HART Warfarin in atrial fibrillation: underused in the elderly, often inappropriately used in the young Heart, November 1, 1999; 82(5): 539 - 540. [Full Text]
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R. G. Hart, O. Benavente, R. McBride, and L. A. Pearce Antithrombotic Therapy To Prevent Stroke in Patients with Atrial Fibrillation: A Meta-Analysis Ann Intern Med, October 5, 1999; 131(7): 492 - 501. [Abstract] [Full Text] [PDF]
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J. H. Lichtman, H. M. Krumholz, Y. Wang, M. J. Radford, and L. M. Brass Risk and Predictors of Stroke After Myocardial Infarction Among the Elderly: Results From the Cooperative Cardiovascular Project Circulation, March 5, 2002; 105(9): 1082 - 1087. [Abstract] [Full Text] [PDF]
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