Atrial fibrillation, even in the absence of rheumatic valvular disease, predisposes patients to embolic complications, but the role of antithrombotic therapy in the prevention of such complications has not been fully clarified. We therefore performed a randomized, placebo-controlled trial to evaluate warfarin and aspirin individually as prophylaxis against ischemic stroke and systemic embolism (the primary events) in such patients. Patients eligible to receive warfarin (group 1) were assigned to warfarin (open label), aspirin (325 mg per day), or placebo (aspirin and placebo were given in a doubleblind fashion). Those who were not eligible for warfarin (group 2) received either aspirin or placebo in a double-blind fashion. The placebo arm of group 1 was recently terminated, when evidence emerged that each active agent was superior to placebo. In this paper we report preliminary data on active therapy (with either warfarin or aspirin) as compared with placebo in group 1, and on aspirin as compared with placebo in groups 1 and 2 combined. By November 1989, 1244 patients had been followed for a mean of 1.13 years. The event rates were 1.6 percent per year in the 393 patients who made up the two active treatment arms (warfarin and aspirin) of group 1, and 8.3 percent per year in the 195 patients who made up the placebo arm (P less than 0.00005) (risk reduction, 81 percent; 95 percent confidence interval, 56 to 91). In all 517 patients given aspirin, the rate of primary events (3.2 percent per year) was lower than that in the 528 patients given placebo (6.3 percent per year; P = 0.014) (risk reduction, 49 percent; 95 percent confidence interval, 15 to 69). However, we were unable to show a benefit of aspirin in patients over 75 years of age. These preliminary data indicate that antithrombotic therapy with warfarin or aspirin is effective in the short term in reducing the risk of stroke and systemic embolism in patients with atrial fibrillation due to causes other than rheumatic valvular disease. The relative benefits of aspirin and warfarin remain unclear, and the trial is continuing in order to address this issue.
This article has been cited by other articles:
2006 WRITING COMMITTEE MEMBERS, , Bonow, R. O., Carabello, B. A., Chatterjee, K., de Leon, A. C. Jr, Faxon, D. P., Freed, M. D., Gaasch, W. H., Lytle, B. W., Nishimura, R. A., O'Gara, P. T., O'Rourke, R. A., Otto, C. M., Shah, P. M., Shanewise, J. S.
(2008). 2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation
118: e523-e661
[Full Text]
Bonow, R. O., Carabello, B. A., Chatterjee, K., de Leon, A. C. Jr, Faxon, D. P., Freed, M. D., Gaasch, W. H., Lytle, B. W., Nishimura, R. A., O'Gara, P. T., O'Rourke, R. A., Otto, C. M., Shah, P. M., Shanewise, J. S., Nishimura, R. A., Carabello, B. A., Faxon, D. P., Freed, M. D., Lytle, B. W., O'Gara, P. T., O'Rourke, R. A., Shah, P. M.
(2008). 2008 Focused Update Incorporated Into the ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol
52: e1-e142
[Full Text]
Patrono, C., Baigent, C., Hirsh, J., Roth, G.
(2008). Antiplatelet Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 199S-233S
[Abstract][Full Text]
Schulman, S., Beyth, R. J., Kearon, C., Levine, M. N.
(2008). Hemorrhagic Complications of Anticoagulant and Thrombolytic Treatment: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 257S-298S
[Abstract][Full Text]
Salem, D. N., O'Gara, P. T., Madias, C., Pauker, S. G.
(2008). Valvular and Structural Heart Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest
133: 593S-629S
[Abstract][Full Text]
Holbrook, A., Labiris, R., Goldsmith, C. H., Ota, K., Harb, S., Sebaldt, R. J.
(2007). Influence of decision aids on patient preferences for anticoagulant therapy: a randomized trial. CMAJ
176: 1583-1587
[Abstract][Full Text]
Bonow, R. O., Carabello, B. A., Chatterjee, K., de Leon, A. C. Jr, Faxon, D. P., Freed, M. D., Gaasch, W. H., Lytle, B. W., Nishimura, R. A., O'Gara, P. T., O'Rourke, R. A., Otto, C. M., Shah, P. M., Shanewise, J. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Faxon, D. P., Fuster, V., Halperin, J. L., Hiratzka, L. F., Hunt, S. A., Lytle, B. W., Nishimura, R., Page, R. L., Riegel, B.
(2006). ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Developed in Collaboration With the Society of Cardiovascular Anesthesiologists Endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol
48: e1-e148
[Full Text]
Bonow, R. O., Carabello, B. A., Chatterjee, K., de Leon, A. C. Jr, Faxon, D. P., Freed, M. D., Gaasch, W. H., Lytle, B. W., Nishimura, R. A., O'Gara, P. T., O'Rourke, R. A., Otto, C. M., Shah, P. M., Shanewise, J. S., Smith, S. C. Jr, Jacobs, A. K., Adams, C. D., Anderson, J. L., Antman, E. M., Faxon, D. P., Fuster, V., Halperin, J. L., Hiratzka, L. F., Hunt, S. A., Lytle, B. W., Nishimura, R., Page, R. L., Riegel, B.
(2006). ACC/AHA 2006 Practice Guidelines for the Management of Patients With Valvular Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease) Developed in Collaboration With the Society of Cardiovascular Anesthesiologists Endorsed by the Society for Cardiovascular Angiography and Interventions and the Society of Thoracic Surgeons. J Am Coll Cardiol
48: 598-675
[Full Text]
Patrono, C., Coller, B., FitzGerald, G. A., Hirsh, J., Roth, G.
(2004). Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 234S-264S
[Abstract][Full Text]
Levine, M. N., Raskob, G., Beyth, R. J., Kearon, C., Schulman, S.
(2004). Hemorrhagic Complications of Anticoagulant Treatment: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 287S-310S
[Abstract][Full Text]
Salem, D. N., Stein, P. D., Al-Ahmad, A., Bussey, H. I., Horstkotte, D., Miller, N., Pauker, S. G.
(2004). Antithrombotic Therapy in Valvular Heart Disease--Native and Prosthetic: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest
126: 457S-482S
[Abstract][Full Text]
Kasliwal, R. R, Mukesh, S., Manohar, G., Aggarwal, N., Bhatia, A.
(2003). Pharmacotherapy of Atrial Fibrillation. Asian Cardiovasc. Thorac. Ann.
11: 364-374
[Abstract][Full Text]
Hart, R. G., Halperin, J. L., Pearce, L. A., Anderson, D. C., Kronmal, R. A., McBride, R., Nasco, E., Sherman, D. G., Talbert, R. L., Marler, J. R., for the Stroke Prevention in Atrial Fibrillation I,
(2003). Lessons from the Stroke Prevention in Atrial Fibrillation Trials. ANN INTERN MED
138: 831-838
[Abstract][Full Text]
Aronow, W. S.
(2002). Management of the Older Person With Atrial Fibrillation. Journals of Gerontology Series A: Biological Sciences and Medical Sciences
57: M352-363
[Abstract][Full Text]
Man-Son-Hing, M., Laupacis, A.
(2002). Balancing the Risks of Stroke and Upper Gastrointestinal Tract Bleeding in Older Patients With Atrial Fibrillation. Arch Intern Med
162: 541-550
[Abstract][Full Text]
Corrado, G, Sgalambro, A, Mantero, A, Gentile, F, Gasparini, M, Bufalino, R, Morabito, A, Trocino, G, Schiavina, R, Mandorla, S, Mangia, R, Tovena, D, Savino, K, Jacopi, F, Pellegrino, E.M, Agostini, F, Centonze, G, Bovenzi, F, Caprino, E, Tadeo, G, Santarone, M
(2001). Thromboembolic risk in atrial flutter. The FLASIEC (FLutterAtrialeSocietaIaliana diEcografiaCardiovascolare) multicentre study. Eur Heart J
22: 1042-1051
[Abstract]
Butchart, E. G., Li, H.-H., Payne, N., Buchan, K., Grunkemeier, G. L.
(2001). Twenty years' experience with the Medtronic Hall valve. J. Thorac. Cardiovasc. Surg.
121: 1090-1100
[Abstract][Full Text]
Andraghetti, A., Scalese, M.
(2001). Safety and efficacy of low-energy cardioversion of 500 patients using two different techniques. Europace
3: 4-9
[Abstract]
Patrono, C., Coller, B., Dalen, J. E., FitzGerald, G. A., Fuster, V., Gent, M., Hirsh, J., Roth, G.
(2001). Platelet-Active Drugs : The Relationships Among Dose, Effectiveness, and Side Effects. Chest
119
: 39S-63S
[Full Text]
Levine, M. N., Raskob, G., Landefeld, S., Kearon, C.
(2001). Hemorrhagic Complications of Anticoagulant Treatment. Chest
119
: 108S-121S
[Full Text]
Salem, D. N., Hartnett Daudelin, D., Levine, H. J., Pauker, S. G., Eckman, M. H., Riff, J.
(2001). Antithrombotic Therapy in Valvular Heart Disease. Chest
119
: 207S-219S
[Full Text]
Tegos, T. J., Kalodiki, E., Nicolaides, A. N.
(2000). Stroke: Management and Rehabilitation: Part III of III. ANGIOLOGY
51: 977-984
[Abstract]
Tramèr, M. R
(2000). Aspirin, like all other drugs, is a poison. BMJ
321: 1170-1171
[Full Text]
Furlan, A. J.
(2000). CVA: Reducing the Risk of a Confused Vascular Analysis : The Feinberg Lecture. Stroke
31: 1451-1456
[Full Text]
Handa, N., Schaff, H. V., Morris, J. J., Anderson, B. J., Kopecky, S. L., Enriquez-Sarano, M.
(1999). OUTCOME OF VALVE REPAIR AND THE COX MAZE PROCEDURE FOR MITRAL REGURGITATION AND ASSOCIATED ATRIAL FIBRILLATION. J. Thorac. Cardiovasc. Surg.
118: 628-635
[Abstract][Full Text]
Jamieson, W.R. E., Miyagishima, R. T., Grunkemeier, G. L., Germann, E., Henderson, C., Fradet, G. J., Burr, L. H., Lichtenstein, S. V.
(1999). Bileaflet mechanical prostheses performance in mitral position. Eur. J. Cardiothorac. Surg.
15: 786-794
[Abstract][Full Text]
Man-Son-Hing, M., Nichol, G., Lau, A., Laupacis, A.
(1999). Choosing Antithrombotic Therapy for Elderly Patients With Atrial Fibrillation Who Are at Risk for Falls. Arch Intern Med
159: 677-685
[Abstract][Full Text]
Furberg, C. D.
(1999). Natural Statins and Stroke Risk. Circulation
99: 185-188
[Full Text]
Eckman, M. H., Falk, R. H., Pauker, S. G.
(1998). Cost-effectiveness of Therapies for Patients With Nonvalvular Atrial Fibrillation. Arch Intern Med
158: 1669-1677
[Abstract][Full Text]
Gage, B. F., Cardinalli, A. B., Owens, D. K.
(1998). Cost-Effectiveness of Preference-Based Antithrombotic Therapy for Patients With Nonvalvular Atrial Fibrillation. Stroke
29: 1083-1091
[Abstract][Full Text]
Kalra, L., Perez, I., Melbourn, A.
(1998). Stroke Risk Management : Changes in Mainstream Practice. Stroke
29: 53-57
[Abstract][Full Text]
Sato, Y., Honda, Y., Kunoh, H., Oizumi, K.
(1997). Long-term Oral Anticoagulation Reduces Bone Mass in Patients with Previous Hemispheric Infarction and Nonrheumatic Atrial Fibrillation. Stroke
28: 2390-2394
[Abstract][Full Text]
Manolio, T. A., Kronmal, R. A., Burke, G. L., O'Leary, D. H., Price, T. R.
(1996). Short-term Predictors of Incident Stroke in Older Adults: The Cardiovascular Health Study. Stroke
27: 1479-1486
[Abstract][Full Text]
Mathew, J. P., Parks, R., Savino, J. S., Friedman, A. S., Koch, C., Mangano, D. T., Browner, W. S.
(1996). Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery: Predictors, Outcomes, and Resource Utilization. JAMA
276: 300-306
[Abstract]
Hirsh, J., Hoak, J.
(1996). Management of Deep Vein Thrombosis and Pulmonary Embolism : A Statement for Healthcare Professionals From the Council on Thrombosis (in Consultation With the Council on Cardiovascular Radiology), American Heart Association. Circulation
93: 2212-2245
[Full Text]
Martinez-Riera, A., Santolaria-Fernandez, F., Gonzalez-Reimers, E., Perry, I. J., Gilbert, R.E., Jerums, G., Cooper, M.E., Bronner, L. L., Kanter, D. S., Manson, J. E.
(1996). Primary Prevention of Stroke. NEJM
334: 1138-1139
[Full Text]
Gage, B. F., Cardinalli, A. B., Albers, G. W., Owens, D. K.
(1995). Cost-effectiveness of Warfarin and Aspirin for Prophylaxis of Stroke in Patients With Nonvalvular Atrial Fibrillation. JAMA
274: 1839-1845
[Abstract]
Lackner, T. E., Battis, G. N.
(1995). Use of Warfarin for Nonvalvular Atrial Fibrillation in Nursing Home Patients. Arch Fam Med
4: 1017-1026
[Abstract]
Zarembski, D. G., Nolan, P. E. Jr, Slack, M. K., Caruso, A. C.
(1995). Treatment of Resistant Atrial Fibrillation: A Meta-analysis Comparing Amiodarone and Flecainide. Arch Intern Med
155: 1885-1891
[Abstract]
Kinch, J. W., Davidoff, R.
(1995). Prevention of Embolic Events After Cardioversion of Atrial Fibrillation: Current and Evolving Strategies. Arch Intern Med
155: 1353-1360
[Abstract]
The European Atrial Fibrillation Trial Study Group,
(1995). Optimal Oral Anticoagulant Therapy in Patients with Nonrheumatic Atrial Fibrillation and Recent Cerebral Ischemia. NEJM
333: 5-10
[Abstract][Full Text]
Gorelick, P. B.
(1995). Stroke Prevention. Arch Neurol
52: 347-355
[Abstract]
Bankl, H. C., Radaszkiewicz, T., Klappacher, G. W., Glogar, D., Sperr, W. R., Großschmidt, K., Bankl, H., Lechner, K., Valent, P.
(1995). Increase and Redistribution of Cardiac Mast Cells in Auricular Thrombosis : Possible Role of kit Ligand. Circulation
91: 275-283
[Abstract][Full Text]
Vial, J. H., Narkowicz, C.
(1995). Comparison of Cyclooxygenase Inhibition with Two Different Doses of Enteric Coated Aspirin in Normal Young and Elderly Subjects and Elderly with Cerebrovascular Disease. CLIN APPL THROMB HEMOST
1: 55-61
[Abstract]
Antiplatelet Trialists,
(1994). Collaborative overview of randomised trials of antiplatelet therapy Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. BMJ
308: 81-106
[Abstract][Full Text]
Howard, J. E., Poller, L., Barnes, D. J., Ezekowitz, M. D., James, K. E.
(1993). Warfarin in the Prevention of Stroke Associated with Nonrheumatic Atrial Fibrillation. NEJM
328: 1041-1043
[Full Text]
Daniel, W. G.
(1993). Should Transesophageal Echocardiography Be Used to Guide Cardioversion?. NEJM
328: 803-804
[Full Text]
Naglie, I. G., Detsky, A. S.
(1992). Treatment of Chronic Nonvalvular Atrial Fibrillation in the Elderly: A Decision Analysis. Med Decis Making
12: 239-249
[Abstract]
Alves, L. E., Rose, E. P.
(1992). A Proposed Trial of Amiodarone for Atrial Fibrillation. ANN INTERN MED
117: 972-973
[Abstract]
Pagliaro, L., D'Amico, G., Sorensen, T. I. A., Lebrec, D., Burroughs, A. K., Morabito, A., Tine, F., Politi, F., Traina, M.
(1992). Prevention of First Bleeding in Cirrhosis: A Meta-Analysis of Randomized Trials of Nonsurgical Treatment. ANN INTERN MED
117: 59-70
[Abstract]
Middlekauff, H. R., Wiener, I., Saxon, L. A., Stevenson, W. G.
(1992). Low-Dose Amiodarone for Atrial Fibrillation: Time for a Prospective Study?. ANN INTERN MED
116: 1017-1020
[Abstract]
Landefeld, C. S., Anderson, P. A.
(1992). Guideline-based Consultation To Prevent Anticoagulant-related Bleeding: A Randomized, Controlled Trial in a Teaching Hospital. ANN INTERN MED
116: 829-837
[Abstract]
McCurdy, S. A., White, R. H.
(1992). Accuracy and Precision of a Portable Anticoagulation Monitor in a Clinical Setting. Arch Intern Med
152: 589-592
[Abstract]
Rothrock, J. F., Hart, R. G.
(1991). Antithrombotic Therapy in Cerebrovascular Disease. ANN INTERN MED
115: 885-895
[Abstract]
Laupacis, A., Connolly, S. J., Gent, M., Roberts, R. S., Cairns, J., Joyner, C., CAFA Study Group,
(1991). How Should Results from Completed Studies Influence Ongoing Clinical Trials? The CAFA Study Experience. ANN INTERN MED
115: 818-822
[Abstract]
Hirsh, J.
(1991). Influence of Low-Intensity Warfarin Treatment on Patients' Perceptions of Quality of Life. Arch Intern Med
151: 1921-1922
[Abstract]
Dalen, J. E.
(1991). Atrial Fibrillation and Embolic Stroke. Arch Intern Med
151: 1922-1924
[Abstract]
Lancaster, T. R., Singer, D. E., Sheehan, M. A., Oertel, L. B., Maraventano, S. W., Hughes, R. A., Kistler, J. P.
(1991). The Impact of Long-term Warfarin Therapy on Quality of Life: Evidence From a Randomized Trial. Arch Intern Med
151: 1944-1949
[Abstract]
Kutner, M., Nixon, G., Silverstone, F.
(1991). Physicians' Attitudes Toward Oral Anticoagulants and Antiplatelet Agents for Stroke Prevention in Elderly Patients With Atrial Fibrillation. Arch Intern Med
151: 1950-1953
[Abstract]
Halperin, J. L
(1991). Prevention of embolism in atrial fibrillation. Vasc Med
2: 111-119
The Asymptomatic Cervical Bruit Study Group,
(1991). Natural History and Effectiveness of Aspirin in Asymptomatic Patients With Cervical Bruits. Arch Neurol
48: 683-686
[Abstract]
Gore, J. M., Dalen, J. E.
(1991). Cardiovascular Disease. JAMA
265: 3105-3107
[Abstract]
Dalen, J. E.
(1991). An Apple a Day or an Aspirin a Day?. Arch Intern Med
151: 1066-1069
[Abstract]
Ridker, P. M., Manson, J. E., Gaziano, J. M., Buring, J. E., Hennekens, C. H.
(1991). Low-Dose Aspirin Therapy for Chronic Stable Angina: A Randomized, Placebo-Controlled Clinical Trial. ANN INTERN MED
114: 835-839
[Abstract]
Grotta, J. C
(1991). Prevention and management of stroke. Vasc Med
2: 3-17
(1990). WARFARIN AND ASPIRIN REDUCE EMBOLIC STROKE IN NON- RHEUMATIC ATRIAL FIBRILLATION. JWatch General
1990: 1-1
[Full Text]
Previous
