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Antiarrhythmic Prophylaxis vs Warfarin Anticoagulation to Prevent Thromboembolic Events Among Patients With Atrial Fibrillation: A Decision Analysis

Antiarrhythmic Prophylaxis vs Warfarin Anticoagulation to Prevent Thromboembolic Events Among... Abstract Background: Patients with atrial fibrillation compared with those with sinus rhythm are at increased risk for thromboembolism, often mandating therapy directed at thromboembolism prevention. However, the safest, most efficacious strategy to prevent thromboembolism associated with atrial fibrillation is unknown. We developed a decision analysis to compare the risks and benefits of two common clinical strategies to prevent thromboembolism in the patient with atrial fibrillation: (1) sinus rhythm maintenance with quinidine sulfate or with amiodarone hydrochloride after cardioversion and (2) long-term anticoagulation with warfarin sodium. Methods: A search was conducted of the Englishlanguage MEDLINE databases of the National Library of Medicine dated 1966 through December 1992. The search was conducted by intersecting "quinidine," "warfarin," or "amiodarone" with "atrial fibrillation." Six of 249 articles concerning quinidine and five of 20 articles concerning warfarin were judged by multiple reviewers to meet predetermined inclusion and exclusion criteria. To our knowledge, no randomized, placebo-controlled trials of amiodarone therapy for atrial fibrillation have been published. Five of 112 identified articles concerning amiodarone involved nonrandomized trials that met the remaining selection criteria and were included in this analysis. Results: Thromboembolic events and fatal nonthromboembolic adverse events during the course of therapy (defined as fatal proarrhythmia, fatal hemorrhage, and fatal noncardiac toxic effects) were considered to have equivalent weight. The total risk during therapy, defined as thromboembolic and fatal nonthromboembolic adverse events during the course of therapy, was evaluated over a range of baseline thromboembolism risks, from 1% to 20% per patient-year. Quinidine therapy compared with no therapy was associated with increased total risk, unless baseline thromboembolism risk exceeded 11% per patient-year. Total risk during warfarin therapy was less than total risk during quinidine therapy for the entire range of baseline thromboembolism risks, from 1% to 20% per patient-year. Total risk during warfarin or amiodarone therapy was similar and less than that with no therapy for the entire range of baseline risks. Conclusions: Based on data from randomized, controlled trials of quinidine and warfarin, warfarin therapy appears to be the safest strategy for thromboembolism prevention in the patient with atrial fibrillation. The role of low-dose amiodarone therapy appears promising and warrants further study in randomized, controlled trials.(Arch Intern Med. 1995;155:913-920) References 1. Cairns JA, Connolly SJ. Nonrheumatic atrial fibrillation: risk of stroke and role of antithrombotic therapy. Circulation . 1991;84:469-481.Crossref 2. Wolf PA, Dawber TR, Thomas HE, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham Study. Neurology . 1978;28:973-977.Crossref 3. Boissel JP, Wolf E, Gillet J, et al. Controlled trial of a long-acting quinidine for maintenance of sinus rhythm after conversion of sustained atrial fibrillation. Eur Heart J . 1981;2:49-55. 4. Bryne-Quinn E, Wing AJ. Maintenance of sinus rhythm after DC reversion of atrial fibrillation: a double-blind controlled trial of quinidine bisulphate. Br Heart J . 1970;32:370-376.Crossref 5. Härtel G, Louhija A, Konttinen A, Halonen Pl. Value of quinidine in maintenance of sinus rhythm after electric conversion of atrial fibrillation. Br Heart J . 1970;32:57-60.Crossref 6. Hillestad L, Bjerkelund C, Dale J, Maltau J, Storstein O. Quinidine in maintenance of sinus rhythm after electroconversion of chronic atrial fibrillation: a controlled clinical study. Br Heart J . 1971;33:518-521.Crossref 7. Lloyd EA, Gersh BJ, Forman R. The efficacy of quinidine and disopyramide in the maintenance of sinus rhythm after electroconversion from atrial fibrillation: a double-blind study comparing quinidine, disopyramide and placebo. S Afr Med J . 1984;65;367-369. 8. Södermark T, Jonsson B, Olsson A, et al. Effect of quinidine on maintaining sinus rhythm after conversion of atrial fibrillation or flutter: a multicentre study from Stockholm. Br Heart J . 1975;37:486-492.Crossref 9. Antman EM, Beamer AD, Cantillon C, McGowan N, Friedman PL. Therapy of refractory symptomatic atrial fibrillation and atrial flutter: a staged care approach with new antiarrhythmic drugs. J Am Coll Cardiol . 1990;15:698-707.Crossref 10. Juul-Moller S, Edvardsson N, Rehnqvist-Ahlberg N. Sotolol versus quinidine for the maintenance of sinus rhythm after direct current conversion of atrial fibrillation. Circulation . 1990;82:1932-1939.Crossref 11. Coplen SE, Antman EM, Berlin JA. Hewitt P, Chalmers TC. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion: a meta-analysis of randomized control trials. Circulation . 1990;82:1106-1116.Crossref 12. Peterson P, Godtfredsen J, Boysen G, Anderson ED, Anderson B. Placebocontrolled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK Study. Lancet . 1989;1:175-178.Crossref 13. Stroke Prevention Atrial Fibrillation (SPAF) Investigators. Stroke prevention in atrial fibrillation study. Circulation . 1991;84:527-539.Crossref 14. Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med . 1990;323:1505-1511.Crossref 15. Canadian Atrial Fibrillation Anticoagulation (CAFA) Investigators. Canadian Atrial Fibrillation (CAFA) Study. J Am Coll Cardiol . 1991;18:349-355.Crossref 16. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation (SPINAF) Investigators. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. N Engl J Med . 1992;327:1406-1412.Crossref 17. Stroke Prevention in Atrial Fibrillation Investigators. Predictors of thromboembolism in atrial fibrillation, I: clinical features of patients at risk. Ann Intern Med . 1992;116:1-5.Crossref 18. Stroke Prevention in Atrial Fibrillation Investigators. Predictors of thromboembolism in atrial fibrillation, II: echocardiographic features of patients at risk. Ann Intern Med . 1992;116:6-12.Crossref 19. Kopecky SL, Gersh BJ, McGoon MD, et al. The natural history of lone atrial fibrillation. N Engl J Med . 1987;317:669-674.Crossref 20. Horowitz LN, Spielman SR, Greenspan AM, et al. Use of amiodarone in the treatment of persistent and paroxysmal atrial fibrillation resistant to quinidine therapy. J Am Coll Cardiol . 1985;6:1402-1407.Crossref 21. Gold RL, Haffajee Cl, Charos G, Sloan K, Baker S, Alpert JS. Amiodarone for refractory atrial fibrillation. Am J Cardiol . 1986;57:124-127.Crossref 22. Gosselink ATM, Crijns HJGM, Van Gelder IC, Hillige H, Wiesfeld ACP, Lie Kl. Low-dose amiodarone for maintenance of sinus rhythm after cardioversion of atrial fibrillation or flutter. JAMA . 1992;267:3289-3293.Crossref 23. Blevins RD, Kerin NZ, Benaderet D, et al. Amiodarone in the management of refractory atrial fibrillation. Arch Intern Med . 1987;147:1401-1404.Crossref 24. Brodsky MA, Allen BJ, Waler CJ, Casey TP, Luckett CR, Henry WL. Amiodarone for maintenance of sinus rhythm after conversion of atrial fibrillation in the setting of a dilated left atrium. Am J Cardiol . 1987;60:572-575.Crossref 25. Middlekauff HR, Wiener I, Saxon LA, Stevenson WG. Low-dose amiodarone for atrial fibrillation: time for a prospective study? Ann Intern Med . 1992;116: 1017-1020.Crossref 26. Middlekauff HR, Stevenson WG. Warfarin versus amiodarone for refractory atrial fibrillation: a decision analysis approach. Clin Res . 1993;41:77A. 27. Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet . 1994;343:687-691. 28. Martin A, Benbow LJ, Leach C, Bailey RJ. Comparison of amiodarone and disopyramide in the control of paroxysmal atrial fibrillation and atrial flutter (interim report). Br J Clin Pract Symp Suppl . 1986;44:52-60. 29. Kowey PR, Friehling TD, Marinchak RA, Sulpizi AM, Stohler JL. Safety and efficacy of amiodarone: the low-dose perspective. Chest . 1988:93:54-59.Crossref 30. Middlekauff HR, Stevenson WG, Saxon LA, Stevenson LW. Low-dose aminodarone for atrial fibrillation in advanced heart failure restores sinus rhythm and improves functional capacity. Circulation . 1992;86:I-808. 31. Disch DL, Greenberg ML, Holzberger PT, Malenka DJ, Birkmeyer JD. Managing chronic atrial fibrillation: a Markov decision analysis comparing warfarin, quinidine, and low-dose amiodarone. Ann Intern Med . 1994;120:449-457.Crossref 32. Chesebro JH, Fuster V, Halperin JL. Atrial fibrillation: risk marker for stroke. N Engl J Med . 1990;323:1556-1558.Crossref 33. Flaker GC, Blackshear JL, McBride R, Kronmal RA, Halperin JL, Hart RG. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. J Am Coll Cardiol . 1992;20:527-532.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

Antiarrhythmic Prophylaxis vs Warfarin Anticoagulation to Prevent Thromboembolic Events Among Patients With Atrial Fibrillation: A Decision Analysis

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Publisher
American Medical Association
Copyright
Copyright © 1995 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinte.1995.00430090044006
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Abstract

Abstract Background: Patients with atrial fibrillation compared with those with sinus rhythm are at increased risk for thromboembolism, often mandating therapy directed at thromboembolism prevention. However, the safest, most efficacious strategy to prevent thromboembolism associated with atrial fibrillation is unknown. We developed a decision analysis to compare the risks and benefits of two common clinical strategies to prevent thromboembolism in the patient with atrial fibrillation: (1) sinus rhythm maintenance with quinidine sulfate or with amiodarone hydrochloride after cardioversion and (2) long-term anticoagulation with warfarin sodium. Methods: A search was conducted of the Englishlanguage MEDLINE databases of the National Library of Medicine dated 1966 through December 1992. The search was conducted by intersecting "quinidine," "warfarin," or "amiodarone" with "atrial fibrillation." Six of 249 articles concerning quinidine and five of 20 articles concerning warfarin were judged by multiple reviewers to meet predetermined inclusion and exclusion criteria. To our knowledge, no randomized, placebo-controlled trials of amiodarone therapy for atrial fibrillation have been published. Five of 112 identified articles concerning amiodarone involved nonrandomized trials that met the remaining selection criteria and were included in this analysis. Results: Thromboembolic events and fatal nonthromboembolic adverse events during the course of therapy (defined as fatal proarrhythmia, fatal hemorrhage, and fatal noncardiac toxic effects) were considered to have equivalent weight. The total risk during therapy, defined as thromboembolic and fatal nonthromboembolic adverse events during the course of therapy, was evaluated over a range of baseline thromboembolism risks, from 1% to 20% per patient-year. Quinidine therapy compared with no therapy was associated with increased total risk, unless baseline thromboembolism risk exceeded 11% per patient-year. Total risk during warfarin therapy was less than total risk during quinidine therapy for the entire range of baseline thromboembolism risks, from 1% to 20% per patient-year. Total risk during warfarin or amiodarone therapy was similar and less than that with no therapy for the entire range of baseline risks. Conclusions: Based on data from randomized, controlled trials of quinidine and warfarin, warfarin therapy appears to be the safest strategy for thromboembolism prevention in the patient with atrial fibrillation. The role of low-dose amiodarone therapy appears promising and warrants further study in randomized, controlled trials.(Arch Intern Med. 1995;155:913-920) References 1. Cairns JA, Connolly SJ. Nonrheumatic atrial fibrillation: risk of stroke and role of antithrombotic therapy. Circulation . 1991;84:469-481.Crossref 2. Wolf PA, Dawber TR, Thomas HE, Kannel WB. Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham Study. Neurology . 1978;28:973-977.Crossref 3. Boissel JP, Wolf E, Gillet J, et al. Controlled trial of a long-acting quinidine for maintenance of sinus rhythm after conversion of sustained atrial fibrillation. Eur Heart J . 1981;2:49-55. 4. Bryne-Quinn E, Wing AJ. Maintenance of sinus rhythm after DC reversion of atrial fibrillation: a double-blind controlled trial of quinidine bisulphate. Br Heart J . 1970;32:370-376.Crossref 5. Härtel G, Louhija A, Konttinen A, Halonen Pl. Value of quinidine in maintenance of sinus rhythm after electric conversion of atrial fibrillation. Br Heart J . 1970;32:57-60.Crossref 6. Hillestad L, Bjerkelund C, Dale J, Maltau J, Storstein O. Quinidine in maintenance of sinus rhythm after electroconversion of chronic atrial fibrillation: a controlled clinical study. Br Heart J . 1971;33:518-521.Crossref 7. Lloyd EA, Gersh BJ, Forman R. The efficacy of quinidine and disopyramide in the maintenance of sinus rhythm after electroconversion from atrial fibrillation: a double-blind study comparing quinidine, disopyramide and placebo. S Afr Med J . 1984;65;367-369. 8. Södermark T, Jonsson B, Olsson A, et al. Effect of quinidine on maintaining sinus rhythm after conversion of atrial fibrillation or flutter: a multicentre study from Stockholm. Br Heart J . 1975;37:486-492.Crossref 9. Antman EM, Beamer AD, Cantillon C, McGowan N, Friedman PL. Therapy of refractory symptomatic atrial fibrillation and atrial flutter: a staged care approach with new antiarrhythmic drugs. J Am Coll Cardiol . 1990;15:698-707.Crossref 10. Juul-Moller S, Edvardsson N, Rehnqvist-Ahlberg N. Sotolol versus quinidine for the maintenance of sinus rhythm after direct current conversion of atrial fibrillation. Circulation . 1990;82:1932-1939.Crossref 11. Coplen SE, Antman EM, Berlin JA. Hewitt P, Chalmers TC. Efficacy and safety of quinidine therapy for maintenance of sinus rhythm after cardioversion: a meta-analysis of randomized control trials. Circulation . 1990;82:1106-1116.Crossref 12. Peterson P, Godtfredsen J, Boysen G, Anderson ED, Anderson B. Placebocontrolled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: the Copenhagen AFASAK Study. Lancet . 1989;1:175-178.Crossref 13. Stroke Prevention Atrial Fibrillation (SPAF) Investigators. Stroke prevention in atrial fibrillation study. Circulation . 1991;84:527-539.Crossref 14. Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) Investigators. The effect of low-dose warfarin on the risk of stroke in patients with nonrheumatic atrial fibrillation. N Engl J Med . 1990;323:1505-1511.Crossref 15. Canadian Atrial Fibrillation Anticoagulation (CAFA) Investigators. Canadian Atrial Fibrillation (CAFA) Study. J Am Coll Cardiol . 1991;18:349-355.Crossref 16. Veterans Affairs Stroke Prevention in Nonrheumatic Atrial Fibrillation (SPINAF) Investigators. Warfarin in the prevention of stroke associated with nonrheumatic atrial fibrillation. N Engl J Med . 1992;327:1406-1412.Crossref 17. Stroke Prevention in Atrial Fibrillation Investigators. Predictors of thromboembolism in atrial fibrillation, I: clinical features of patients at risk. Ann Intern Med . 1992;116:1-5.Crossref 18. Stroke Prevention in Atrial Fibrillation Investigators. Predictors of thromboembolism in atrial fibrillation, II: echocardiographic features of patients at risk. Ann Intern Med . 1992;116:6-12.Crossref 19. Kopecky SL, Gersh BJ, McGoon MD, et al. The natural history of lone atrial fibrillation. N Engl J Med . 1987;317:669-674.Crossref 20. Horowitz LN, Spielman SR, Greenspan AM, et al. Use of amiodarone in the treatment of persistent and paroxysmal atrial fibrillation resistant to quinidine therapy. J Am Coll Cardiol . 1985;6:1402-1407.Crossref 21. Gold RL, Haffajee Cl, Charos G, Sloan K, Baker S, Alpert JS. Amiodarone for refractory atrial fibrillation. Am J Cardiol . 1986;57:124-127.Crossref 22. Gosselink ATM, Crijns HJGM, Van Gelder IC, Hillige H, Wiesfeld ACP, Lie Kl. Low-dose amiodarone for maintenance of sinus rhythm after cardioversion of atrial fibrillation or flutter. JAMA . 1992;267:3289-3293.Crossref 23. Blevins RD, Kerin NZ, Benaderet D, et al. Amiodarone in the management of refractory atrial fibrillation. Arch Intern Med . 1987;147:1401-1404.Crossref 24. Brodsky MA, Allen BJ, Waler CJ, Casey TP, Luckett CR, Henry WL. Amiodarone for maintenance of sinus rhythm after conversion of atrial fibrillation in the setting of a dilated left atrium. Am J Cardiol . 1987;60:572-575.Crossref 25. Middlekauff HR, Wiener I, Saxon LA, Stevenson WG. Low-dose amiodarone for atrial fibrillation: time for a prospective study? Ann Intern Med . 1992;116: 1017-1020.Crossref 26. Middlekauff HR, Stevenson WG. Warfarin versus amiodarone for refractory atrial fibrillation: a decision analysis approach. Clin Res . 1993;41:77A. 27. Stroke Prevention in Atrial Fibrillation Investigators. Warfarin versus aspirin for prevention of thromboembolism in atrial fibrillation: Stroke Prevention in Atrial Fibrillation II Study. Lancet . 1994;343:687-691. 28. Martin A, Benbow LJ, Leach C, Bailey RJ. Comparison of amiodarone and disopyramide in the control of paroxysmal atrial fibrillation and atrial flutter (interim report). Br J Clin Pract Symp Suppl . 1986;44:52-60. 29. Kowey PR, Friehling TD, Marinchak RA, Sulpizi AM, Stohler JL. Safety and efficacy of amiodarone: the low-dose perspective. Chest . 1988:93:54-59.Crossref 30. Middlekauff HR, Stevenson WG, Saxon LA, Stevenson LW. Low-dose aminodarone for atrial fibrillation in advanced heart failure restores sinus rhythm and improves functional capacity. Circulation . 1992;86:I-808. 31. Disch DL, Greenberg ML, Holzberger PT, Malenka DJ, Birkmeyer JD. Managing chronic atrial fibrillation: a Markov decision analysis comparing warfarin, quinidine, and low-dose amiodarone. Ann Intern Med . 1994;120:449-457.Crossref 32. Chesebro JH, Fuster V, Halperin JL. Atrial fibrillation: risk marker for stroke. N Engl J Med . 1990;323:1556-1558.Crossref 33. Flaker GC, Blackshear JL, McBride R, Kronmal RA, Halperin JL, Hart RG. Antiarrhythmic drug therapy and cardiac mortality in atrial fibrillation. J Am Coll Cardiol . 1992;20:527-532.Crossref

Journal

Archives of Internal MedicineAmerican Medical Association

Published: May 8, 1995

References