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Stroke Prevention in Nonvalvular Atrial Fibrillation FREE

Gregory W. Albers, MD; J. Edwin Atwood, MD; Jack Hirsh, MD; David G. Sherman, MD; Robert A. Hughes, MD; and Stuart J. Connolly, MD
[+] Article and Author Information

Grant Support: The symposium was supported in part by an educational grant from DuPont Pharmaceuticals.

Requests for Reprints: Greg Albers, MD, Neurology (127), Palo Alto Veterans Affairs Medical Center, Palo Alto, CA 94304.

Current Author Addresses: Dr. Albers: Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, CA 94305.

Dr. Atwood: Division of Cardiology, Stanford University Medical Center, Stanford, CA 94305.

Dr. Connolly: Faculty of Health Science, McMaster University, Hamilton, Ontario L8L 2X2.

Dr. Hirsh: Hamilton Civic Hospital Research Center, Hamilton, Ontario L8V 1C3.

Dr. Hughes: 275 Cambridge Street, Suite 200, Boston, MA 02114. Dr. Sherman: Division of Neurology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78284.


Ann Intern Med. 1991;115(9):727-736. doi:10.7326/0003-4819-115-9-727
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Abstract

▪ There has been considerable uncertainty about the best way to prevent stroke in patients with nonvalvular atrial fibrillation. Recent studies have suggested that low-dose warfarin therapy, in addition to producing fewer bleeding complications, may be as effective as higher-dose therapy in preventing thromboembolic events. Four large, prospective, randomized trials have examined the risks and benefits of warfarin therapy for stroke prophylaxis in patients with nonvalvular atrial fibrillation. All four studies showed a substantially reduced incidence of stroke and a low incidence of significant bleeding in patients treated with warfarin. One of these studies also showed that aspirin reduced the incidence of stroke. The benefits associated with long-term low-dose warfarin therapy appear to exceed the risks for serious bleeding in most patients with atrial fibrillation. Aspirin may be a viable therapeutic option for patients who are unable to take warfarin or for those in subgroups at a low risk for stroke.

References

Dunn M, Alexander J, de Silva R, Hildner F . Antithrombotic therapy in atrial fibrillation. Chest.. 1989; ;95::118S--27S. .
CrossRef
 
Kannel WB, Abbott RD, Savage DD, McNamara PM . Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med.. 1982; ;306::1018--22. .
 
Kitchens JM, Flegel KM . Atrial fibrillation, stroke and anticoagulation: what is to be done? J Gen Intern Med.. 1986; ;1::126--9. .
 
Cerebral Embolism Task Force . Cardiogenic brain embolism. The second report of the Cerebral Embolism Task Force. Arch Neurol.. 1989; ;46::727--43. .
 
Cerebral Embolism Task Force . Cardiogenic brain embolism. Arch Neurol.. 1986; ;43::71--84. .
 
Kulbertus HE, Olsson SB, Schlepper M eds.Atrial Fibrillation.. Molndal, Sweden: :A. B. Hassle; ;1982..
 
Meijler FL . Atrial fibrillation: a new look at an old arrhythmia. J Am Coll Cardiol.. 1983; ;2::391--3. .
 
Fuster V, Gersh BJ, Guiliana ER . The natural history of idiopathic dilated cardiomyopathy. Am J Cardiol.. 1981; ;47::525--31. .
 
Glancy DL, O'Brien KP, Gold HK, Epstein SE . Atrial fibrillation in patients with idiopathic hypertrophic subaortic stenosis. Br Heart J.. 1970; ;32::652--9. .
 
Presti CF, Hart RG . Thyrotoxicosis, atrial fibrillation, and embolism, revisited. Am Heart J.. 1989; ;117::976--97. .
 
Hurst JW . The examination of the heart: the importance of initial screening. Dis Mon.. 1990; ;36::251--313. .
 
Matsuzaki M, Toma Y, Reizo K . Clinical applications of transesophageal echocardiography. Circulation.. 1990; ;82::709--22. .
 
Dittrich HC, Erickson JS, Schneiderman T, Blacky AR, Savides T, Nicod PH . Echocardiographic and clinical predictors for outcome of elective cardioversion of atrial fibrillation. Am J Cardiol.. 1989; ;63::193--7. .
 
Brodsky MA, Allen BJ, Capparelli EV, Luckett CR, Morton R, Henry WL . Factors determining maintenance of sinus rhythm after chronic atrial fibrillation with left atrial dilatation. Am J Cardiol.. 1989; ;63::1065--8. .
 
Bjerkelund CJ, Orning OM . The efficacy of anticoagulant therapy in preventing embolism related to D.C. electrical conversion of atrial fibrillation. Am J Cardiol.. 1969; ;23::208--16. .
 
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--16. .
 
Platia EV, Michelson EL, Porterfield JK, Das G . Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter. Am J Cardiol.. 1989; ;63::925--9. .
 
Atwood JE, Myers JN, Sullivan MJ, Forbes SM, Pewen WF . Diltiazem and exercise performance in patients with chronic atrial fibrillation. Chest. 1988; ;93::20--5. .
 
Atwood JE, Sullivan MJ, Forbes S, Myers J, Pewen W, Olson HG et al. . Effect of beta-adrenergic blockade on exercise performance in patients with chronic atrial fibrillation. J Am Coll Cardiol.. 1987; ;10::314--20. .
 
Hirsh J, Poller L, Deykin D, Levine M, Dalen JE . Optimal therapeutic range for oral anticoagulants. Chest.. 1989; ;95::5S--10S. .
 
Hirsh J . Is the dose of warfarin prescribed by American physicians unnecessarily high? Arch Intern Med.. 1987; ;147::767--77. .
 
Quick AJ . The prothrombin time in haemophilia and in obstructive jaundice. J Biol Chem.. 1935; ;109::73--4. .
 
Zucker S, Cathey MH, Sox PJ, Hall EC . Standardization of laboratory tests for controlling anticoagulant therapy. Am J Clin Pathol.. 1970; ;53::348--54. .
 
Poller L . Progress in standardization in anticoagulant control. Hematol Rev.. 1987; ;225::41..
 
Hirsh J, Levine M . Confusion over the therapeutic range for monitoring oral anticoagulant therapy in North America. Thromb Haemost.. 1988; ;59::129--32. .
 
Wright IS, Beck DF, Marple CD . Myocardial infarction and its treatment with anticoagulant: summary of findings in 1031 cases. Lancet.. 1954; ;1::92--105. .
 
Kirkwood TB . Calibration of reference thromboplastins and standardisation of the prothrombin time ratio. Thromb Haemost.. 1983; ;49::238--44. .
 
O'Reilly RA, Pool JG, Aggeler PM . Hereditary resistance to coumarin anticoagulant drugs in man and rat. Ann NY Acad Sci.. 1968; ;151::913--1031. .
 
Deykin D . Warfarin therapy. N Engl J Med. 1970; ;283::801--3. .
 
Breckenridge AM . Interindividual differences in the responses of oral anticoagulants. Drug.. 1977; ;12::367--75. .
 
Brozovic M . Oral anticoagulants in clinical practice. Semin Hematol.. 1978; ;15::27--34. .
 
Hellemans J, Vorlat M, Verstraete M . Survival time of prothrombin and factors VII, IX, and X after complete synthesis blocking doses of coumarin derivatives. Br J Haematol.. 1963; ;9::506--12. .
 
Vigano S, Mannucci PM, Solinas S, Bottasso B, D'Angela A, Mariani G . Early fall of protein C during short-term anticoagulant treatment. Thromb Haemost.. 1983; ;50::310..
 
Wolf PA, Dawber TR, Thomas HE Jr, Kannel WB . Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology.. 1978; ;28::973--7. .
 
Levine HJ, Pauker SG, Salzman EW . Antithrombotic therapy in valvular heart disease. Chest.. 1989; ;95:( (2 Suppl) ):98S--106S. .
 
Wolf PA, Abbott RD, Kannel WB . Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham study. Arch Intern Med.. 1987; ;147::1561--4. .
 
Flegel KM, Hanley J . Risk factors for stroke and other embolic events in patients with nonrheumatic atrial fibrillation. Stroke.. 1989; ;20::1000--4. .
 
Kopecky SL, Gerah BJ, McGoon MD, Whisnant JP, Holmes Dr Jr, Ilstrup DM et al. . The natural history of lone atrial fibrillation. N Engl J Med.. 1987; ;317::669--74. .
 
Close JB, Evans DW, Bailey SM . Persistent lone atrial fibrillationits prognosis after clinical diagnosis. J R Coll Gen Pract.. 1979; ;29::547--9. .
 
Brand FN, Abbott RD, Kannel WB, Wolf PA . Characteristics and prognosis of lone atrial fibrillation. JAMA.. 1985; ;254::3449--53. .
 
Petersen P . Thromboembolic complications in atrial fibrillation. Stroke.. 1990; ;21::4--13. .
 
Sherman DG, Goldman L, Whiting RB, Jurgensen K, Kaste M, Easton JD . Thromboembolism in patients with atrial fibrillation. Arch Neurol.. 1984; ;41::708--10. .
 
Roy D, Marchand E, Gagne P, Chabot M, Cartier R . Usefulness of anticoagulant therapy in the prevention of embolic complications of atrial fibrillation. Am Heart J.. 1986; ;112::1139--43. .
 
Wiener I . Clinical and echocardiographic correlates of systemic embolization in nonrheumatic atrial fibrillation. Am J Cardiol.. 1987; ;59::177..
 
Tegeler CH, Hart RG . Atrial size, atrial fibrillation and stroke. Ann Neurol.. 1987; ;21::315--6. .
 
Aronow WS, Gustein H, Hsieh FY . Risk factors for thromboembolic stroke in elderly patients with chronic atrial fibrillation. Am J Cardiol.. 1989; ;63::366--7. .
 
D'Olhaberriague L, Hernandex-Vidal A, Molina L, Soler-Singla L, Marrugat J, Pons S et al. . A prospective study of atrial fibrillation and stroke. Stroke.. 1989; ;20::1648--52. .
 
de Beider MA, Tourikis L, Leech G, Camm AJ . Spontaneous contrast echos are markers of thromboembolic risk in patients with atrial fibrillation [Abstract]. Circulation.. 1989; ;80::S1..
 
Malone SA, Palac RT, Imus RL, Andrilenas KK, McDonald RW, Giraud GD . Prevalence of left atrial thrombi in symptomatic versus asymptomatic patients with nonvalvular atrial fibrillation [Abstract]. Circulation.. 1989; ;80::S1..
 
Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B . Placebo-controlled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: The Copenhagen AFASAK study. Lancet.. 1989; ;1::175--8. .
 
Albers GW, Sherman DG, Gress DR, Paulseth JE, Petersen P . Stroke prevention in nonvalvular atrial fibrillation: a review of prospective randomized trials. Ann Neurol.. 1991; ;30::511--8. .
 
Petersen P, Kastrup J, Helweg-Larsen S, Boysen G, Godtfredsen J . Risk factors for thromboembolic complications in chronic atrial fibrillation: The Copenhagen AFASAK study. Arch Intern Med.. 1990; ;150::819--21. .
 
The Stroke Prevention in Atrial Fibrillation Investigators . Stroke prevention in atrial fibrillation study: final results. Circulation.. 1991; ;84::527--39. .
 
The Boston Area Anticoagulation Trial for Atrial Fibrillation 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--11. .
 
Connolly SJ, Laupacis A, Gent M et al. . Canadian atrial fibrillation anticoagulation (CAFA) study. J Am Coll Cardiol.. 1991; ;18::349--55. .
 

Figures

Tables

References

Dunn M, Alexander J, de Silva R, Hildner F . Antithrombotic therapy in atrial fibrillation. Chest.. 1989; ;95::118S--27S. .
CrossRef
 
Kannel WB, Abbott RD, Savage DD, McNamara PM . Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med.. 1982; ;306::1018--22. .
 
Kitchens JM, Flegel KM . Atrial fibrillation, stroke and anticoagulation: what is to be done? J Gen Intern Med.. 1986; ;1::126--9. .
 
Cerebral Embolism Task Force . Cardiogenic brain embolism. The second report of the Cerebral Embolism Task Force. Arch Neurol.. 1989; ;46::727--43. .
 
Cerebral Embolism Task Force . Cardiogenic brain embolism. Arch Neurol.. 1986; ;43::71--84. .
 
Kulbertus HE, Olsson SB, Schlepper M eds.Atrial Fibrillation.. Molndal, Sweden: :A. B. Hassle; ;1982..
 
Meijler FL . Atrial fibrillation: a new look at an old arrhythmia. J Am Coll Cardiol.. 1983; ;2::391--3. .
 
Fuster V, Gersh BJ, Guiliana ER . The natural history of idiopathic dilated cardiomyopathy. Am J Cardiol.. 1981; ;47::525--31. .
 
Glancy DL, O'Brien KP, Gold HK, Epstein SE . Atrial fibrillation in patients with idiopathic hypertrophic subaortic stenosis. Br Heart J.. 1970; ;32::652--9. .
 
Presti CF, Hart RG . Thyrotoxicosis, atrial fibrillation, and embolism, revisited. Am Heart J.. 1989; ;117::976--97. .
 
Hurst JW . The examination of the heart: the importance of initial screening. Dis Mon.. 1990; ;36::251--313. .
 
Matsuzaki M, Toma Y, Reizo K . Clinical applications of transesophageal echocardiography. Circulation.. 1990; ;82::709--22. .
 
Dittrich HC, Erickson JS, Schneiderman T, Blacky AR, Savides T, Nicod PH . Echocardiographic and clinical predictors for outcome of elective cardioversion of atrial fibrillation. Am J Cardiol.. 1989; ;63::193--7. .
 
Brodsky MA, Allen BJ, Capparelli EV, Luckett CR, Morton R, Henry WL . Factors determining maintenance of sinus rhythm after chronic atrial fibrillation with left atrial dilatation. Am J Cardiol.. 1989; ;63::1065--8. .
 
Bjerkelund CJ, Orning OM . The efficacy of anticoagulant therapy in preventing embolism related to D.C. electrical conversion of atrial fibrillation. Am J Cardiol.. 1969; ;23::208--16. .
 
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--16. .
 
Platia EV, Michelson EL, Porterfield JK, Das G . Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter. Am J Cardiol.. 1989; ;63::925--9. .
 
Atwood JE, Myers JN, Sullivan MJ, Forbes SM, Pewen WF . Diltiazem and exercise performance in patients with chronic atrial fibrillation. Chest. 1988; ;93::20--5. .
 
Atwood JE, Sullivan MJ, Forbes S, Myers J, Pewen W, Olson HG et al. . Effect of beta-adrenergic blockade on exercise performance in patients with chronic atrial fibrillation. J Am Coll Cardiol.. 1987; ;10::314--20. .
 
Hirsh J, Poller L, Deykin D, Levine M, Dalen JE . Optimal therapeutic range for oral anticoagulants. Chest.. 1989; ;95::5S--10S. .
 
Hirsh J . Is the dose of warfarin prescribed by American physicians unnecessarily high? Arch Intern Med.. 1987; ;147::767--77. .
 
Quick AJ . The prothrombin time in haemophilia and in obstructive jaundice. J Biol Chem.. 1935; ;109::73--4. .
 
Zucker S, Cathey MH, Sox PJ, Hall EC . Standardization of laboratory tests for controlling anticoagulant therapy. Am J Clin Pathol.. 1970; ;53::348--54. .
 
Poller L . Progress in standardization in anticoagulant control. Hematol Rev.. 1987; ;225::41..
 
Hirsh J, Levine M . Confusion over the therapeutic range for monitoring oral anticoagulant therapy in North America. Thromb Haemost.. 1988; ;59::129--32. .
 
Wright IS, Beck DF, Marple CD . Myocardial infarction and its treatment with anticoagulant: summary of findings in 1031 cases. Lancet.. 1954; ;1::92--105. .
 
Kirkwood TB . Calibration of reference thromboplastins and standardisation of the prothrombin time ratio. Thromb Haemost.. 1983; ;49::238--44. .
 
O'Reilly RA, Pool JG, Aggeler PM . Hereditary resistance to coumarin anticoagulant drugs in man and rat. Ann NY Acad Sci.. 1968; ;151::913--1031. .
 
Deykin D . Warfarin therapy. N Engl J Med. 1970; ;283::801--3. .
 
Breckenridge AM . Interindividual differences in the responses of oral anticoagulants. Drug.. 1977; ;12::367--75. .
 
Brozovic M . Oral anticoagulants in clinical practice. Semin Hematol.. 1978; ;15::27--34. .
 
Hellemans J, Vorlat M, Verstraete M . Survival time of prothrombin and factors VII, IX, and X after complete synthesis blocking doses of coumarin derivatives. Br J Haematol.. 1963; ;9::506--12. .
 
Vigano S, Mannucci PM, Solinas S, Bottasso B, D'Angela A, Mariani G . Early fall of protein C during short-term anticoagulant treatment. Thromb Haemost.. 1983; ;50::310..
 
Wolf PA, Dawber TR, Thomas HE Jr, Kannel WB . Epidemiologic assessment of chronic atrial fibrillation and risk of stroke: the Framingham study. Neurology.. 1978; ;28::973--7. .
 
Levine HJ, Pauker SG, Salzman EW . Antithrombotic therapy in valvular heart disease. Chest.. 1989; ;95:( (2 Suppl) ):98S--106S. .
 
Wolf PA, Abbott RD, Kannel WB . Atrial fibrillation: a major contributor to stroke in the elderly. The Framingham study. Arch Intern Med.. 1987; ;147::1561--4. .
 
Flegel KM, Hanley J . Risk factors for stroke and other embolic events in patients with nonrheumatic atrial fibrillation. Stroke.. 1989; ;20::1000--4. .
 
Kopecky SL, Gerah BJ, McGoon MD, Whisnant JP, Holmes Dr Jr, Ilstrup DM et al. . The natural history of lone atrial fibrillation. N Engl J Med.. 1987; ;317::669--74. .
 
Close JB, Evans DW, Bailey SM . Persistent lone atrial fibrillationits prognosis after clinical diagnosis. J R Coll Gen Pract.. 1979; ;29::547--9. .
 
Brand FN, Abbott RD, Kannel WB, Wolf PA . Characteristics and prognosis of lone atrial fibrillation. JAMA.. 1985; ;254::3449--53. .
 
Petersen P . Thromboembolic complications in atrial fibrillation. Stroke.. 1990; ;21::4--13. .
 
Sherman DG, Goldman L, Whiting RB, Jurgensen K, Kaste M, Easton JD . Thromboembolism in patients with atrial fibrillation. Arch Neurol.. 1984; ;41::708--10. .
 
Roy D, Marchand E, Gagne P, Chabot M, Cartier R . Usefulness of anticoagulant therapy in the prevention of embolic complications of atrial fibrillation. Am Heart J.. 1986; ;112::1139--43. .
 
Wiener I . Clinical and echocardiographic correlates of systemic embolization in nonrheumatic atrial fibrillation. Am J Cardiol.. 1987; ;59::177..
 
Tegeler CH, Hart RG . Atrial size, atrial fibrillation and stroke. Ann Neurol.. 1987; ;21::315--6. .
 
Aronow WS, Gustein H, Hsieh FY . Risk factors for thromboembolic stroke in elderly patients with chronic atrial fibrillation. Am J Cardiol.. 1989; ;63::366--7. .
 
D'Olhaberriague L, Hernandex-Vidal A, Molina L, Soler-Singla L, Marrugat J, Pons S et al. . A prospective study of atrial fibrillation and stroke. Stroke.. 1989; ;20::1648--52. .
 
de Beider MA, Tourikis L, Leech G, Camm AJ . Spontaneous contrast echos are markers of thromboembolic risk in patients with atrial fibrillation [Abstract]. Circulation.. 1989; ;80::S1..
 
Malone SA, Palac RT, Imus RL, Andrilenas KK, McDonald RW, Giraud GD . Prevalence of left atrial thrombi in symptomatic versus asymptomatic patients with nonvalvular atrial fibrillation [Abstract]. Circulation.. 1989; ;80::S1..
 
Petersen P, Boysen G, Godtfredsen J, Andersen ED, Andersen B . Placebo-controlled, randomized trial of warfarin and aspirin for prevention of thromboembolic complications in chronic atrial fibrillation: The Copenhagen AFASAK study. Lancet.. 1989; ;1::175--8. .
 
Albers GW, Sherman DG, Gress DR, Paulseth JE, Petersen P . Stroke prevention in nonvalvular atrial fibrillation: a review of prospective randomized trials. Ann Neurol.. 1991; ;30::511--8. .
 
Petersen P, Kastrup J, Helweg-Larsen S, Boysen G, Godtfredsen J . Risk factors for thromboembolic complications in chronic atrial fibrillation: The Copenhagen AFASAK study. Arch Intern Med.. 1990; ;150::819--21. .
 
The Stroke Prevention in Atrial Fibrillation Investigators . Stroke prevention in atrial fibrillation study: final results. Circulation.. 1991; ;84::527--39. .
 
The Boston Area Anticoagulation Trial for Atrial Fibrillation 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--11. .
 
Connolly SJ, Laupacis A, Gent M et al. . Canadian atrial fibrillation anticoagulation (CAFA) study. J Am Coll Cardiol.. 1991; ;18::349--55. .
 

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