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Anticoagulation*: American College of Chest Physicians Guidelines for the Prevention and Management of Postoperative Atrial Fibrillation After Cardiac Surgery FREE TO VIEW

Andrew E. Epstein, MD; John C. Alexander, MD; David D. Gutterman, MD, FCCP; William Maisel, MD, MPH; J. Marcus Wharton, MD
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*From the University of Alabama at Birmingham (Dr. Epstein), Birmingham, AL; Hackensack University Medical Center (Dr. Alexander), Hackensack, NJ; the Medical College of Wisconsin (Dr. Gutterman), Milwaukee, WI; Harvard University (Dr. Maisel), Boston, MA; and the Medical University of South Carolina (Dr. Wharton), Charleston, SC.

Correspondence to: Andrew E. Epstein, MD, Division of Cardiovascular Disease, Department of Medicine, The University of Alabama at Birmingham, Tinsley Harrison Tower 321L, 1530 Third Ave South, Birmingham, AL 35294-0006; e-mail: aepstein@uab.edu



Chest. 2005;128(2_suppl):24S-27S. doi:10.1378/chest.128.2_suppl.24S
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Post-cardiac surgery atrial fibrillation (AF) places patients at risk for thromboembolism and stroke, while the surgery and cardiopulmonary bypass alter the multiple factors of coagulation and may increase the tendency to bleed. It is in the context of this complex clinical picture that the physician must make decisions regarding the risks and benefits of anticoagulation therapy to lower the risk for thromboembolism and stroke associated with postoperative AF. Physicians must also weigh the usually transient and self-limited duration of new-onset postoperative AF against the potential for postoperative bleeding if anticoagulation therapy is started. No randomized, controlled clinical trials are available that specifically address the problem of anticoagulation therapy for the postoperative AF. In that context, recommendations are based on the established therapy for nonsurgical situations modified by the potential risk of bleeding in the postoperative patient.

In nonsurgical patients, atrial fibrillation (AF) predisposes the patient to atrial thrombus formation and stroke. Cardiac surgery, and cardiopulmonary bypass in particular, results in complex alterations of coagulation, including reductions in clotting factors, alterations in platelet function, and increases in fibrinolytic products. Therefore, the relative merits of anticoagulation therapy for AF in patients following cardiac surgery must be carefully weighed against the risks of an already enhanced bleeding tendency. No studies have directly assessed the risks or benefits of anticoagulation therapy for episodes of AF that occur in the early postoperative period following coronary artery bypass grafting (CABG). Published studies112 have reported the use of placebo, aspirin, dipyridamole, ticlopidine, warfarin, and combinations of these drugs, but all of these studies were designed to evaluate the effect on bypass graft patency, blood and blood product utilization, bleeding, and myocardial ischemia. Hence, some direction is needed for the use of anticoagulants in the management of AF.

Of 12 identified studies, which focused on CABG surgery112, only 4 included therapy with warfarin (the mainstay of treatment to prevent embolization in patients with chronic AF), and only 1 of these studies has been published since 1985. The demographics of the patients studied included a predominance of men with mean ages between 50 and 60 years. Because the risk of stroke and embolization is increased in patients who are > 65 years of age, particularly in older women, there may be limited applicability of these anticoagulation studies to the majority of patients with postoperative AF who are at an increased risk of stroke. These studies are also limited by the absence of detailed descriptions of inclusion and exclusion criteria, in addition to differences between control and treatment groups with regard to the medication regimens and therapeutic procedures used. Outcome criteria were often inadequately defined, and outcome assessments were not objective and were incompletely reported (total mortality was reported in only 7 of 12 studies). Of the 12 studies, the frequency of hemorrhagic stroke was reported in only 3, nonhemorrhagic stroke was reported in 4, transient ischemic attacks was reported in 2 studies, and non-CNS embolism was reported in 2 studies. In the four studies that included warfarin, the rate of stroke was reported in three (range, 0 to 1.8%), transient ischemic attacks were reported in 1 (0.7%), and non-CNS embolism was reported in none for patients who received warfarin. In summary, there are very few applicable studies in the literature that address the efficacy of anticoagulation therapy in patients undergoing CABG who experienced AF postoperatively.

The risk of stroke in patients with AF is closely related to the presence or absence of coexistent cardiovascular disease.1314 A history of stroke and/or transient ischemic attack, hypertension, congestive heart failure, advanced age, diabetes, and, notably, coronary artery disease predicts an increased embolic risk in patients with chronic AF.1314 The safety and efficacy of oral anticoagulation therapy with warfarin and/or aspirin for patients with sustained AF and one of these comorbidities have been well-documented.1315 The selection of appropriate anticoagulation therapy for patients with new-onset, chronic, or frequent AF is based on the perceived risk of thromboembolism (Table 1). ,13 The threshold of risk that is thought to justify anticoagulation therapy outside the postoperative setting is, however, controversial.1314 For patients with a perceived low risk for thromboembolism (ie, in patients who are < 60 years of age in whom none of the additional risk factors outlined above are present), the consensus is to treat with aspirin. For patients who are > 65 years of age in whom an additional risk factor (eg, coronary artery disease or heart failure) is present and/or for those patients who are ≥ 75 years of age, especially women, irrespective of additional risk factors, anticoagulation therapy with warfarin is recommended. The choice of anticoagulation therapy for patients in the intermediate category is controversial and depends on the opinion of the treating physician in conjunction with a discussion with the patient about the risks and benefits of therapy. In the aggregate, a metaanalysis,13 showed that oral anticoagulation therapy decreases the overall risk of stroke (both embolic and hemorrhagic) in patients with chronic AF by 61% (95% confidence interval, 47 to 71%) vs placebo. When patients who were undergoing anticoagulation therapy at the time of stroke were excluded, the preventive efficacy of oral anticoagulation therapy exceeded 80%.13 Thus, in optimally selected patients with chronic AF, anticoagulation therapy with warfarin is beneficial and appropriate. This recommendation also applies to patients with AF postoperatively, or those in whom AF is thought likely to continue postoperatively.

In patients with atrial flutter (AFL), the risk of thromboembolism is less well-established compared to the benefit of anticoagulation therapy in patients with chronic AF. The American College of Cardiology (ACC)/American Heart Association (AHA)/European Society of Cardiology (ESC) practice guideline,13 however, recommends that patients with AF and AFL be treated similarly. The data, however, are controversial. Furthermore, patients with paroxysmal AF have similar outcomes to those with either persistent or permanent AF and should also receive anticoagulation therapy.13

The majority of cardiovascular surgery is performed in patients with additive risk factors for stroke. Postoperative patients are actually a subset of the general population of patients with AF and AFL.13,16The occurrence of AF in patients following CABG surgery is associated with increased morbidity, cost, and length of hospital stay.17 Furthermore, the risks of stroke and peripheral embolization attributable to AF are difficult to separate from the risk of the operation. The concomitant preexistent morbid conditions also increase the overall risk for perioperative complications. Additionally, it is likely that the risk of embolization associated with AF is modulated by the nature of the surgery involved (eg, the use of the heart lung machine, which affects coagulability) and the concomitant use of other drugs like heparin, clopidogrel, and, in almost all cases, aspirin.

These ACC/AHA/ESC practice guideline recommendations must be viewed in the context of the usually transient and self-limited duration of postoperative AF and AFL, and must be weighed against the potential risk of bleeding associated with recent major surgery. In a population-based historical cohort study of nonsurgical patients,18 the frequency of complications of aspirin, warfarin, and IV heparin therapy for secondary stroke prevention showed that anticoagulant-related complication rates for warfarin were higher than those in referral-based studies and multicenter randomized clinical trials. After adjustment for the duration of therapy, however, complication rates for heparin were actually even higher than those for either aspirin or warfarin.18 Although the routine use of heparin has been deemed to be inadvisable in patients with postoperative AF due to an increased risk for bleeding, it should be considered in high-risk patients such as those with a history of stroke or transient ischemic attack (Table 1).,13 Trials using warfarin in the immediate post-CABG surgery period for the maintenance of graft patency have shown only a minimal additional risk for overt bleeding, but there was a higher rate of large pericardial effusions and cardiac tamponade in patients receiving warfarin compared to aspirin or placebo. This observation could be considered evidence that warfarin in postoperative patients is in fact associated with increased bleeding-related risks.17 Thus, the risk of receiving anticoagulation therapy in patients who are at special risk for bleeding, such as those with low platelet counts or prolonged excessive chest tube drainage, may outweigh any potential benefit of anticoagulation therapy to reduce the risk of stroke.

If AF persists for 48 h, patients should receive anticoagulation therapy with warfarin to achieve an international normalized ratio of 2.0 to 3.0 as recommended for nonoperative patients by the ACC/AHA/ESC guideline.13 Because of the bleeding risk associated with heparin, warfarin therapy may be started without heparin. Although the optimal duration of therapy has not been established, in general, if normal sinus rhythm returns, anticoagulation therapy can reasonably be stopped because its risks outweigh the potential benefits. Nevertheless, delaying the cessation of anticoagulation therapy for 1 month after the return of sinus rhythm may be prudent since it has been demonstrated that impaired atrial contraction, with a presumably enhanced risk for thrombosis, can persist for several weeks after AF ceases. The increasing use of amiodarone in the treatment of AF prompts a word of caution in those patients requiring warfarin therapy as well, and, because of a significant interaction, a 25 to 40% reduction in the warfarin dose may be required depending on the dose of amiodarone.19 In light of the lack of randomized trial data in the area of anticoagulation therapy in perioperative, AF emphasizes the need for further study in this area.

While the risk for atrial thrombus formation and stroke must be considered, the potential major complications of postoperative AF and AFL, anticoagulation must be considered in light of the complex alterations of coagulation and the risk for enhanced bleeding tendency associated with cardiac surgery and cardiopulmonary bypass. Thus, the relative merits of anticoagulation therapy in patients with AF after cardiac surgery must be weighed against (1) the potential risk for bleeding in a setting of an already enhanced bleeding tendency after major surgery and (2) the typically self-limited history of postoperative AF and AFL. Thus, recommendations for anticoagulation in postoperative patients with AF and AFL include the following (see Table 2 ).

  1. In optimally selected patients with chronic AF and in those patients in whom it is thought to be likely that AF will continue postoperatively, we recommend anticoagulation therapy (strength of recommendation, A; evidence grade, good; net benefit, substantial).

  2. In the high-risk patient with postoperative AF, such as those with a history of stroke or transient ischemic attack, the routine use of heparin should be considered (strength of recommendation, C; evidence grade, low; net benefit, intermediate).

  3. We recommend continuing anticoagulation therapy for 30 days after the return of normal sinus rhythm because of the prior demonstration of persistent impairment of atrial contraction and a presumably enhanced risk for thrombosis following the conversion of postoperative AF (strength of recommendation, C; evidence grade, low; net benefit, intermediate).

Abbreviations: ACC = American College of Cardiology; AF = atrial fibrillation; AFL = atrial flutter; AHA = American Heart Association; CABG = coronary artery bypass grafting; ESC = European Society of Cardiology

Table Graphic Jump Location
Table 1. Risk Stratification Schemes for Primary Prevention of Thromboembolism in Patients With Nonvalvular Atrial Fibrillation*
* 

Adapted from Fuster et al.13

Table Graphic Jump Location
Table 2. Summary of Recommendations
Pantely, GA, Goodnight, SH, Jr, Rahimtoola, SH, et al (1979) Failure of antiplatelet and anticoagulant therapy to improve patency of grafts after coronary-artery bypass: a controlled, randomized study.N Engl J Med301,962-966
 
Chesebro, JH, Clements, IP, Fuster, V, et al A platelet-inhibitor-drug trial in coronary-artery bypass operations: benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency.N Engl J Med1982;307,73-78
 
McEnany, MT, Salzman, EW, Mundth, ED, et al The effect of antithrombotic therapy on patency rates of saphenous vein coronary artery bypass grafts.J Thorac Cardiovasc Surg1982;83,81-89
 
Chevigne, M, David, JL, Rigo, P, et al Effect of ticlopidine on saphenous vein bypass patency rates: a double-blind study.Ann Thorac Surg1984;37,371-378
 
Lorenz, RL, Schacky, CV, Weber, M, et al Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily): effects on platelet aggregation and thromboxane formation.Lancet1984;1,1261-1264
 
Brooks, N, Wright, J, Sturridge, M, et al Randomised placebo controlled trial of aspirin and dipyridamole in the prevention of coronary vein graft occlusion.Br Heart J1985;53,201-207
 
Rothlin, ME, Pfluger, N, Speiser, K, et al Platelet inhibitors versus anticoagulants for prevention of aorto-coronary bypass graft occlusion.Eur Heart J1985;6,168-175
 
Sanz, G, Pajaron, A, Alegria, E, et al Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole: Grupo Espanol para el Seguimiento del Injerto Coronario (GESIC).Circulation1990;82,765-773
 
Sethi, GK, Copeland, JG, Goldman, S, et al Implications of preoperative administration of aspirin in patients undergoing coronary artery bypass grafting: Department of Veterans Affairs Cooperative Study on Antiplatelet Therapy.J Am Coll Cardiol1990;15,15-20
 
Teoh, KH, Weisel, RD, Ivanov, J, et al Dipyridamole for coronary artery bypass surgery.Thromb Res1990;12(suppl),91-99
 
Gavaghan, TP, Gebski, V, Baron, DW Immediate postoperative aspirin improves vein graft patency early and late after coronary artery bypass graft surgery. a placebo-controlled, randomized study.Circulation1991;83,1526-1533
 
van der Meer, J, Hillege, HL, Kootstra, GJ, et al Prevention of one-year vein-graft occlusion after aortocoronary-bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants: the CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.Lancet1993;342,257-264
 
Fuster, V, Rydén, LE, Asinger, RW, et al ACC/AHA/ESC 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).J Am Coll Cardiol2001;28,1231-1266
 
American College of Chest Physicians.. Sixth ACCP Consensus Conference on Antithrombotic Therapy.Chest2001;119(suppl),1S-370S
 
Hart, RG, Benavente, O, McBride, R, et al Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis.Ann Intern Med1999;131,492-501
 
Pearce, LA, Hart, RG, Halperin, JL Assessment of three schemes of stratifying stroke risk in patients with nonvalvular atrial fibrillation.Am J Med2000;109,45-51
 
Maisel, WH, Rawn, JD, Stevenson, WG Atrial fibrillation after cardiac surgery.Ann Intern Med2001;135,1061-1073
 
Petty, GW, Brown, RD, Whisnant, JP, et al Frequency of major complications of aspirin, warfarin, and intravenous heparin for secondary stroke prevention: a population-based study.Ann Intern Med1999;130,14-22
 
Sanoski, CA, Bauman, JL Clinical observations with the amiodarone/warfarin interaction: dosing relationship with long-term therapy.Chest2002;121,19-23
 

Figures

Tables

Table Graphic Jump Location
Table 1. Risk Stratification Schemes for Primary Prevention of Thromboembolism in Patients With Nonvalvular Atrial Fibrillation*
* 

Adapted from Fuster et al.13

Table Graphic Jump Location
Table 2. Summary of Recommendations

References

Pantely, GA, Goodnight, SH, Jr, Rahimtoola, SH, et al (1979) Failure of antiplatelet and anticoagulant therapy to improve patency of grafts after coronary-artery bypass: a controlled, randomized study.N Engl J Med301,962-966
 
Chesebro, JH, Clements, IP, Fuster, V, et al A platelet-inhibitor-drug trial in coronary-artery bypass operations: benefit of perioperative dipyridamole and aspirin therapy on early postoperative vein-graft patency.N Engl J Med1982;307,73-78
 
McEnany, MT, Salzman, EW, Mundth, ED, et al The effect of antithrombotic therapy on patency rates of saphenous vein coronary artery bypass grafts.J Thorac Cardiovasc Surg1982;83,81-89
 
Chevigne, M, David, JL, Rigo, P, et al Effect of ticlopidine on saphenous vein bypass patency rates: a double-blind study.Ann Thorac Surg1984;37,371-378
 
Lorenz, RL, Schacky, CV, Weber, M, et al Improved aortocoronary bypass patency by low-dose aspirin (100 mg daily): effects on platelet aggregation and thromboxane formation.Lancet1984;1,1261-1264
 
Brooks, N, Wright, J, Sturridge, M, et al Randomised placebo controlled trial of aspirin and dipyridamole in the prevention of coronary vein graft occlusion.Br Heart J1985;53,201-207
 
Rothlin, ME, Pfluger, N, Speiser, K, et al Platelet inhibitors versus anticoagulants for prevention of aorto-coronary bypass graft occlusion.Eur Heart J1985;6,168-175
 
Sanz, G, Pajaron, A, Alegria, E, et al Prevention of early aortocoronary bypass occlusion by low-dose aspirin and dipyridamole: Grupo Espanol para el Seguimiento del Injerto Coronario (GESIC).Circulation1990;82,765-773
 
Sethi, GK, Copeland, JG, Goldman, S, et al Implications of preoperative administration of aspirin in patients undergoing coronary artery bypass grafting: Department of Veterans Affairs Cooperative Study on Antiplatelet Therapy.J Am Coll Cardiol1990;15,15-20
 
Teoh, KH, Weisel, RD, Ivanov, J, et al Dipyridamole for coronary artery bypass surgery.Thromb Res1990;12(suppl),91-99
 
Gavaghan, TP, Gebski, V, Baron, DW Immediate postoperative aspirin improves vein graft patency early and late after coronary artery bypass graft surgery. a placebo-controlled, randomized study.Circulation1991;83,1526-1533
 
van der Meer, J, Hillege, HL, Kootstra, GJ, et al Prevention of one-year vein-graft occlusion after aortocoronary-bypass surgery: a comparison of low-dose aspirin, low-dose aspirin plus dipyridamole, and oral anticoagulants: the CABADAS Research Group of the Interuniversity Cardiology Institute of The Netherlands.Lancet1993;342,257-264
 
Fuster, V, Rydén, LE, Asinger, RW, et al ACC/AHA/ESC 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).J Am Coll Cardiol2001;28,1231-1266
 
American College of Chest Physicians.. Sixth ACCP Consensus Conference on Antithrombotic Therapy.Chest2001;119(suppl),1S-370S
 
Hart, RG, Benavente, O, McBride, R, et al Antithrombotic therapy to prevent stroke in patients with atrial fibrillation: a meta-analysis.Ann Intern Med1999;131,492-501
 
Pearce, LA, Hart, RG, Halperin, JL Assessment of three schemes of stratifying stroke risk in patients with nonvalvular atrial fibrillation.Am J Med2000;109,45-51
 
Maisel, WH, Rawn, JD, Stevenson, WG Atrial fibrillation after cardiac surgery.Ann Intern Med2001;135,1061-1073
 
Petty, GW, Brown, RD, Whisnant, JP, et al Frequency of major complications of aspirin, warfarin, and intravenous heparin for secondary stroke prevention: a population-based study.Ann Intern Med1999;130,14-22
 
Sanoski, CA, Bauman, JL Clinical observations with the amiodarone/warfarin interaction: dosing relationship with long-term therapy.Chest2002;121,19-23
 
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Introduction*: American College of Chest Physicians Guidelines for the Prevention and Management of Postoperative Atrial Fibrillation After Cardiac Surgery
Methodological Approach*: American College of Chest Physicians Guidelines for the Prevention and Management of Postoperative Atrial Fibrillation After Cardiac Surgery
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