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Antithrombotic and Thrombolytic Therapy, 8th Ed : ACCP Guidelines: ANTITHROMBOTIC AND THROMBOLYTIC THERAPY, 8TH ED: ACCP GUIDELINES |

Antithrombotic Therapy in Atrial Fibrillation*: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) FREE TO VIEW

Daniel E. Singer, MD; Gregory W. Albers, MD; James E. Dalen, MD, MPH, FCCP; Margaret C. Fang, MD, MPH; Alan S. Go, MD; Jonathan L. Halperin, MD; Gregory Y. H. Lip, MD; Warren J. Manning, MD
Author and Funding Information

*From the Clinical Epidemiology Unit (Dr. Singer), General Medicine Division, Massachusetts General Hospital, Boston, MA; Stanford University Medical Center (Dr. Albers), Palo Alto, CA; Professor Emeritus (Dr. Dalen), University of Arizona; University of California, San Francisco (Dr. Fang), San Francisco, CA; Division of Research (Dr. Go), Kaiser Permanente of Northern California, Oakland, CA; Mt. Sinai Medical Center (Dr. Halperin), New York, NY; Department of Medicine (Dr. Lip), University of Birmingham, Birmingham, UK; and Beth Israel Deaconess Medical Center (Dr. Manning), Boston, MA.

Correspondence to: Daniel E. Singer, MD, Clinical Epidemiology Unit, S50–9, Massachusetts General Hospital, Boston, MA 02114; e-mail: dsinger@partners.org



Chest. 2008;133(6_suppl):546S-592S. doi:10.1378/chest.08-0678
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This chapter about antithrombotic therapy in atrial fibrillation (AF) is part of the American College of Chest Physicians Evidence-Based Guidelines Clinical Practice Guidelines (8th Edition). Grade 1 recommendations indicate that most patients would make the same choice and Grade 2 suggests that individual patient’s values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2008; 133[suppl]:123S–131S). Among the key recommendations in this chapter are the following (all vitamin K antagonist [VKA] recommendations have a target international normalized ratio [INR] of 2.5; range 2.0–3.0, unless otherwise noted). In patients with AF, including those with paroxysmal AF, who have had a prior ischemic stroke, transient ischemic attack (TIA), or systemic embolism, we recommend long-term anticoagulation with an oral VKA, such as warfarin, because of the high risk of future ischemic stroke faced by this set of patients (Grade 1A). In patients with AF, including those with paroxysmal AF, who have two or more of the risk factors for future ischemic stroke listed immediately below, we recommend long-term anticoagulation with an oral VKA (Grade 1A). Two or more of the following risk factors apply: age >75 years, history of hypertension, diabetes mellitus, moderately or severely impaired left ventricular systolic function and/or heart failure. In patients with AF, including those with paroxysmal AF, with only one of the risk factors listed immediately above, we recommend long-term antithrombotic therapy (Grade 1A), either as anticoagulation with an oral VKA, such as warfarin (Grade 1A), or as aspirin, at a dose of 75–325 mg/d (Grade 1B). In these patients at intermediate risk of ischemic stroke we suggest a VKA rather than aspirin (Grade 2A). In patients with AF, including those with paroxysmal AF, age ≤75 years and with none of the other risk factors listed above, we recommend long-term aspirin therapy at a dose of 75–325 mg/d (Grade 1B), because of their low risk of ischemic stroke. For patients with atrial flutter, we recommend that antithrombotic therapy decisions follow the same risk-based recommendations as for AF (Grade 1C). For patients with AF and mitral stenosis, we recommend long-term anticoagulation with an oral VKA (Grade 1B). For patients with AF and prosthetic heart valves we recommend long-term anticoagulation with an oral VKA at an intensity appropriate for the specific type of prosthesis (Grade 1B). See CHEST 2008; 133(suppl):593S–629S. For patients with AF of ≥48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA, such as warfarin, for 3 weeks before elective cardioversion and for at least 4 weeks after sinus rhythm has been maintained (Grade 1C). For patients with AF of ≥ 48 h or of unknown duration undergoing pharmacological or electrical cardioversion, we also recommend either immediate anticoagulation with unfractionated IV heparin, or low-molecular-weight heparin (LMWH), or at least 5 days of warfarin by the time of cardioversion (achieving an INR of 2.0–3.0) as well as a screening multiplane transesophageal echocardiography (TEE). If no thrombus is seen, cardioversion is successful, and sinus rhythm is maintained, we recommend anticoagulation for at least 4 weeks. If a thrombus is seen on TEE, then cardioversion should be postponed and anticoagulation should be continued indefinitely. We recommend obtaining a repeat TEE before attempting later cardioversion (Grade 1B addressing the equivalence of TEE-guided vs non–TEE-guided cardioversion). For patients with AF of known duration <48 h, we suggest cardioversion without prolonged anticoagulation (Grade 2C). However, in patients without contraindications to anticoagulation, we suggest beginning IV heparin or LMWH at presentation (Grade 2C).

1.1 AF

1.1.1. In patients with AF, including those with paroxysmal AF, who have had a prior ischemic stroke, TIA, or systemic embolism, we recommend long-term anticoagulation with an oral vitamin K antagonist, such as warfarin, targeted at an INR of 2.5 (range, 2.0 to 3.0) because of the high risk of future ischemic stroke faced by this set of patients (Grade 1A). Timing of the initiation of VKA therapy after an acute ischemic stroke involves balancing the risk of hemorrhagic conversion with short-term risk of recurrent ischemic stroke and is addressed in the chapter by Albers et al in this supplement. 1.1.2. In patients with AF, including those with paroxysmal AF, who have two or more of the following risk factors for future ischemic stroke, we recommend long-term anticoagulation with an oral VKA, such as warfarin, targeted at an INR of 2.5 (range, 2.0 to 3.0) because of the increased risk of future ischemic stroke faced by this set of patients (Grade 1A). Two or more of the following risk factors apply: (1) age > 75 years; (2) history of hypertension; (3) diabetes mellitus; and (4) moderately or severely impaired left ventricular systolic function and/or heart failure.

Remark: Recommendations 1.1.1 and 1.1.2 correspond to a recommendation of oral VKA therapy for individuals with a score ≥ 2 using the CHADS2 classification. For these and all other recommendations of long-term therapy in this chapter, long-term means lifelong unless a contraindication emerges.

1.1.3. In patients with AF, including those with paroxysmal AF, with only one of the risk factors listed below, we recommend long-term antithrombotic therapy (Grade 1A), either as anticoagulation with an oral VKA, such as warfarin, targeted at an INR of 2.5 (range, 2.0 to 3.0) (Grade 1A), or as aspirin, at a dose of 75 to 325 mg/d (Grade 1B). For these patients at intermediate risk of ischemic stroke, we suggest a VKA rather than aspirin (Grade 2A). This set of patients with AF is defined by having one of the following risk factors: (1) age > 75 years; (2) history of hypertension; (3) diabetes mellitus; or (4) moderately or severely impaired left ventricular systolic function and/or heart failure. 1.1.4. In patients with AF, including those with paroxysmal AF, aged ≤ 75 years and with none of the other risk factors listed above, we recommend long-term aspirin therapy at a dose of 75 to 325 mg/d (Grade 1B) because of their low risk of ischemic stroke.

Underlying values and preferences: Anticoagulation with oral VKAs, such as warfarin, has far greater efficacy than aspirin in preventing stroke, and particularly in preventing severe ischemic stroke, in AF. We recommend the option of aspirin therapy for lower risk groups in 1.1.3 and 1.1.4, above, estimating the absolute expected benefit of anticoagulant therapy may not be worth the increased hemorrhagic risk and burden of anticoagulation. Individual lower-risk patients may rationally choose anticoagulation over aspirin therapy to gain greater protection against ischemic stroke if they value protection against stroke much more highly than reducing risk of hemorrhage and the burden of managing anticoagulation. Our recommendations assume that the patient is not at high risk for bleeding and that good control of anticoagulation will occur.

Remarks: These recommendations apply to patients with persistent or paroxysmal AF and not to patients with a single brief episode of AF due to a reversible cause, such as an acute pulmonary infection. The optimal dose of aspirin for patients with AF is unclear. The largest effect of aspirin was seen in the first Stroke Prevention in Atrial Fibrillation (SPAF I) trial, which used aspirin at 325 mg/d.1 However, generalizing from trials of aspirin for all antithrombotic indications and from physiologic studies, we feel the best balance of efficacy and safety is achieved at low doses of aspirin, ie, 75 to 100 mg/d (see chapter on “Antiplatelet Drugs” in this supplement).2

1.2 Atrial Flutter

1.2. For patients with atrial flutter, we recommend that antithrombotic therapy decisions follow the same risk-based recommendations as for AF (Grade 1C).

1.3 Valvular Heart Disease and AF

1.3.1. For patients with AF and mitral stenosis, we recommend long-term anticoagulation with an oral VKA, such as warfarin (target INR, 2.5; range, 2.0 to 3.0) [Grade 1B].

1.3.2. For patients with AF and prosthetic heart valves we recommend long-term anticoagulation with an oral VKA, such as warfarin, at an intensity appropriate for the specific type of prosthesis (Grade 1B). See chapter on “Valvular and Structural Heart Disease” in this supplement.

1.4 AF Following Cardiac Surgery

1.4. For patients with AF occurring shortly after open-heart surgery and lasting ≥ 48 h, we suggest anticoagulation with an oral VKA, such as warfarin, if bleeding risks are acceptable (Grade 2C). The target INR is 2.5 (range, 2.0 to 3.0). We suggest continuing anticoagulation for 4 weeks following reversion to and maintenance of normal sinus rhythm (NSR), particularly if patients have risk factors for thromboembolism (Grade 2C).

2.1 Anticoagulation for Elective Cardioversion of AF

2.1.1. For patients with AF of ≥ 48 h or of unknown duration for whom pharmacologic or electrical cardioversion is planned, we recommend anticoagulation with an oral VKA, such as warfarin, at a target INR of 2.5 (range, 2.0 to 3.0) for 3 weeks before elective cardioversion and for at least 4 weeks after sinus rhythm has been maintained (Grade 1C).