The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios.
We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement.
For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS2 [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS2 score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS2 score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy.
Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS2 score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach.
From the Department of Medicine (Drs You, Schulman, and Spencer) and Department of Clinical Epidemiology and Biostatistics (Dr You), McMaster University, Hamilton, ON, Canada; Department of Medicine (Dr Singer), Harvard Medical School, and Clinical Epidemiology Unit (Dr Singer), General Medicine Division, Massachusetts General Hospital, Boston, MA; School of Pharmacy (Dr Howard), University of Kansas Medical Center, Kansas City, KS; University of Birmingham Centre for Cardiovascular Sciences (Drs Lane and Lip), City Hospital, Birmingham, England; Department of Clinical Medicine (Dr Eckman), Division of General Internal Medicine and Center for Clinical Effectiveness, University of Cincinnati, Cincinnati, OH; Department of Medicine (Dr Fang), Division of Hospital Medicine, University of California, San Francisco, San Francisco, CA; Boston University Medical Center Research Unit (Dr Hylek), Section of General Internal Medicine, Boston, MA; Comprehensive Clinical Research Unit (Dr Go), Division of Research, Kaiser Permanente Northern California, Oakland, CA; Decision Resources Inc (Dr Hughes), London, England; Section of Non-invasive Cardiac Imaging (Dr Manning), Beth Israel Deaconess Medical Center, Boston, MA; and The Cardiovascular Institute (Dr Halperin), Mount Sinai Medical Center, New York, NY.
Correspondence to: Gregory Y. H. Lip, MD, University of Birmingham Centre for Cardiovascular Sciences, City Hospital, Birmingham, B18 7QH, England; e-mail: firstname.lastname@example.org
Author contributions: As Topic Editor, Dr You oversaw the development of this article, including the data analysis and subsequent development of the recommendations contained herein.
Dr You: contributed as Topic Editor.
Dr Singer: contributed as a panelist.
Dr Howard: contributed as a panelist.
Dr Lane: contributed as a panelist.
Dr Eckman: contributed as a resource consultant.
Dr Fang: contributed as a panelist.
Dr Hylek: contributed as a panelist.
Dr Schulman: contributed as a panelist.
Dr Go: contributed as a panelist.
Dr Hughes: contributed as a panelist.
Dr Spencer: contributed as a panelist.
Dr Manning: contributed as a panelist.
Dr Halperin: contributed as a panelist.
Dr Lip: contributed as Deputy Editor and senior author.
Financial/nonfinancial disclosures: The authors of this guideline provided detailed conflict of interest information related to each individual recommendation made in this article. A grid of these disclosures is available online at http://chestjournal.chestpubs.org/content/141/2_suppl/e531S/suppl/DC1. In summary, Dr Whitlock served on the advisory board for AstraZeneca in 2010 and served as a consultant for Boehringer Ingelheim for experimental anticoagulant study in mechanical valves; neither activity is related to the contents of this article. Dr Sun received funds from the University of Washington for research. Drs Freme, Rubens, and Teoh have reported to CHEST the following conflicts of interest: Over the past 3 years, Dr Singer has received grant support from the Eliot B. and Edith C. Shoolman fund of Massachusetts General Hospital (MGH) to study stroke in atrial fibrillation. He has also received research grant support (through MGH) from Daiichi-Sankyo, Inc, to study hemorrhage risk in patients with atrial fibrillation taking warfarin. Dr Singer has been supported by the National Institutes of Health (National Heart, Lung, and Blood Institute and National Institute on Aging) grant funding to study stroke risk in patients with atrial fibrillation. He has served as a consultant on stroke prevention in atrial fibrillation to Bayer Healthcare Pharmaceuticals; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Daiichi-Sankyo, Inc; Johnson & Johnson; Merck and Co, Inc; Pfizer Inc; and Sanofi-Aventis LLC. Dr. Singer has published numerous articles on stroke prevention in atrial fibrillation and has given numerous lectures and research presentations on this topic. Dr Lane is in receipt of an investigator-initiated educational grant from Bayer Healthcare Pharmaceuticals and has participated in speaker activities for Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim GmbH, Bristol-Myers Squibb/Pfizer Inc, and the Thrombosis Research Institute. She has also received support (travel and accommodation) to attend conferences from AstraZeneca and Boehringer Ingelheim GmbH. Dr Eckman has received a number of grants, including university grants for “Using Decision Analytic Modeling to Guide the ACCP Guideline Development Process for Antithrombotic Therapy in Atrial Fibrillation” (Foundation for Informed Medical Decision Making; $185,000) and has the following industry grants: “Cost-Effectiveness of Screening for Chronic Hepatitis C Infection” (Merck/Schering-Plough; September 2012; $58,000) and “Cost-Effectiveness of Screening for Chronic Hepatitis B Infection” (Gilead Sciences Inc; $56,000). He served as a consultant for Savient Pharmaceuticals (∼$300). Dr Hylek has participated in a symposium sponsored by Boehringer Ingelheim, served on advisory boards (Bayer Healthcare Pharmaceuticals; Boehringer Ingelheim GmbH; Bristol-Myers Squibb; Daiichi-Sankyo, Inc; Johnson & Johnson; Merck and Co, Inc; Ortho-McNeil Pharmaceutical, Inc; and Pfizer Inc) for amounts totaling < $10,000 and participated at the steering committee level for several pharmaceutical-sponsored studies (ARISTOTLE trial sponsored by Bristol-Myers Squibb and Pfizer Inc [< $10,000] and ORBIT-AF Registry sponsored by Ortho-McNeil Pharmaceutical, Inc [< $10,000]). Dr Go has received research funding from the National Heart, Lung, and Blood Institute related to antithrombotic therapy in atrial fibrillation and was a site principal investigator for a clinical trial sponsored by Johnson & Johnson and Bayer Healthcare Pharmaceuticals. Dr Halperin has received consulting fees from the following pharmaceutical manufacturers for advisory activities involving the development of anticoagulant drugs, none of which are currently approved for clinical use in any indication in the United States: Astellas Pharma, US; Bayer AG HealthCare; Boehringer Ingelheim; Daiichi Sankyo; Johnson & Johnson; and Sanofi-Aventis. He has received honoraria from Portola Pharmaceuticals, Inc as a member of the Data Safety Monitoring Board of its Phase II EXPLORE-AF trial involving an investigational anticoagulant for prevention of thromboembolism in patients with atrial fibrillation. He has received consulting fees from Biotronik, Inc as co-chair of the Steering Committee for the IMPACT clinical trial evaluating the use ambulatory monitoring technology in approved implanted cardiac arrhythmia devices to guide anticoagulation therapy for stroke prevention. He has received a consulting fee from the Bristol-Myers Squibb/Sanofi Partnership for advisory activities related to the use of the platelet inhibitor drug, clopidogrel, for prevention of thromboembolism in patients with atrial fibrillation. He has been a speaker at CME Symposia that derived partial funding from the following sponsors involved in the development of anticoagulants for potential use in patients with AF: Bayer AG HealthCare, Boehringer Ingelheim, and Sanofi-Aventis. Dr Lip has served as a consultant for Bayer, Astellas, Merck, Daiichi-Sankyo, AstraZeneca, Sanofi-Aventis, BMS/Pfizer, Biotronik, Portola, and Boehringer Ingelheim and has been on the speakers bureau for Bayer, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, and Sanofi-Aventis. Drs You, Howard, Fang, Schulman, Hughes, Manning, and Spencer have reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
Role of sponsors: The sponsors played no role in the development of these guidelines. Sponsoring organizations cannot recommend panelists or topics, nor are they allowed prepublication access to the manuscripts and recommendations. Guideline panel members, including the chair, and members of the Health & Science Policy Committee are blinded to the funding sources. Further details on the Conflict of Interest Policy are available online at http://chestnet.org.
Other contributions: We thank Louis Kuritzky, MD, for sharing his perspective as a frontline clinician during the development of our recommendations.
Endorsements: This guideline is endorsed by the American Association for Clinical Chemistry, the American College of Clinical Pharmacy, the American Society of Health-System Pharmacists, the American Society of Hematology, and the International Society of Thrombosis and Hematosis.
Additional information: The supplement Tables can be found in the Online Data Supplement at http://chestjournal.chestpubs.org/content/141/2_suppl/e531S/suppl/DC1.
Funding/Support: The Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines received support from the National Heart, Lung, and Blood Institute [R13 HL104758] and Bayer Schering Pharma AG. Support in the form of educational grants was also provided by Bristol-Myers Squibb; Pfizer, Inc; Canyon Pharmaceuticals; and sanofi-aventis US.
Disclaimer: American College of Chest Physician guidelines are intended for general information only, are not medical advice, and do not replace professional medical care and physician advice, which always should be sought for any medical condition. The complete disclaimer for this guideline can be accessed at http://chestjournal.chestpubs.org/content/141/2_suppl/1S.
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