This is the current release of the guideline.

This guideline is updates a previous version: Singer DE, Albers GW, Dalen JE, Go AS, Halperin JL, Manning WJ. Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004 Sep;126(3 Suppl):429S-56S.

Atrial fibrillation

Note: Atrial fibrillation (AF) is the most common significant cardiac rhythm disorder and is an important independent risk factor for ischemic stroke.

Management
Prevention
Risk Assessment
Treatment

Cardiology
Critical Care
Emergency Medicine
Family Practice
Internal Medicine

Advanced Practice Nurses
Allied Health Personnel
Health Care Providers
Nurses
Patients
Physicians
Psychologists/Non-physician Behavioral Health Clinicians
Social Workers

• To discuss antithrombotic therapy for patients with atrial fibrillation (AF)
• To update evidence-based recommendations for the use of antithrombotic and thrombolytic therapy for the management of thromboembolic conditions

Patients with atrial fibrillation (AF)

1. Assessment of risk factors
2. Oral vitamin K antagonist (VKA), warfarin
3. Aspirin
4. Monitoring international normalized ratio (INR) and partial thromboplastin time (PTT)
5. Transesophageal echocardiography (TEE)-guided and non–TEE-guided cardioversion
6. Anticoagulation for elective cardioversion (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH])
7. Antithrombotic management of atrial flutter
8. Repeat TEE before attempting additional cardioversion
9. Management of AF in specific populations

• Target international normalized ratio
• Mortality
• Recurrent episodes of atrial fibrillation
• Atrial flutter

Hand-searches of Published Literature (Primary Sources)
Searches of Electronic Databases

Process of Searching for Evidence

Defining the clinical question provided the framework for formulating eligibility criteria that guided the search for relevant evidence. In specifying eligibility criteria, authors identified not only patients, interventions, and outcomes, but also methodologic criteria. For many recommendations, authors restricted eligibility to randomized controlled trials (RCTs).

For many questions, randomized trials did not provide sufficient data, and chapter authors included observational studies when randomized trials were not the most appropriate design to address the research question. In particular, randomized trials are not necessarily the best design to understand risk groups, that is, the baseline or expected risk of a given event for certain subpopulations. Because no interventions are typically examined in questions about prognosis, one replaces interventions by the duration of exposure measured in time.

Identifying the Evidence

To identify the relevant evidence, a team of librarians and research associates at the McMaster University Evidence based practice center (EPC) conducted comprehensive literature searches. Methodologic experts (including the editors) and the EPC librarians reviewed each question to ensure the development of a comprehensive search strategy. For example, for questions about antiplatelet agents, the EPC consulted chapter authors to ensure that the search included all relevant antiplatelet agents. More specifically, authors then decided whether to include dipyridamole in a search that already included aspirin, clopidogrel, and ticlopidine.

For each question the authors provided, the librarians searched the Cochrane Database of Systematic Reviews, MEDLINE, and Embase for published English-language literature and human studies between 2002 and May 2006. To filter MEDLINE and Embase search results for RCT evidence, the librarians used the search strategy developed by the Cochrane Collaboration. These searches updated the more comprehensive and sensitive searches conducted for the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy: Evidence Based Guidelines.

The EPC team conducted separate searches for systematic reviews; RCTs; and, if applicable, observational studies. For observational studies, searches were not restricted in terms of methodology. Although increasing the probability of identifying all published studies, this sensitive approach resulted in large numbers of citations for many of the defined clinical questions. Therefore, trained research assistants screened the citation list developed from the search using criteria of increased specificity to reduce the number of irrelevant citations that the authors received. These irrelevant citations included press news, editorials, narrative reviews, single-case reports, studies that included fewer participants than specified by authors as an inclusion criterion, animal studies (any nonhuman studies), and letters to the editor. Authors did not include data from abstracts of meetings for the development of recommendations, and the guideline developers did not explicitly use Internet sources to search for research data. Authors were encouraged, however, to mention abstracts that reported on groundbreaking data that were particularly relevant to a specific question in the chapters in order to alert readers that new, fully published evidence might become available shortly.

Standard Consideration of Study Quality

High-quality clinical guidelines should pay careful attention to the methodologic quality of the studies that form the basis of their recommendations. Using the example of the prevention of venous thromboembolism during air travel, Table 1 in the methodology companion (see "Availability of Companion Documents" field) shows the criteria for assessment of study quality (randomization, concealment or treatment allocation, blinding, completeness of follow-up, and whether the analysis was performed according to the intention-to-treat principle), and Table 2 in the methodology companion (see "Availability of Companion Documents" field) shows the presentation of results that were circulated to the authors. Whereas all authors attended to these criteria, the guideline developers have summarized the results of the quality assessment for only a minority of the recommendations. Readers can find these summaries in an online appendix to the recommendations (see online supplemental data).

In assessing the quality of observational studies, the guideline developers did not make a distinction between prospective and retrospective because the key issues are unbiased sampling, high-quality measurement of patient characteristics and outcomes, and complete follow-up.

Although it is more likely that these quality criteria will be achieved in prospective studies, prospective studies may fail to achieve them, and retrospective studies may succeed. The guideline developers did make a key distinction about whether internal comparisons exist and their nature. Studies without internal comparisons received the label "case series" unless they met the following criteria: (1) a protocol existed before the date of commencement of data collection; (2) a definition of inclusion and exclusion criteria was available; (3) the study reported the number of excluded patients; (4) the study conducted a standardized follow-up, including description of schedule of follow-up, investigation of suspected outcomes, and criteria used to define outcomes; and (5) the study reported all losses to follow-up.

The guideline developers labeled studies that met these criteria "cohort studies without internal controls." Studies with internal comparisons received the label "cohort studies with concurrent controls" or "cohort studies with historical controls." These cohort studies may succeed or fail to ensure settings, similar time frames, adjustment for differences in patients' characteristics, and follow-up with patients. These features were captured in descriptive tables provided to authors when requested from the EPC.

Not stated

Weighting According to a Rating Scheme (Scheme Given)

The rating scheme framework captures the trade-off between benefits and risks (1 or 2) and the methodological quality of the underlying evidence (A, B, or C). See "Grades of recommendations for antithrombotic agents" in the "Availability of Companion Documents" field and the "Rating Scheme for the Strength of the Recommendations." field.

Review of Published Meta-Analyses
Systematic Review with Evidence Tables

Summarizing Evidence

The electronic searches also included searches for systematic reviews. If authors were satisfied with a recent high-quality systematic review, evidence from that review provided a foundation for the relevant recommendation.

Pooled analyses from high-quality systematic reviews formed summary data on which panelists based their recommendations wherever possible. Pooling offers the advantage of obtaining more precise estimates of treatment effects and allows for greater generalizability of results. However, pooling also bears the risk of spurious generalization. In general, the summary estimates of interest were the different types of outcomes conveying benefits and downsides (risk, burden, and cost). When pooled estimates of effects were not available, the McMaster University Evidence based practice center (EPC) conducted meta-analysis to obtain pooled estimates for specific questions. These were questions that authors had specifically identified.

Expert Consensus (Consensus Development Conference)

Group-Specific Recommendations

In general, the guideline developers have endeavored to make their recommendations as specific as possible for patient subgroups differing according to risk. Whenever valid prognostic data were available, the guideline developers used them to estimate absolute effects and made recommendations accordingly. Unfortunately, reliable prognostic indexes are not usually available, limiting the extent to which such group-specific recommendations are possible.

Acknowledge Values and Preferences and Resource Use Underlying Recommendations

Under ideal circumstances, knowledge of average patient values and preferences would be available for every recommendation, the panel members would summarize these values and preferences, and they would be integrated into the recommendations that guideline developers make. The guideline developers asked all chapter chairs before beginning the searches for the relevant literature to identify recommendations that they believed were particularly sensitive to patients' values and preferences. Moderate-quality evidence regarding values and preferences bearing directly on the recommendations proved available for only the chapter that addresses antithrombotic therapy in patients with atrial fibrillation. The panelists bore in mind what average patient values and preferences may be; the process, however, is speculative.

The guideline developer's main strategy for dealing with this unsatisfactory situation is to make the values and preferences underlying the recommendations explicit whenever the panelists believed that value and preference issues were crucial for a recommendation.

In addition, the guideline developers involved three consultants with expertise in the area of values and preferences to collaborate with the chairs of two chapters and try to ensure that the guidelines adequately represented the views of patients. This collaboration led to extensive discussions among the chapter authors and the consultants and the reflection of these discussions in the associated values and preference statements.

Finalizing and Harmonizing Recommendations

After having completed the steps the guideline developers have described above, the guideline authors formulated draft recommendations before the conference, which laid the foundation for authors to work together and critique the recommendations. Figure 1 in the methodology companion (see "Availability of Companion Documents" field) shows the process of guideline development and review. Drafts of chapters that included draft recommendations were usually distributed for peer review to at least two panel members and were always reviewed by at least one panel editor before the conference. Written critiques were prepared and returned to the authors for revision of their work. At the plenary conference, a representative of each chapter presented potentially controversial issues in their recommendations. Chapter authors met to integrate feedback and consider related recommendations in other chapters and to revise their own guidelines accordingly. Authors continued this process after the conference until they reached agreement within their groups and with other author groups who provided critical feedback. The editors of this supplement harmonized the chapters and resolved remaining disagreements between chapters through facilitated discussion. All major correspondence and discussions at the meeting were recorded in written and audio protocols and are publicly available.

*The guideline developers use the wording recommend for strong (Grade 1) recommendations and suggest for weak (Grade 2) recommendations.

For these guidelines, the guideline developers implemented recommendations of a recent American College of Chest Physicians (ACCP) task force on integrating resource allocation in clinical practice guidelines by restricting resource expenditure consideration to a small number of recommendations for which they were particularly relevant. The guideline developers relied on two consultants with expertise in economic assessment to help with the process of considering costs in those small numbers of recommendations that the guideline developers considered very important to the decision.

Recommendations highly sensitive to resource allocation now include value and preference statements regarding how cost issues were integrated.

Refer to "Strategies for incorporating resource allocation and economic considerations" (see "Availability of Companion Documents" field) for details of the cost analyses.

External Peer Review
Internal Peer Review

The American College of Chest Physicians (ACCP) Health Science Policy (HSP) established a process for the thorough review of all ACCP evidence-based clinical practice guidelines. After final review by the editors, the guidelines underwent review by appropriate NetWorks of the ACCP (for these guidelines, the Cardiovascular and Pulmonary Vascular NetWorks), the HSP, and the Board of Regents. The latter two have the right of approval or disapproval but usually work with the guideline authors and editors to make necessary revisions before final approval. Each group identified primary reviewers who read the full set of chapters as well as individual committee members who were responsible for reviewing one or more chapters. The reviewers considered both content and methodology as well as whether there was balanced, not biased, reporting and adherence to HSP processes. Finally, the CHEST editor-in-chief read and forwarded the manuscripts for nonbiased, independent, external peer review before acceptance for publication.

None provided

The type of supporting evidence is identified and graded for each recommendation (see "Major Recommendations").

Effective use of antithrombotic/anticoagulant therapy to treat and prevent atrial fibrillation

• Intracranial hemorrhage (ICH) is the only hemorrhagic complication that regularly produces deficits as great as or greater than the ischemic strokes antithrombotic therapy is designed to prevent.
• Systemic embolism is the most serious complication of cardioversion and may follow external or internal direct current (DC), pharmacologic, and spontaneous cardioversion of atrial fibrillation (AF).

Limitations of These Guideline Development Methods

Limitations of these guidelines include the limited quantity and quality of available studies for some patient groups. Second, it is possible that some authors followed this methodology more closely than others, although the development process was centralized by an evidence-based practice center (EPC) and supervised by the editors. Third, it is possible that the guideline developers missed relevant studies in spite of the comprehensive searching process. Fourth, despite their efforts to begin centralizing the methodologic evaluation of all studies to facilitate uniformity in the validity assessments of the research incorporated into these guidelines, resources were insufficient to conduct this evaluation for all but a few of the recommendations in each chapter. Fifth, the guideline developers performed only few statistical pooling exercises of primary study results. Finally, sparse data on patient preferences and values represent additional limitations inherent to most guideline development methods.

An implementation strategy includes local educational programs and tools offered through the American College of Chest Physicians (ACCP) Board of Governors and select other locations. The Veterans Administration (VA) will also participate in a pilot project.

Living with Illness
Staying Healthy

Effectiveness

Not applicable: The guideline was not adapted from another source.

2001 Jan (revised 2008 Jun)

American College of Chest Physicians - Medical Specialty Society

American College of Chest Physicians

American College of Chest Physicians (ACCP) Expert Panel on Antithrombotic and Thrombolytic Therapy

Primary Authors: 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

Committee Co-Chairs: Jack Hirsh, MD, FCCP (Chair); Gordon H. Guyatt, MD, FCCP; Gregory W. Albers, MD; Robert A. Harrington, MD, FCCP; Holger J. Schünemann, MD, PhD, FCCP

Participants: Giancarlo Agnelli, MD; Pierre Amarenco, MD; Jack E. Ansell, MD; Collin Baigent; Shannon M. Bates, MD; Kenneth A. Bauer, MD; Richard C. Becker, MD; Peter B. Berger, MD; David Bergqvist, MD, PhD; Rebecca J. Beyth, MD; Christopher P. Cannon, MD; Elizabeth A. Chalmers, MB, ChB, MD; Anthony K.C. Chan, MBBS; Clifford W. Colwell, Jr., MD; Anthony J. Comerota, MD; Deborah Cook, MD; Mark A. Crowther, MD; James E. Dalen, MD; Gabrielle deVeber, MD, MHSc; Maria Benedetta Donati, MD, PhD; James D. Douketis, MD; Andrew Dunn, MD; J. Donald Easton, MD; Michael Ezekowitz, MD; Margaret Fang; William H. Geerts, MD, FCCP; Alan S. Go, MD; Samuel Z. Goldhaber, MD, FCCP; Shaun D. Goodman, MD; Michael Gould, MD, FCCP; Ian A. Greer, MD; Andreas Greinacher, MD; David Gutterman, MD, FCCP, HSP; Jonathan L. Halperin, MD; John A. Heit, MD; Elaine M. Hylek, MD; Alan Jacobson, MD; Roman Jaeschke, MD, PhD; Amir K. Jaffer, MD; Susan Kahn; Clive Kearon, MBBCh, PhD; Fenella Kirkham, MBBC; Andreas Koster, MD, PhD; Michael R. Lassen, MD; Mark N. Levine, MD, MSc; Sandra Zelman Lewis, PhD; A. Michael Lincoff, MD; Gregory YH Lip, MD; Christopher Madias, MD; Warren J. Manning, MD; Daniel B. Mark, MD; M. Patricia Massicotte, MD, MSc; David Matchar, MD; Thomas W. Meade, DM, FCCP; Venu Menon, MD; Tracy Minichiello, MD; Paul Monagle, MBBS, MSc, MD, FCCP; Christopher M. O'Connor, MD; Patrick O'Gara, MD; E. Magnus Ohman, MD; Ingrid Pabinger, MD; Gualtiero Palareti, MD; Carlo Patrono, MD; Stephen G. Pauker, MD; Graham F. Pineo, MD; Jeffrey J. Popma, MD; Gary Raskob, PhD; Gerald Roth, MD; Ralph L. Sacco, MD; Deeb N. Salem, MD, FCCP; Charles-Marc Samama, MD, FCCP; Meyer Michel Samama, MD; Sam Schulman, MD, PhD; Daniel Singer, MD; Michael Sobel, MD; Shoshanna Sofaer, DrPH; Alex C. Spyropoulos, MD FCCP; Ph. Gabriel Steg, MD; Philip Teal, MD; Raymond Verhaeghe, MD; David A. Vorchheimer, MD; Theodore E. Warkentin, MD; Jeffrey Weitz, MD

Dr. Singer discloses that he has received grant monies from the US Public Health Service (research grant No. AB15478), the National Institute on Aging, the National Institutes of Health, and the Eliot B. and Edith C. Shoolman Fund of the Massachusetts General Hospital. He has served as a consultant to Medtronic, Boehringer Ingelheim, Bayer HealthCare, Johnson & Johnson, Sanofi-Aventis, and Daiichi Sankyo Inc.

Dr. Albers discloses that he has received grant monies from the National Institutes of Health, Astra, Genentech, Bristol-Myers Squibb, Sanofi, Boehringer Ingelheim, NMT Medical, and Aventis. He is also on the speakers bureau for Boehringer Ingelheim, and advisory committees for Astra, Aventis, Boehringer Ingelheim, NMT Medical, Bristol-Myers Squibb, and Sanofi.

Dr. Dalen reveals no real or potential conflicts of interest or commitment.

Dr. Fang reveals no real or potential conflicts of interest or commitment.

Dr. Go reveals no real or potential conflicts of interest or commitment.

Dr. Halperin discloses that he has received consulting fees from Astellas Pharma, Bayer AG Healthcare, Boehringer Ingelheim, Daiichi Sankyo Pharma, GlaxoSmithKline, Johnson & Johnson, and Sanofi-Aventis.

Dr. Manning reveals no real or potential conflicts of interest or commitment.

Professor Lip discloses that he has received grant monies from the British Heart Foundation, Sanofi, and AstraZeneca. He is also on the speaker bureaus for AstraZeneca and Bayer, and has served on an advisory committee for AstraZeneca, Daiichi Sankyo, Bayer, and Astellas.

American College of Clinical Pharmacy - Medical Specialty Society
American Society of Health-System Pharmacists - Professional Association

This is the current release of the guideline.

This guideline is updates a previous version: Singer DE, Albers GW, Dalen JE, Go AS, Halperin JL, Manning WJ. Antithrombotic therapy in atrial fibrillation: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004 Sep;126(3 Suppl):429S-56S.

None available

This summary was completed by ECRI on July 30, 2001. The information was verified by the guideline developer as of October 31, 2001. This NGC summary was updated by ECRI on December 8, 2004. The updated information was verified by the guideline developer on January 12, 2005. This summary was updated by ECRI on March 6, 2007 following the U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin sodium). This summary was updated by ECRI Institute on June 22, 2007 following the U.S. Food and Drug Administration (FDA) advisory on heparin sodium injection. This summary was updated by ECRI Institute on September 7, 2007 following the revised U.S. Food and Drug Administration (FDA) advisory on Coumadin (warfarin). This summary was updated by ECRI Institute on March 14, 2008 following the updated FDA advisory on heparin sodium injection. This NGC summary was updated by ECRI Institute on November 26, 2008. The updated information was verified by the guideline developer on January 7, 2009.

This NGC summary is based on the original guideline, which is subject to the guideline developer's copyright restrictions.