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DOI: 10.1161/CIR.0b013e31820f14c0
published online Feb 14, 2011; Circulation
Richard L. Page, David J. Slotwiner, William G. Stevenson and Cynthia M. Tracy
Michael D. Ezekowitz, Warren M. Jackman, Craig T. January, James E. Lowe,
L. Samuel Wann, Anne B. Curtis, Kenneth A. Ellenbogen, N.A. Mark Estes, III,
Guidelines
Cardiology Foundation/American Heart Association Task Force on Practice
Atrial Fibrillation (Update on Dabigatran): A Report of the American College of
2011 ACCF/AHA/HRS Focused Update on the Management of Patients With
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ACCF/AHA/HRS Focused Update
2011 ACCF/AHA/HRS Focused Update on the Management
of Patients With Atrial Fibrillation (Update on Dabigatran)
A Report of the American College of Cardiology Foundation/American
Heart Association Task Force on Practice Guidelines
2011 WRITING GROUP MEMBERS
L. Samuel Wann, MD, MACC, FAHA, Chair*; Anne B. Curtis, MD, FACC, FAHA*;
Kenneth A. Ellenbogen, MD, FACC, FHRS†; N.A. Mark Estes III, MD, FACC, FHRS‡§;
Michael D. Ezekowitz, MB, ChB, FACC*§; Warren M. Jackman, MD, FACC, FHRS*;
Craig T. January, MD, PhD, FACC*; James E. Lowe, MD, FACC*;
Richard L. Page, MD, FACC, FHRS, FAHA†; David J. Slotwiner, MD, FACC†§;
William G. Stevenson, MD, FACC, FAHA�; Cynthia M. Tracy, MD, FACC*
2006 WRITING COMMITTEE MEMBERS
Valentin Fuster, MD, PhD, FACC, FAHA, FESC, Co-Chair;
Lars E. Ryde´n, MD, PhD, FACC, FESC, FAHA, Co-Chair; David S. Cannom, MD, FACC;
Harry J. Crijns, MD, FACC, FESC; Anne B. Curtis, MD, FACC, FAHA;
Kenneth A. Ellenbogen, MD, FACC, FHRS†; Jonathan L. Halperin, MD, FACC, FAHA;
G. Neal Kay, MD, FACC; Jean-Yves Le Heuzey, MD, FESC; James E. Lowe, MD, FACC;
S. Bertil Olsson, MD, PhD, FESC; Eric N. Prystowsky, MD, FACC; Juan Luis Tamargo, MD, FESC;
L. Samuel Wann, MD, MACC, FAHA, FESC
ACCF/AHA TASK FORCE MEMBERS
Alice K. Jacobs, MD, FACC, FAHA, Chair; Jeffrey L. Anderson, MD, FACC, FAHA, Chair-Elect;
Nancy Albert, PhD, CCNS, CCRN, FAHA; Mark A. Creager, MD, FACC, FAHA;
Steven M. Ettinger, MD, FACC; Robert A. Guyton, MD, FACC;
Jonathan L. Halperin, MD, FACC, FAHA; Judith S. Hochman, MD, FACC, FAHA;
Frederick G. Kushner, MD, FACC, FAHA; Erik Magnus Ohman, MD, FACC;
William G. Stevenson, MD, FACC, FAHA; Clyde W. Yancy, MD, FACC, FAHA
*ACCF/AHA Representative.
†HRS Representative.
‡ACCF/AHA Task Force on Performance Measures Representative.
§Recused from voting on Section 8.1.4.2.5, Recommendation for Use of Oral Direct Thrombin Inhibitor Anticoagulant Agents.
�ACCF/AHA Task Force on Practice Guidelines Liaison.
This document was approved by the American College of Cardiology Foundation Board of Trustees, the American Heart Association Science Advisory
and Coordinating Committee, and the Heart Rhythm Society in January 2011.
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/10.1161/CIR.0b013e31820f14c0/DC1.
The American Heart Association requests that this document be cited as follows: Wann LS, Curtis AB, Ellenbogen KA, Estes NAM 3rd, Ezekowitz
MD, Jackman WM, January CT, Lowe JE, Page RL, Slotwiner DJ, Stevenson WG, Tracy CM, writing on behalf of the 2006 ACC/AHA/ESC Guidelines
for the Management of Patients With Atrial Fibrillation Writing Committee. 2011 ACCF/AHA/HRS focused update on the management of patients with
atrial fibrillation (update on dabigatran): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice
Guidelines. Circulation. 2011;123:●●●–●●●.
This article is copublished in the Journal of the American College of Cardiology and HeartRhythm.
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(Circulation. 2011;123:00-00.)
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Circulation is available at http://circ.ahajournals.org DOI: 10.1161/CIR.0b013e31820f14c0
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Table of Contents
Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .000
1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .000
1.1. Methodology and Evidence Review . . . . . . . . . .000
1.2. Organization of the Writing Committee. . . . . . . .000
1.3. Document Review and Approval. . . . . . . . . . . . .000
8. Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .000
8.1.4.2.5. Recommendation for Use of Oral
Direct Thrombin Inhibitor
Anticoagulant Agents . . . . . . . . . . . . . . . .000
References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .000
Appendix 1. Author Relationships With Industry
and Other Entities . . . . . . . . . . . . . . . . . . .000
Appendix 2. Reviewer Relationships With Industry
and Other Entities . . . . . . . . . . . . . . . . . . .000
Preamble
A primary challenge in the development of clinical practice guide-
lines is keeping pace with the stream of new data on which
recommendations are based. In an effort to respond promptly to
new evidence, the American College of Cardiology Foundation/
American Heart Association (ACCF/AHA) Task Force on Practice
Guidelines (Task Force) has created a “focused update” process to
revise the existing guideline recommendations that are affected by
the evolving data or opinion. Before the initiation of this focused
approach, periodic updates and revisions of existing guidelines
required up to 3 years to complete. Now, however, new evidence
will be reviewed in an ongoing fashion to more efficiently respond
to important science and treatment trends that could have a major
impact on patient outcomes and quality of care. Evidence will be
reviewed at least twice a year, and updates will be initiated on an
as-needed basis and completed as quickly as possible while main-
taining the rigorous methodology that the ACCF and AHA have
developed during their partnership of more than 20 years.
These updated guideline recommendations reflect a consen-
sus of expert opinion after a thorough review primarily of
late-breaking clinical trials identified through a broad-based
vetting process as being important to the relevant patient
population, as well as other new data deemed to have an impact
on patient care (see Section 1.1, Methodology and Evidence
Review, for details). This focused update is not intended to
represent an update based on a full literature review from the
date of the previous guideline publication. Specific criteria/
considerations for inclusion of new data include the following:
● publication in a peer-reviewed journal;
● large, randomized, placebo-controlled trial(s);
● nonrandomized data deemed important on the basis of
results affecting current safety and efficacy assumptions;
● strength/weakness of research methodology and findings;
● likelihood of additional studies influencing current findings;
● impact on current and/or likelihood of need to develop new
performance measure(s);
● request(s) and requirement(s) for review and update from the
practice community, key stakeholders, and other sources free
of relationships with industry or other potential bias;
● number of previous trials showing consistent results; and
● need for consistency with a new guideline or guideline
revisions.
In analyzing the data and developing the recommendations
and supporting text, the focused update writing group used
evidence-based methodologies developed by the Task Force
that are described elsewhere.1 The committee reviewed and
ranked evidence supporting current recommendations with
the weight of evidence ranked as Level A if the data were
derived from multiple randomized clinical trials or meta-anal-
yses. The committee ranked available evidence as Level B
when data were derived from a single randomized trial or
nonrandomized studies. Evidence was ranked as Level C
when the primary source of the recommendation was consen-
sus opinion, case studies, or standard of care. In the narrative
portions of these guidelines, evidence is generally presented
in chronological order of development. Studies are identified
as observational, retrospective, prospective, or randomized
when appropriate. For certain conditions for which inade-
quate data are available, recommendations are based on
expert consensus and clinical experience and ranked as Level
C. An example is the use of penicillin for pneumococcal
pneumonia, for which there are no randomized trials and
treatment is based on clinical experience. When recommen-
dations at Level C are supported by historical clinical data,
appropriate references (including clinical reviews) are cited if
available. For issues where sparse data are available, a survey
of current practice among the clinicians on the writing
committee was the basis for Level C recommendations and
no references are cited. The schema for classification of
recommendation and level of evidence is summarized in
Table 1, which also illustrates how the grading system
provides an estimate of the size and the certainty of the
treatment effect. A new addition to the ACCF/AHA method-
ology is a separation of the Class III recommendations to
delineate whether the recommendation is determined to be of
“no benefit” or associated with “harm” to the patient. In
addition, in view of the increasing number of comparative
effectiveness studies, comparator verbs and suggested
phrases for writing recommendations for the comparative
effectiveness of one treatment/strategy with respect to an-
other for Class I and IIa, Level A or B only have been added.
The Task Force makes every effort to avoid actual, potential,
or perceived conflicts of interest that may arise as a result of
relationships with industry and other entities (RWI) among the
writing group. Specifically, all members of the writing group, as
well as peer reviewers of the document, are asked to disclose all
current relationships and those existing 12 months before initi-
ation of the writing effort. In response to implementation of a
newly revised RWI policy approved by the ACC and AHA, it is
also required that the writing group chair plus a majority of the
writing group (50%) have no relevant RWI. All guideline
recommendations require a confidential vote by the writing
group and must be approved by a consensus of the members
voting. Members who were recused from voting are noted on the
title page of this document and in Appendix 1. Members must
recuse themselves from voting on any recommendation to which
their RWI apply. Any writing group member who develops a
new RWI during his or her tenure is required to notify guideline
2 Circulation March 15, 2011
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staff in writing. These statements are reviewed by the Task Force
and all members during each conference call and/or meeting of
the writing group and are updated as changes occur. For detailed
information about guideline policies and procedures, please refer
to the ACCF/AHA methodology and policies manual.1 Authors’
and peer reviewers’ RWI pertinent to this guideline are disclosed
in Appendixes 1 and 2, respectively. In addition, to ensure
complete transparency, writing group members’ comprehensive
disclosure information—including RWI not pertinent to this
document—is available online as a supplement to this document.
Disclosure information for the Task Force is also available
online at www.cardiosource.org/ACC/About-ACC/Leadership/
Guidelines-and-Documents-Task-Forces.aspx. The work of the
writing group was supported exclusively by the ACCF and AHA
and Heart Rhythm Society (HRS) without commercial support.
Writing group members volunteered their time for this effort.
The ACCF/AHA practice guidelines address patient populations
(and healthcare providers) residing in North America. As such,
drugs that are currently unavailable in North America are discussed
in the text without a specific classification of recommendation. For
studies performed in large numbers of subjects outside of North
America, each writing group reviews the potential impact of
different practice patterns and patient populations on the treatment
effect and the relevance to the ACCF/AHA target population to
determine whether the findings should inform a specific
recommendation.
Table 1. Applying Classification of Recommendations and Level of Evidence
* Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior
myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak.
Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a
very clear clinical consensus that a particular test or therapy is useful or effective.
†For comparative effectiveness recommendations (Class I and IIa; Level of Evidence: A and B only), studies that support the use of comparator verbs should involve
direct comparisons of the treatments or strategies being evaluated.
Wann et al Atrial Fibrillation Focused Update: Dabigatran 3
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The ACCF/AHA practice guidelines are intended to assist
healthcare providers in clinical decision making by describing a
range of generally acceptable approaches for the diagnosis, man-
agement, and prevention of specific diseases or conditions. These
practice guidelines represent a consensus of expert opinion after a
thorough review of the available current scientific evidence and are
intended to improve patient care. The guidelines attempt to define
practices that meet the needs of most patients in most circum-
stances. The ultimate judgment regarding care of a particular patient
must be made by the healthcare provider and patient in light of all
the circumstances presented by that patient. Thus, there are circum-
stances in which deviations from these guidelines may be appropri-
ate. Clinical decision making should consider the quality and
availability of expertise in the area where care is provided. When
these guidelines are used as the basis for regulatory or payer
decisions, the goal should be improvement in quality of care. The
Task Force recognizes that situations arise for which additional data
are needed to better inform patient care; these areas will be
identified within each respective guideline when appropriate.
Prescribed courses of treatment in accordance with these
recommendations are effective only if they are followed. Be-
cause lack of patient understanding and adherence may ad-
versely affect outcomes, physicians and other healthcare provid-
ers should make every effort to engage the patient’s active
participation in prescribed medical regimens and lifestyles.
The recommendations in this focused update will be considered
current until they are superseded by another focused update or the
full-text guideline is revised. This focused update is published in the
Journal of the American College of Cardiology, Circulation, and
HeartRhythm as an update to the full-text guideline, and it is also
available on the ACC (www.cardiosource.org), AHA
(my.americanheart.org), and HRS (www.hrsonline.org) World
Wide Web sites. A revised version of the full-text guideline with
links to the focused update is e-published in the March 15, 2011,
issues of the Journal of the American College of Cardiology and
Circulation. For easy reference, this online-only version denotes
sections that have been updated.
Alice K. Jacobs, MD, FACC, FAHA
Chair, ACCF/AHA Task Force on Practice Guidelines
1. Introduction
1.1. Methodology and Evidence Review
The publication of the RE-LY (Randomized Evaluation of Long-
Term Anticoagulation Therapy) trial was considered important
enough to prompt a focused update of the ACC/AHA/ESC 2006
Guidelines for the Management of Patients With Atrial Fibrillation.2
To provide clinicians with a comprehensive set of data, whenever
deemed appropriate or when published, the absolute risk difference
and number needed to treat or harm will be provided in the
guideline, along with confidence intervals (CI) and data related to
the relative treatment effects such as odds ratio, relative risk (RR),
hazard ratio, or incidence rate ratio.
Consult the full-text version or executive summary of the
ACC/AHA/ESC 2006 Guidelines for the Management of
Patients With Atrial Fibrillation for policy on clinical areas
not covered by the focused update.2 The individual recom-
mendations in this focused update will be incorporated into
future revisions and/or updates of the full-text guideline.
1.2. Organization of the Writing Committee
For this focused update, all eligible members of the 2006
Atrial Fibrillation Writing Committee were invited to partic-
ipate; those who agreed (referred to as the 2011 focused
update writing group) were required to disclose all RWI
relevant to the data under consideration. The HRS was invited
to be a partner on this update and provided 3 representatives.
1.3. Document Review and Approval
This document was reviewed by 2 official reviewers each
nominated by the ACCF, AHA, and HRS and 5 individual
content reviewers (including members of the ACCF Electro-
physiology Committee, the ACCF/AHA Task Force on Per-
formance Measures, and the ACCF/AHA Atrial Fibrillation
Data Standards Committee). All information on reviewers’
RWI was collected and distributed to the writing committee
and is published in this report (Appendix 2).
This document was approved for publication by the gov-
erning bodies of the ACCF, AHA, and HRS.
8. Management
This guideline update focuses on the use of dabigatran, a new
antithrombotic agent that was recently approved by the US
Food and Drug Administration (FDA), for the management of
patients with atrial fibrillation (AF).
8.1.4.2.5. Recommendation for Use of Oral Direct
Thrombin Inhibitor Anticoagulant Agents
(See Table 2).
Dabigatra