2011 ACCF/AHA/HRS Focused Update on the Management of Patients with Atrial Fibrillation (updating the 2006 Guideline)

HomeCirculationVol. 123, No. 12011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline) Free AccessResearch ArticlePDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessResearch ArticlePDF/EPUB2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline)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, Anne B. Curtis, MD, FACC, FAHA, Craig T. January, MD, PhD, FACC, Kenneth A. Ellenbogen, MD, FACC, FHRS, James E. Lowe, MD, FACC, N.A. Mark EstesIII, MD, FACC, FHRS, Richard L. Page, MD, FACC, FHRS, Michael D. Ezekowitz, MB, ChB, FACC, David J. Slotwiner, MD, FACC, Warren M. Jackman, MD, FACC, FHRS, William G. Stevenson, MD, FACC, FAHA and Cynthia M. Tracy, MD, FACC 2011 Writing Group Members , L. Samuel WannL. Samuel Wann , Anne B. CurtisAnne B. Curtis , Craig T. JanuaryCraig T. January , Kenneth A. EllenbogenKenneth A. Ellenbogen , James E. LoweJames E. Lowe , N.A. Mark EstesIIIN.A. Mark EstesIII , Richard L. PageRichard L. Page , Michael D. EzekowitzMichael D. Ezekowitz , David J. SlotwinerDavid J. Slotwiner , Warren M. JackmanWarren M. Jackman , William G. StevensonWilliam G. Stevenson and Cynthia M. TracyCynthia M. Tracy Originally published20 Dec 2010https://doi.org/10.1161/CIR.0b013e3181fa3cf4Circulation. 2011;123:104–123is corrected byCorrectionOther version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2010: Previous Version 1 Jacobs Alice K., MD, FACC, FAHAPreambleA primary challenge in the development of clinical practice guidelines 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 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 maintaining the rigorous methodology that the ACCF and AHA have developed during their partnership of more than 20 years.These updated guideline recommendations reflect a consensus 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; andneed for consistency with a new guideline or guideline revisions.In analyzing the data and developing updated recommendations and supporting text, the focused update writing group used evidence-based methodologies developed by the ACCF/AHA Task Force on Practice Guidelines that are described elsewhere.1 The Task Force on Practice Guidelines makes every effort to avoid actual, potential, or perceived conflicts of interest that may arise as a result of industry relationships or personal interests among the writing group. Specifically, all members of the writing group, as well as peer reviewers of the document, are asked to disclose ALL relevant relationships and those existing 12 months before initiation of the writing effort. In response to implementation of a new relationship with industry and other entities (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 members before and after external review of the document 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 recommendations to which their RWI apply. Any writing group member who develops a new RWI during his or her tenure is required to notify guideline staff in writing. These statements are reviewed by the Task Force on Practice Guidelines 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. Additionally, to ensure complete transparency, writing group members' comprehensive disclosure information—including RWI not pertinent to this document—are available online as a data supplement. Disclosure information for the ACCF/AHA Task Force on Practice Guidelines is available online at www.cardiosource.org/ACC/About-ACC/Leadership/Guidelines-and-Documents-Task-Forces.aspx and at www.americanheart.org/presenter.html?identifier=3039684. Writing committee members who chose not to participate are not listed as authors of this focused update. The work of the writing group was supported exclusively by the ACCF and AHA without commercial support. Writing group members volunteered their time for this effort.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-analyses. 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 consensus opinion of experts, 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 where appropriate. For certain conditions for which inadequate 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, where there are no randomized trials and treatment is based on clinical experience. When recommendations 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 Recommendations (COR) and Level of Evidence (LOE) is summarized inTable 1, which also illustrates how the grading system provides an estimate of the size of the treatment effect and an estimate of the certainty of the treatment effect. A new addition to the ACCF/AHA methodology 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 another for COR I and IIa, LOE A or B only have been added.Table 1. Applying Classification of Recommendation and Level of EvidenceTable 1. Applying Classification of Recommendation and Level of Evidence*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, 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. Even though randomized trials are not available, 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.The ACCF/AHA practice guidelines address patient populations (and healthcare providers) residing in North America. As such, drugs that are not currently available in North America are discussed in the text without a specific COR. 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.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, management, and prevention of specific diseases or conditions. The guidelines attempt to define practices that meet the needs of most patients in most circumstances. 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 circumstances in which deviations from these guidelines may be appropriate. Clinical decision making should consider the quality and availability of expertise in the area where care is provided.Prescribed courses of treatment in accordance with these recommendations are effective only if they are followed. Because lack of patient understanding and adherence may adversely affect treatment outcomes, physicians and other healthcare providers should make every effort to engage the patient's active participation in prescribed medical regimens and lifestyles. When these guidelines are used as the basis for regulatory or payer decisions, the goal should be improvement in quality of care aligned with the patient's best interest.With the exception of the recommendations presented here, the full-text guideline remains current. Only the recommendations from the affected section(s) of the full-text guideline are included in this focused update. For easy reference, all recommendations from any section of a guideline affected by a change are presented with notation as to whether they remain current, are new, or have been modified. When evidence affects recommendations in more than 1 set of guidelines, those guidelines are updated concurrently.The recommendations in this focused update will be considered current until they are superseded by another focused update or the full-text guidelines are revised. This focused update is published in the December 28, 2010/January 4, 2011, issue of the Journal of the American College of Cardiology, the January 4, 2011, issue of Circulation, and the December 2010 issue of HeartRhythm as an update to the full-text guideline,2 and it is available on the ACC (http://www.cardiosource.org), AHA (my.americanheart.org), and Heart Rhythm Society (hrsonline.org) World Wide Web sites.Alice K. Jacobs, MD, FACC, FAHA Chair, ACCF/AHA Task Force on Practice Guidelines1. Introduction1.1. Methodology and Evidence ReviewLate-breaking clinical trials presented at the 2009 annual scientific meetings of the ACC, AHA, and European Society of Cardiology (ESC), as well as selected other data reported through April 2010, were reviewed by the standing guideline writing committee along with the Task Force on Practice Guidelines and other experts to identify those trials and other key data that may impact guideline recommendations. On the basis of the criteria/considerations noted above, recent trial data and other clinical information were considered important enough to prompt a focused update of the ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation.2To provide clinicians with a comprehensive set of data, whenever deemed appropriate or when published in the article, data from the clinical trial will be used to calculate the absolute risk difference (ARD) and number needed to treat (NNT) or harm (NNH); data related to the relative treatment effects will also be provided, such as odds ratio (OR), relative risk (RR), hazard ratio (HR), or incidence rate ratio (IRR) along with confidence interval (CI) when available.Consult the full-text version or executive summary of the ACC/AHA/ESC 2006 Guidelines for the Management of Patients with Atrial Fibrillation2 for policy on clinical areas not covered by the focused update. The individual recommendations in this focused update will be incorporated into future revisions and/or updates of the full-text guideline.1.2. Organization of the Writing CommitteeFor this focused update, all members of the 2006 Atrial Fibrillation Writing Committee were invited to participate; 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 Heart Rhythm Society was invited to be a partner on this update and provided 3 representatives.1.3. Document Review and ApprovalThis document was reviewed by 2 official reviewers each nominated by the ACCF, the AHA, the Heart Rhythm Society, and 25 individual content reviewers (including members of the ACCF Electrophysiology Committee, the Atrial Fibrillation Performance Measures Committee, and the Atrial Fibrillation Data Standards Committee). All reviewer RWI information was collected and distributed to the writing committee and is published in this report (Appendix 2).This document was approved for publication by the governing bodies of the ACCF, AHA, and Heart Rhythm Society.8. ManagementThis guideline update focuses on several areas in which new data on management of patients with atrial fibrillation (AF) have become available, including a) recommendations for strict versus lenient heart rate control, b) combined use of antiplatelet and anticoagulant therapy, and c) use of dronedarone. Recommendations are not made for use of dabigatran, a new antithrombotic agent which was not approved by the US Food and Drug Administration (FDA) at the time of organizational approval of this document, or for the Watchman device for occlusion of the left atrial appendage which is investigational pending FDA approval.8.1.3. Rate Control During Atrial FibrillationCRITERIA FOR RATE CONTROL. In patients with AF, the ventricular rate may accelerate excessively during exercise even when it is well controlled at rest (Table 2). Rate reduction, allowing adequate time for ventricular filling and avoiding rate-related ischemia, may result in improved hemodynamics. Therefore, evaluating the heart rate response to submaximal or maximal exercise or to monitor the rate over an extended period (eg, by 24-hour Holter recording) may be an option. In addition, rate variability during AF provides information about the status of the autonomic nervous system that may have independent prognostic implications.4–7 Parameters for optimal rate control in AF remain controversial. The definition of adequate rate control has been based primarily on short-term hemodynamic benefits and has not been well studied with respect to regularity or irregularity of the ventricular response to AF, quality of life, symptoms, or development of cardiomyopathy. No standard method for assessment of heart rate control has been established to guide management of patients with AF. Criteria for rate control vary with patient age but usually involve achieving ventricular rates between 60 and 80 bpm at rest and between 90 and 115 bpm during moderate exercise. For the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) study, adequate control was defined as an average heart rate of up to 80 bpm at rest and either an average rate of up to 100 bpm over at least 18 hours of ambulatory Holter monitoring with no rate greater than 100% of the maximum age-adjusted predicted exercise heart rate or a maximum heart rate of 110 bpm during a 6-minute walk test.8Table 2. Recommendation for Rate Control During Atrial Fibrillation2011 Focused Update RecommendationCommentsClass III–No Benefit1. Treatment to achieve strict rate control of heart rate (<80 bpm at rest or <110 bpm during a 6-minute walk) is not beneficial compared to achieving a resting heart rate <110 bpm in patients with persistent AF who have stable ventricular function (left ventricular ejection fraction >0.40) and no or acceptable symptoms related to the arrhythmia, though uncontrolled tachycardia may over time be associated with a reversible decline in ventricular performance.3(Level of Evidence: B)New recommendationThe potential benefits of strict (resting heart rate <80 bpm, heart rate <110 bpm during moderate exercise) versus lenient (resting heart rate <110 bpm) rate control were addressed in the RACE II (Rate Control Efficacy in Permanent Atrial Fibrillation) trial of 614 patients with permanent AF.3 AF was treated with a variety of atrioventricular (AV) nodal blocking agents to control heart rate.3 Primary endpoints were death from cardiovascular causes, hospitalization for heart failure, stroke, systemic embolism, bleeding, and life-threatening arrhythmias. The 3-year estimated cumulative incidence of the primary outcome was 12.9% in the lenient-control group and 14.9% in the strict-control group (Appendix 3), with an absolute difference between lenient control and strict control of −2.0 percentage points (90% CI, −7.6 to 3.5; P<0.001) and HR of 0.84 (90% CI, 0.58 to 1.21; P=0.001 for the prespecified noninferiority margin). Symptoms were also similar in both groups. All patients included in the study were ambulatory and relatively young (mean age, 68 years), predominantly male, and may have been healthier and less symptomatic than many patients encountered in clinical practice. Long-term effects of a more rapid heart rate response to AF on ventricular function were not studied. If a lenient rate control strategy is chosen for patients with persistent AF who have stable ventricular function (left ventricular [LV] ejection fraction >0.40) and or no acceptable symptoms related to AF, LV function should be monitored.The RACE II study reported only a total of 81 composite events in 614 patients and was not adequately powered to make conclusive comments on whether there were or were not clinically relevant differences in clinical outcomes between strict- and lenient-rate control.3 Nevertheless, strict targeting of treatment to achieve an arbitrary heart rate seems unnecessary. The RACE II study shows that lenient-rate control <110 bpm is not inferior to strict-rate control <80 bpm. As lenient-rate control is generally more convenient, requiring fewer outpatient visits and examinations, lenient-rate control may be adopted as a reasonable strategy in patients with permanent AF.The Atrial Fibrillation and Congestive Heart Failure Trial compared the benefits of rhythm control with rate control in a randomized, multicenter trial of 1376 patients with AF and congestive heart failure.9 AF was defined as 1 episode of AF lasting at least 6 hours or requiring cardioversion within the preceding 6 months or an episode lasting for at least 10 minutes within the previous 6 months and previous cardioversion. Congestive heart failure was defined as an ejection fraction of ≤35% and symptomatic New York Heart Association (NYHA) class II or IV heart failure within the previous 6 months, or an ejection fraction of ≤25%. Rhythm control included cardioversion and antiarrhythmic therapy, primarily using amiodarone, repeat cardioversion if needed, and possible referral for nonpharmacologic therapy. Rate control was achieved primarily using beta blockers with digitalis to achieve a target heart rate of <80 bpm at rest or <110 bpm during a 6-minute walk test. No difference was found in the primary endpoint of death from cardiovascular causes with a mean follow-up of 37 months. One hundred eighty-two (27%) in the rhythm-control group died compared with 175 (25%) in the rate-control group (HR 1.06; 95% CI, 0.86 to 1.30; P=0.59) by log rank test. Secondary outcomes, including death from any cause, worsening heart failure, stroke, and composite and death from cardiovascular causes, were also similar in both groups. Patients treated with rhythm control were more likely to be hospitalized than those treated with rate control.9 This trial showed no benefit for use of a routine strategy of rhythm control in patients with AF and systolic heart failure compared with a strategy of rate control.8.1.4.2.4. Recommendation for Combining Anticoagulant With Antiplatelet Therapy (New Section)Multiple studies have demonstrated that oral anticoagulation with warfarin is effective for prevention of thromboembolism in AF patients (Table 3).2,11–16 Aspirin (ASA) offers only modest protection against stroke for AF patients.13,17–23 Adjusted-dose oral anticoagulation is more efficacious than ASA for prevention of stroke in patients with AF.2,24 Recent studies have assessed the thienopyridine antiplatelet agent clopidogrel with ASA for stroke prevention in AF patients.10,25Table 3. Recommendation for Combining Anticoagulant With Antiplatelet Therapy2011 Focused Update RecommendationCommentsClass IIb1. The addition of clopidogrel to aspirin (ASA) to reduce the risk of major vascular events, including stroke, might be considered in patients with AF in whom oral anticoagulation with warfarin is considered unsuitable due to patient preference or the physician's assessment of the patient's ability to safely sustain anticoagulation.10(Level of Evidence: B)New recommendationThe ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) trial25 compared clopidogrel plus ASA with oral anticoagulation therapy with warfarin for prevention of vascular events in AF patients with an average of 2 stroke risk factors. The primary outcome was first occurrence of stroke, noncentral nervous system systemic embolism, myocardial infarction (MI), or vascular death. There were 165 primary events in patients receiving oral anticoagulation therapy (annual risk 3.93%) and 234 in those receiving clopidogrel plus ASA (annual risk 5.60%; RR 1.44; [95% CI, 1.18 to 1.76; P=0.0003; NNT 47]). Although rates of hemorrhage were similar between the 2 groups, significantly greater minor and total bleeds occurred with clopidogrel and ASA than with oral anticoagulation therapy. Major hemorrhages (severe and fatal) occurred in 2.42% of patients treated with clopidogrel plus ASA and in 2.21% of those treated with oral anticoagulation (RR 1.10; 95% CI, 0.83 to 1.45; P=0.53). Total hemorrhagic complications occurred in 15.40% of patients treated with clopidogrel plus ASA and in 13.21% of those treated with oral anticoagulation (RR 1.21; 95% CI, 1.08 to 1.35; P=0.001). The total adverse outcome (primary outcome and major bleeds) was 316 in clopidogrel and ASA and 229 in oral anticoagulation (RR 1.41; 95% CI, 1.19 to 1.67; P<0.001). Oral anticoagulation therapy with warfarin proved superior to clopidogrel plus ASA for prevention of vascular events in AF patients. Treatment with clopidogrel plus ASA was associated with bleeding risk similar to treatment with warfarin.The ACTIVE-A (Effect of Clopidogrel Added to Aspirin in Patients with Atrial Fibrillation) trial assessed whether the addition of clopidogrel to ASA would reduce the risk of vascular events in AF patients who were considered unsuitable for therapy with oral anticoagulation with warfarin10 (Appendix 3). Patients were deemed "unsuitable" for oral anticoagulation due to a specific risk of bleeding (22.9%), patient preference (26%), or physician preference (49.7%). The primary outcome was the composite of stroke, MI, noncentral nervous system systemic embolism, or death from vascular causes. At 3.6 years of follow-up, major vascular events had occurred in 832 patients receiving ASA plus clopidogrel (6.8% per year) and in 924 patients receiving ASA plus placebo (7.6% per year) (RR with clopidogrel 0.89; 95% CI, 0.81 to 0.98; P=0.01). The difference was primarily due to a reduction in the rate of stroke with clopidogrel. Stroke occurred in 296 patients receiving ASA plus clopidogrel (2.4% per year) and in 408 patients receiving placebo (3.3% per year; RR 0.72; 95% CI, 0.62 to 0.83; P<0.001). MI occurred in 90 patients receiving clopidogrel (0.7% per year) and in 115 patients receiving placebo (0.9% per year) (RR 0.78; 95% CI, 0.59 to 1.03; P=0.08). Major bleeding occurred in 251 patients receiving ASA plus clopidogrel (2.0% per year) and in 162 patients receiving ASA plus placebo (1.3% per year; RR 1.57; 95% CI, 1.29 to 1.92; P<0.001). In AF patients for whom oral anticoagulation with warfarin was considered unsuitable, the addition of clopidogrel to ASA reduced the risk of major vascular events, especially stroke, and increased the risk of major hemorrhage.The combined use of dual-antiplatelet therapy with both clopidogrel and ASA plus anticoagulation with warfarin (triple therapy) has been suggested as a strategy for treatment and prevention of complications of 2 or more coexisting conditions such as AF, mechanical valve prosthesis, or the presence of a drug-eluting coronary stent.26 This strategy is associated with an increase in bleeding complications that might range from mild or moderate to severe or life threatening. No prospective randomized trials have been reported addressing this important clinical issue.8.1.4.2.5. Emerging and Investigational Antithrombotic AgentsThe RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial of dabigatran,27 a prodrug that is rapidly converted to an active direct thrombin inhibitor independent of the cytochrome P-450, was reviewed by the 2011 Focused Update Writing Group, but recommendations about its use are not included in this focused update because dabigatran was not approved for clinical use by the FDA at the time of organizational approval.8.1.4.3. Nonpharmacologic Approaches to Prevention of ThromboembolismThe 2011 Focused Update Writing Group considered the Watchman device for atrial appendage closure in its deliberations in anticipation of FDA approval of this device.28 Because the FDA has not approved clinical use of the Watchman device pending the results of additional ongoing trials, the writing group's deliberations and recommendations regarding the Watchman device are not included in the final version of this focused update. A future guideline writing committee will address this and other evolving areas in the management of AF.8.1.8.3. Recommendations for Dronedarone for the Prevention of Recurrent Atrial Fibrillation (New Section)Dronedarone is similar to amiodarone but lacks an iodine moiety. Its multiple electrophysiologic actions include sympatholytic effects as well as inhibition of the L-type calcium current, the inward sodium current, and multiple potassium currents (Table 4).31 Two randomized trials (EURIDIS [European Trial In Atrial Fibrillation or Flutter Patients Receiving Dronedarone for the Maintenance of Sinus Rhythm] and ADONIS [American-Australian-African Trial With Dronedarone in Atrial Fibrillation or Flutter Patients for the Maintenance of Sinus Rhythm]) found that dronedarone prolongs the time to recurrence of AF (Appendix 3).32,33 In patients with persistent AF, DAFNE (Dronedarone Atrial FibrillatioN study after Electrical Cardioversion) showed that administration of dronedarone converted only 5.8% to sinus rhythm (3.1% converted with placebo) and did not improve the acute success of electrical cardioversion.33 Dronedarone slows the ventricular rate in AF by an average of 11 to 13 bpm.33,34 Incidence of spontaneous conversion to sinus rhythm was dose related (ie, 800, 1200, and 1600 mg). The conversion ratio was 5.8% (800 mg), 8.2% (1200 mg), and 14.2% (1600 mg), but the incidence of successful electrical cardioversion was not statistically different between groups (800 mg=77.3%; 1200 mg=87.9%; and 1600 mg=76.6% versus 73.0% in the placebo group).33Table 4. Recommendations for Use of Dronedarone in Atrial Fibrillation2011 Focused Update Recommendati