2011 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
- AHA Scientific Statements
- atrial fibrillation
- rate control
- rhythm control
- anticoagulant therapy
- antiplatelet therapy
- antithrombotic agents
- catheter ablation
A 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; and
need 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.
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 Guidelines
1.1. Methodology and Evidence Review
Late-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.2
To 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 Committee
For 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 Approval
This 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.
This 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 Fibrillation
CRITERIA 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.8
The 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.
126.96.36.199.4. 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.10,25
The 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.
188.8.131.52.5. Emerging and Investigational Antithrombotic Agents
The 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.
184.108.40.206. Nonpharmacologic Approaches to Prevention of Thromboembolism
The 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.
220.127.116.11. 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).33
Dronedarone is generally less efficacious than amiodarone.35 The DIONYSOS (Efficacy & Safety of Dronedarone Versus Amiodarone for the Maintenance of Sinus Rhythm in Patients With Persistent Atrial Fibrillation) study was a short-term, randomized, double-blind, parallel-group study that evaluated the efficacy and safety of dronedarone versus amiodarone.36 In patients with persistent AF, dronedarone was less effective than amiodarone in decreasing AF recurrence in 504 patients with persistent AF randomized to treatment with either dronedarone or amiodarone, but it was better tolerated (Appendix 3). The primary composite endpoint was recurrence of AF (including unsuccessful electrical cardioversion, no spontaneous conversion, and no electrical cardioversion) or premature study discontinuation was achieved in 75.1% of patients taking dronedarone and 58.8% taking amiodarone at 12 months (HR 1.59; 95% CI, 1.28 to 1.98; P<0.0001). Premature discontinuation of study drug occurred in 10.4% of the dronedarone group and 13.3% of the amiodarone group. Main safety endpoints were observed in 39.3% of dronedarone patients versus 44.5% of amiodarone patients (HR 0.80; 95% CI, 0.60 to 1.07; P=0.129). Fewer thyroid, neurologic, dermatologic, and ocular events occurred in the dronedarone group.
The ATHENA (A placebo-controlled, double-blind, parallel arm Trial to assess the efficacy of dronedarone 400 mg bid for the prevention of cardiovascular Hospitalization or death from any cause in patiENts with Atrial fibrillation/atrial flutter) trial included patients with paroxysmal or persistent AF or atrial flutter and risk factors for thromboembolism29 (Appendix 3). Dronedarone reduced the combined endpoint of death and cardiovascular hospitalizations, largely by reducing hospitalizations related to AF (and cardiovascular death); death from any cause was not reduced.29 Maintenance of sinus rhythm was not a discrete endpoint in this trial. Fewer strokes occurred in the dronedarone group, although this effect was not prespecified and requires confirmation by other trials.37 The ATHENA trial excluded patients with decompensated heart failure within the previous 4 weeks, or with NYHA class IV heart failure. There was no evidence of an adverse effect of dronedarone in patient subgroups with a history of congestive heart failure or LV ejection fraction <35%.29 Note that evidence of efficacy is based on reduced hospitalization for AF, acute coronary syndrome and all cause mortality, not maintenance of sinus rhythm.
In a trial of patients with recently decompensated heart failure and depressed LV function, ANDROMEDA (Antiarrhythmic Trial with Dronedarone in Moderate to Severe CHF Evaluating Morbidity Decrease), dronedarone increased mortality after a median follow-up of only 2 months; 8.1% in the dronedarone group died and 3.8% in the placebo group died (HR 2.13; 95% CI, 1.07 to 4.25; P=0.03) (Appendix 3).30 The higher mortality was associated with more progression of heart failure. Therefore, dronedarone should not be administered to patients with depressed ventricular function and recent heart failure decompensation or NYHA class IV heart failure.
The major adverse cardiac effects of dronedarone are bradycardia and QT prolongation. Torsades de pointes has been reported.29 Like amiodarone, dronedarone inhibits renal tubular secretion of creatinine, which can increase plasma creatinine levels. However, there is no reduction in glomerular filtration rate. Dronedarone increases digoxin levels 1.7- to 2.5-fold.31 Dronedarone is predominantly metabolized by the liver (CYP3A4) with a half-life of approximately 19 hours. It should not be administered with strong inhibitors of CYP3A4 (eg, ketoconazole and macrolide antibiotics) because these may potentiate the effects of dronedarone. It can be administered with verapamil or diltiazem, which are moderate CYP3A4 inhibitors, but low doses of these agents should be used initially and titrated according to response and tolerance.31 Dronedarone does not alter the international normalization ratio when used with warfarin. The recommended oral dose of dronedarone is 400 mg twice a day with meals. An intravenous form is not available.
8.3. Maintenance of Sinus Rhythm
8.3.1. Recommendations for Therapy
18.104.22.168. Future Directions in Catheter-Based Ablation Therapy for Atrial Fibrillation (New Section)
Catheter ablation to maintain sinus rhythm has been reported in trials and meta-analyses including data from more than 6900 patients.38–51 Patients undergoing ablation are a selected population characterized by a predominance of those with symptomatic paroxysmal AF that has failed treatment with one or more antiarrhythmic drugs, with normal size or mildly dilated atria, normal or mildly reduced ventricular function, and absence of severe pulmonary disease. Following ablation, most patients are free of recurrent, paroxysmal AF for 1 year or more.
In the ThermoCool trial, a randomized multicenter study of 167 symptomatic patients with paroxysmal AF who had not shown improvement with at least 1 antiarrhythmic drug, radiofrequency catheter ablation with pulmonary vein isolation resulted in significantly fewer episodes of recurrent AF than did treatment with additional antiarrhythmic drugs51 (Appendix 3). Quality-of-life and symptom severity scores were significantly better after 3 months in the group treated with catheter ablation. Major treatment-related adverse events were similar between catheter-treated and drug-treated groups at 30 days. More than 5000 patients were screened to recruit these 167 study subjects. Important exclusions included patients with AF >30 days' duration, ejection fraction <40%, left atrial diameter >5 cm, severe pulmonary disease, recent MI, coronary artery bypass graft surgery, thromboemboli, treatment with amiodarone, or previous catheter ablations for AF.51 The average age of patients undergoing catheter ablation was relatively young at 55.7 years (95% CI, 54.1 to 57.4), and they had paroxysmal, symptomatic AF for a relatively long time: 5.7 years (95% CI, 4.8 to 6.6). All ablation procedures were performed by highly experienced operators in high-volume centers. Although the primary endpoint in all centers was electrical isolation of all pulmonary veins in each patient who underwent AF ablation, other aspects of the ablation procedures were not standardized, including the use of linear lesions. Repeat catheter ablation procedures were performed in 12.6% of the ablation group. Ultimately, 34% of ablation patients had recurrence of symptomatic AF during the 9-month follow-up period, compared with 84% of the drug-treated group.51 In this highly selected patient population, in patients for whom 1 antiarrhythmic drug has failed, subsequent antiarrhythmic drug treatment is likely to fail; such patients may benefit from catheter ablation.
Despite these advances, the long-term efficacy of catheter ablation to prevent recurrent AF requires further study. Available data demonstrate 1 year or more of freedom from recurrent AF in most (albeit carefully selected) patients.69–71 However, AF can recur without symptoms and be unrecognized by the patient or physician. There is uncertainty as to what the risk of recurrence of AF is over the long term, because AF may recur with minimal symptoms. This distinction has important implications for the duration of anticoagulation therapy in patients with risk factors for stroke associated with AF. In addition, little information is yet available about the late success of ablation in patients with heart failure and other advanced structural heart disease, who may be less likely to enjoy freedom from recurrence of AF.72
American College of Cardiology Foundation
John C. Lewin, MD, Chief Executive Officer
Charlene May, Senior Director, Science and Clinical Policy
Lisa Bradfield, CAE, Director, Science and Clinical Policy
Sue Keller, BSN, MPH, Senior Specialist, Evidence-Based Medicine
Erin A. Barrett, MPS, Senior Specialist, Science and Clinical Policy
Beth Denton, Specialist, Science and Clinical Policy
American Heart Association
Nancy Brown, Chief Executive Officer
Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice President, Office of Science Operations
2006 Writing Committee Members
Valentin Fuster, MD, PhD, FACC, FAHA, FESC, Co-Chair; Lars E. Rydén, MD, PhD, FACC, FESC, FAHA, Co-Chair; David S. Cannom, MD, FACC*; Jean-Yves Le Heuzey, MD, FESC*; Harry J. Crijns, MD, FACC, FESC¶; James E. Lowe, MD, FACC*; Anne B. Curtis, MD, FACC, FAHA*; S. Bertil Olsson, MD, PhD, FESC*; Kenneth A. Ellenbogen, MD, FACC, FHRS; Eric N. Prystowsky, MD, FACC*; Jonathan L. Halperin, MD, FACC, FAHA*; Juan Luis Tamargo, MD, FESC*; G. Neal Kay, MD, FACC*; 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; Judith S. Hochman, MD, FACC, FAHA; Christopher E. Buller, MD, FACC#; Frederick G. Kushner, MD, FACC, FAHA; Mark A. Creager, MD, FACC, FAHA; Erik Magnus Ohman, MD, FACC; Steven M. Ettinger, MD, FACC; William G. Stevenson, MD, FACC, FAHA; Robert A. Guyton, MD, FACC; Lynn G. Tarkington, RN#; Jonathan L. Halperin, MD, FACC, FAHA; Clyde W. Yancy, MD, FACC, FAHA
¶European Society of Cardiology Representative.
#Former Task Force member during this writing effort.
This document was approved by the American College of Cardiology Foundation Board of Trustees in July 2010, by the American Heart Association Science Advisory and Coordinating Committee in August 2010, and by the Heart Rhythm Society in August 2010.
The American Heart Association requests that this document be cited as follows: Wann LS, Curtis AB, January CT, Ellenbogen KA, Lowe JE, Estes NAM 3rd, Page RL, Ezekowitz MD, Slotwiner DJ, Jackman WM, 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 (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 2011;123:104–123.
This article has been copublished in the Journal of the American College of Cardiology and HeartRhythm.
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- © 2011 by the American College of Cardiology Foundation, the American Heart Association, Inc., and the Heart Rhythm Society.
ACCF/AHA Task Force on Practice Guidelines. Methodologies and policies from the ACCF/AHA Task Force on Practice Guidelines. Available at: http://assets.cardiosource.com/Methodology_Manual_for_ACC_AHA_Writing_Committees.pdf and http://circ.ahajournals.org/manual/. Accessed July 2, 2010.
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