Atrial fibrillation is one of the most common and complex cardiac arrhythmias. Using currently available evidence, leading medical societies have established recommendations for the optimal management of atrial fibrillation. These guidelines have recently been updated by 4 consensus groups: the European Society of Cardiology, the American College of Chest Physicians, the Canadian Cardiovascular Society, and a task force of 3 societies from the United States: the American College of Cardiology Foundation, the American Heart Association, and the Heart Rhythm Society. The present review focused on the similarities and differences among these recently updated guidelines. Key revisions included updated information on newer treatments for rhythm control, treatment options to reduce atrial fibrillation complications, and updated anticoagulant management for thromboprophylaxis.
An estimated 3 million Americans and 4.5 million Europeans are affected by atrial fibrillation (AF). By 2050, a projected 6 to 16 million Americans will be affected by this arrhythmia, with similar increases expected in Europe. Leading medical societies periodically evaluate medical evidence to provide guidance on the best practices for clinicians. The guidelines for the management of AF have recently been updated by 4 separate consensus groups: the European Society of Cardiology (ESC), the American College of Chest Physicians (ACCP), the Canadian Cardiovascular Society (CCS), and a task force of 3 societies from the United States: the American College of Cardiology Foundation, American Heart Association, and Heart Rhythm Society (ACCF/AHA/HRS). These new guidelines include updated information on newer treatments for rhythm control and treatments to reduce AF complications. Given that much of the morbidity and mortality in AF is due to stroke and thromboembolism, thromboprophylaxis is critical to reduce the embolic risk. Despite these recommendations, many patients with AF do not receive appropriate thromboprophylaxis. This underuse of thromboprophylaxis might be in part because of the dosing complexities of the anticoagulant warfarin. New options for anticoagulation for patients with AF have recently become available and have been described in the new guidelines.
The present review focused on the similarities and differences among this quartet of updated guidelines, highlighting the ACCF/AHA/HRS recommendations and comparing them with the ESC, ACCP, and CCS guidelines.
Methodology Updates
The classification of recommendations and ranking of evidence in the ACCF/AHA/HRS, ESC, ACCP, and CCS guidelines are listed in Tables 1 and 2 . The updated ACCF/AHA/HRS methodology separates class III recommendations into 2 subclasses to delineate whether the recommendation is determined to be of “no benefit” or associated with “harm” to the patient. The CCS also updated its methodology, introducing the Grading of Recommendations Assessment Development and Evaluation system for the classification of recommendations and ranking the evidence level. The ACCP also uses the Grading of Recommendations Assessment Development and Evaluation system, differing only in that the quality of a body of evidence can be high (A), moderate (B), or low (C). For the ninth edition ACCP guidelines (2012), in addition to experts in the field of thrombosis, clinician experts in methodology and the interpretation of evidence were added to the panel and provided the primary leadership responsibilities, allowing a more rigorous application of the ACCP Grading of Recommendations Assessment Development and Evaluation approach than previously.
| ACCF/AHA/HRS | ESC | AACP | CCS |
|---|---|---|---|
| Class I | Class I | Grade 1 (strong) | Strong |
| Conditions for which there is evidence and/or general agreement that a given procedure/therapy is beneficial, useful, and effective | Evidence and/or general agreement that a given treatment or procedure is beneficial, useful, and effective | Benefits clearly outweigh risk and burdens or vice versa | |
| Class II | Class II | Grade 2 (weak) | Conditional (i.e., weak) |
| Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of performing the procedure/therapy | Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure | Benefits closely balanced with risks and burden | |
| Class IIa | Class IIa | ||
| Weight of evidence/opinion is in favor of usefulness/efficacy | Weight of evidence/opinion is in favor of usefulness/efficacy | ||
| Class IIb | Class IIb | ||
| Usefulness/efficacy is less well established by evidence/opinion | Usefulness/efficacy is less well established by evidence/opinion | ||
| Class III | Class III | ||
| Conditions for which there is evidence and/or general agreement that a procedure/therapy is not useful or effective and in some cases could be harmful | Evidence or general agreement that the given treatment or procedure is not useful/effective, and in some cases could be harmful | ||
| COR III—no benefit | |||
| Not useful/effective, no proven benefit | |||
| COR III—harm | |||
| Could be harmful to patient or excess cost without benefit |
| Level of evidence | ACCF/AHA/HRS | ESC | AACP | CCS ∗ |
|---|---|---|---|---|
| A (high) | Data derived from multiple randomized clinical trials or meta-analyses | Data derived from multiple randomized clinical trials or meta-analyses | Consistent evidence from randomized controlled trials without important limitations or exceptionally strong evidence from observational studies | High; future research unlikely to change confidence in estimate of effect (e.g., multiple well-designed, well-conducted clinical trials) |
| B (moderate) | Data derived from a single randomized trial or nonrandomized studies | Data derived from a single randomized clinical trial or large nonrandomized studies | Evidence from randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise) or very strong evidence from observational studies | Moderate; additional research likely to have an important effect on confidence in estimate of effect and might change the estimate (e.g., limited clinical trials, inconsistency of results or study limitations) |
| C (low) | Only consensus opinion of experts, case studies, or standard-of-care | Consensus of opinion of experts and/or small studies, retrospective studies, registries | Evidence for at least 1 critical outcome from observational studies, case series, or randomized controlled trials, with serious flaws or indirect evidence | Low; additional research very likely to have a significant effect on estimate of effect and likely to change estimate (e.g., small number of clinical studies or cohort observations) |
| — | — | — | — | Very low; estimate of effect very uncertain (e.g., case studies, consensus opinion) |
∗ The CCS uses the GRADE system for ranking the level of evidence (high, moderate, low, very low). The CCS also uses other factors in determining the strength of the recommendation: (1) difference between desirable and undesirable effects (the greater the difference between the desirable and undesirable effects, the greater the probability that a strong recommendation is indicated); (2) values and preferences (the greater the variation or uncertainty in values and preferences, the greater the probability that a conditional recommendation is indicated); (3) cost (the greater the cost, the lower the likelihood that a strong recommendation is indicated).
Criteria for Rate Control
The parameters for optimal rate control in patients with AF are controversial and have no standard method of assessment. The new ACCF/AHA/HRS guidelines include a change in the recommended target heart rate—stating that treatment to achieve strict control of the heart rate is not beneficial compared with lenient control. The European and Canadian recommendations have made similar changes, with subtle differences ( Table 3 ).
| New Recommendation | ACCF/AHA/HRS | ESC | ACCP | CCS |
|---|---|---|---|---|
| Heart rate control | Strict rate control (<80 beats/min at rest, <110 beats/min during moderate exercise) not beneficial compared with lenient rate control (<110 beats/min at rest) ∗ (class III—no benefit; level of evidence B) | Initially, lenient rate control, heart rate at rest of <110 beats/min (class IIa; level of evidence B); if symptoms persist or tachycardiomyopathy occurs, use stricter rate control (class IIa; level of evidence B) | NR | Rate control should aim for heart rate at rest of <100 beats/min (strong; high-quality evidence) |
| Combining anticoagulant therapy with antiplatelet therapy | Clopidogrel plus aspirin if OAC is unsuitable (class IIb; level of evidence B); triple therapy generally not recommended | Clopidogrel plus aspirin only if patients refuse OAC and bleeding risk is low (class IIa; level of evidence B); triple therapy: (1) after stenting if thromboembolic risk is moderate to high; (2) in short term after ACS or PCI † (class IIa; level of evidence C) | Triple therapy after stent placement if CHADS 2 ≥2 (grade 2C) | Triple therapy after ACS or PCI if risk of stroke is high (conditional; low-quality evidence) |
| Dronedarone | Is reasonable in patients with paroxysmal AF or after conversion of persistent AF (class IIa; level of evidence B); not for patients with class IV heart failure or patients with recent decompensated heart failure (class III—harm; level of evidence B) | Is reasonable to achieve rate control in patients with recurrent AF (class I; level of evidence A); not for patients with NYHA class III to IV or unstable heart failure (class III; level of evidence B); not for patients in permanent AF (class III) | NR | Can be used along with other agents to optimize rate control (conditional; moderate-quality evidence); not for patients in permanent AF, with a history of heart failure, or LVEF ≤0.40, and not for the sole purpose of rate control (strong; high-quality evidence) |
| Dabigatran | An alternative to warfarin in patients without prosthetic heart valves or hemodynamically significant disease, renal failure, or advanced liver disease (impaired baseline clotting function); 150 mg twice daily in patients with creatinine clearance >30 ml/min; 75 mg twice daily in patients with creatinine clearance 15–30 ml/min (class I; level of evidence B) | Dabigatran, rivaroxaban, ‡ or apixaban ‡ in preference to warfarin (class IIa; level of evidence A) Dabigatran 150 mg twice daily for most patients; 110 mg twice daily for patients ≥80 yrs old, concomitant use of interacting drugs (e.g., verapamil), HAS-BLED score ≥3, or in patients with creatinine clearance 30–49 ml/min (class IIa; level of evidence B) | 150 mg twice daily rather than VKA, except for patients with AF and mitral stenosis, stent, or CHADS 2 ≥1 who experience ACS (grade 2B) | Dabigatran, rivaroxaban, § or apixaban § in preference to warfarin Dabigatran 150 mg twice daily preferable to 110 mg twice daily, except in certain patients ¶ (conditional; high-quality evidence) |
| Catheter-based ablation therapy for maintenance of sinus rhythm | For significantly symptomatic, paroxysmal AF refractory to antiarrhythmic drugs in some patients ‖ (class I; level of evidence A); for symptomatic persistent AF (class IIa; level of evidence A); for symptomatic, paroxysmal AF in patients with significant left atrial dilation or with significant LV dysfunction (class IIb; level of evidence A) | For symptomatic, paroxysmal AF refractory to antiarrhythmic drugs (class I; level of evidence A); first-line treatment of certain patients with AF (class IIa, level of evidence B); antiarrhythmic drugs not a prerequisite in AF patients who remain symptomatic despite rate-control drugs and no significant underlying heart disease (class IIb; level of evidence B); for patients with heart failure and AF refractory to antiarrhythmic drugs (class IIb; level of evidence B) | NR # | For AF refractory to antiarrhythmic drugs in patients in whom rhythm control remains desired (strong; moderate-quality evidence); first-line therapy in highly selected patients with symptomatic, paroxysmal AF (conditional; low-quality evidence) |
∗ In patients with permanent AF with LVEF >0.4 and no or acceptable symptoms related to arrhythmia.
† At 3–6 months after ACS with or without PCI; 4 weeks after elective PCI.
‡ Rivaroxaban was approved for use in Europe in December 2011; the 2012 ECS update has recommended rivaroxaban and included apixaban once approved in Europe (approved in November 2012).
§ Approval for rivaroxaban was obtained in Canada January 2012; the 2012 CCS focused update included rivaroxaban and recommended apixaban once approved by Health Canada (approved in December 2012).
¶ Patients of low body weight, decreased renal function, or at increased risk of major bleeding.
‖ Patients with normal or mildly dilated left atria, normal or mildly reduced LV function, and no severe pulmonary disease.
# The ACCP does not provide specific recommendations for catheter-based ablation in the management of AF.
This change in the recommended target heart rate was largely determined from the results of the Rate Control Efficacy in Permanent Atrial Fibrillation (RACE II) study. The RACE II study found that strict heart rate control in patients with AF was not beneficial compared with lenient control (strict rate control: a heart rate at rest of <80 beats/min and <110 beats/min during moderate exercise; lenient rate control: a heart rate at rest of <110 beats/min). A larger proportion of patients treated with the lenient strategy achieved their target heart rate goal, with lower drug doses and fewer drug combinations, resulting in far fewer outpatient visits to achieve the intended target. In general, lenient rate control is more convenient (requires fewer outpatient visits and examinations) and easier to achieve. Thus, lenient rate control might be a reasonable strategy for patients with permanent AF.
The ACCF/AHA/HRS, ESC, and CCS guidelines have all stated that strict rate control is no longer considered superior to lenient rate control ( Table 3 ). However, the CCS has recommended a heart rate target of <100 beats/min at rest for most patients. This conservative target heart rate might have been in response to the relatively small number of patients in the RACE II trial randomized to the lenient rate control group with a heart rate at rest of >100 to 110 beats/min. Thus, the safety of a heart rate at rest of >100 beats/min might not have been conclusively demonstrated. Additionally, at the end of the first year of the RACE II trial, the difference in the heart rate between the lenient and strict rate-control groups was actually quite small (mean ± SD heart rate at rest of 86 ± 15 and 75 ± 12 beats/min in the lenient and strict rate-control arms, respectively).
The updated ACCP guidelines do not provide criteria for a target heart rate or specific recommendations for rate-control strategies. Previous ACCP guidelines (“Pharmacologic Control of Ventricular Rate,” 2005) provided clinical recommendations for pharmacologic rate control of AF and atrial flutter, but they do not specify a target heart rate.
Criteria for Rate Control
The parameters for optimal rate control in patients with AF are controversial and have no standard method of assessment. The new ACCF/AHA/HRS guidelines include a change in the recommended target heart rate—stating that treatment to achieve strict control of the heart rate is not beneficial compared with lenient control. The European and Canadian recommendations have made similar changes, with subtle differences ( Table 3 ).
| New Recommendation | ACCF/AHA/HRS | ESC | ACCP | CCS |
|---|---|---|---|---|
| Heart rate control | Strict rate control (<80 beats/min at rest, <110 beats/min during moderate exercise) not beneficial compared with lenient rate control (<110 beats/min at rest) ∗ (class III—no benefit; level of evidence B) | Initially, lenient rate control, heart rate at rest of <110 beats/min (class IIa; level of evidence B); if symptoms persist or tachycardiomyopathy occurs, use stricter rate control (class IIa; level of evidence B) | NR | Rate control should aim for heart rate at rest of <100 beats/min (strong; high-quality evidence) |
| Combining anticoagulant therapy with antiplatelet therapy | Clopidogrel plus aspirin if OAC is unsuitable (class IIb; level of evidence B); triple therapy generally not recommended | Clopidogrel plus aspirin only if patients refuse OAC and bleeding risk is low (class IIa; level of evidence B); triple therapy: (1) after stenting if thromboembolic risk is moderate to high; (2) in short term after ACS or PCI † (class IIa; level of evidence C) | Triple therapy after stent placement if CHADS 2 ≥2 (grade 2C) | Triple therapy after ACS or PCI if risk of stroke is high (conditional; low-quality evidence) |
| Dronedarone | Is reasonable in patients with paroxysmal AF or after conversion of persistent AF (class IIa; level of evidence B); not for patients with class IV heart failure or patients with recent decompensated heart failure (class III—harm; level of evidence B) | Is reasonable to achieve rate control in patients with recurrent AF (class I; level of evidence A); not for patients with NYHA class III to IV or unstable heart failure (class III; level of evidence B); not for patients in permanent AF (class III) | NR | Can be used along with other agents to optimize rate control (conditional; moderate-quality evidence); not for patients in permanent AF, with a history of heart failure, or LVEF ≤0.40, and not for the sole purpose of rate control (strong; high-quality evidence) |
| Dabigatran | An alternative to warfarin in patients without prosthetic heart valves or hemodynamically significant disease, renal failure, or advanced liver disease (impaired baseline clotting function); 150 mg twice daily in patients with creatinine clearance >30 ml/min; 75 mg twice daily in patients with creatinine clearance 15–30 ml/min (class I; level of evidence B) | Dabigatran, rivaroxaban, ‡ or apixaban ‡ in preference to warfarin (class IIa; level of evidence A) Dabigatran 150 mg twice daily for most patients; 110 mg twice daily for patients ≥80 yrs old, concomitant use of interacting drugs (e.g., verapamil), HAS-BLED score ≥3, or in patients with creatinine clearance 30–49 ml/min (class IIa; level of evidence B) | 150 mg twice daily rather than VKA, except for patients with AF and mitral stenosis, stent, or CHADS 2 ≥1 who experience ACS (grade 2B) | Dabigatran, rivaroxaban, § or apixaban § in preference to warfarin Dabigatran 150 mg twice daily preferable to 110 mg twice daily, except in certain patients ¶ (conditional; high-quality evidence) |
| Catheter-based ablation therapy for maintenance of sinus rhythm | For significantly symptomatic, paroxysmal AF refractory to antiarrhythmic drugs in some patients ‖ (class I; level of evidence A); for symptomatic persistent AF (class IIa; level of evidence A); for symptomatic, paroxysmal AF in patients with significant left atrial dilation or with significant LV dysfunction (class IIb; level of evidence A) | For symptomatic, paroxysmal AF refractory to antiarrhythmic drugs (class I; level of evidence A); first-line treatment of certain patients with AF (class IIa, level of evidence B); antiarrhythmic drugs not a prerequisite in AF patients who remain symptomatic despite rate-control drugs and no significant underlying heart disease (class IIb; level of evidence B); for patients with heart failure and AF refractory to antiarrhythmic drugs (class IIb; level of evidence B) | NR # | For AF refractory to antiarrhythmic drugs in patients in whom rhythm control remains desired (strong; moderate-quality evidence); first-line therapy in highly selected patients with symptomatic, paroxysmal AF (conditional; low-quality evidence) |
∗ In patients with permanent AF with LVEF >0.4 and no or acceptable symptoms related to arrhythmia.
† At 3–6 months after ACS with or without PCI; 4 weeks after elective PCI.
‡ Rivaroxaban was approved for use in Europe in December 2011; the 2012 ECS update has recommended rivaroxaban and included apixaban once approved in Europe (approved in November 2012).
§ Approval for rivaroxaban was obtained in Canada January 2012; the 2012 CCS focused update included rivaroxaban and recommended apixaban once approved by Health Canada (approved in December 2012).
¶ Patients of low body weight, decreased renal function, or at increased risk of major bleeding.
‖ Patients with normal or mildly dilated left atria, normal or mildly reduced LV function, and no severe pulmonary disease.
# The ACCP does not provide specific recommendations for catheter-based ablation in the management of AF.
This change in the recommended target heart rate was largely determined from the results of the Rate Control Efficacy in Permanent Atrial Fibrillation (RACE II) study. The RACE II study found that strict heart rate control in patients with AF was not beneficial compared with lenient control (strict rate control: a heart rate at rest of <80 beats/min and <110 beats/min during moderate exercise; lenient rate control: a heart rate at rest of <110 beats/min). A larger proportion of patients treated with the lenient strategy achieved their target heart rate goal, with lower drug doses and fewer drug combinations, resulting in far fewer outpatient visits to achieve the intended target. In general, lenient rate control is more convenient (requires fewer outpatient visits and examinations) and easier to achieve. Thus, lenient rate control might be a reasonable strategy for patients with permanent AF.
The ACCF/AHA/HRS, ESC, and CCS guidelines have all stated that strict rate control is no longer considered superior to lenient rate control ( Table 3 ). However, the CCS has recommended a heart rate target of <100 beats/min at rest for most patients. This conservative target heart rate might have been in response to the relatively small number of patients in the RACE II trial randomized to the lenient rate control group with a heart rate at rest of >100 to 110 beats/min. Thus, the safety of a heart rate at rest of >100 beats/min might not have been conclusively demonstrated. Additionally, at the end of the first year of the RACE II trial, the difference in the heart rate between the lenient and strict rate-control groups was actually quite small (mean ± SD heart rate at rest of 86 ± 15 and 75 ± 12 beats/min in the lenient and strict rate-control arms, respectively).
The updated ACCP guidelines do not provide criteria for a target heart rate or specific recommendations for rate-control strategies. Previous ACCP guidelines (“Pharmacologic Control of Ventricular Rate,” 2005) provided clinical recommendations for pharmacologic rate control of AF and atrial flutter, but they do not specify a target heart rate.
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