INTRODUCTION — Atrial fibrillation (AF) is the most common sustained arrhythmia. It may cause significant symptoms and impair both functional status and quality of life. Without therapeutic intervention, affected patients are at increased risk for mortality (1.5- to 1.9-fold in the Framingham Heart Study) and morbidity (thromboembolic events and limiting symptoms).
In AF, the loss of the regular and organized left atrial contraction, as well as the subsequent increase in ventricular rate, lead to both immediate and long-term adverse consequences: deterioration in hemodynamics secondary to increased heart rate and loss of atrioventricular (AV) synchrony, an increased risk for stroke and other embolic events from left atrial thrombi, and progressive dysfunction of the left atrium and left ventricle [1,2]. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm" and "Arrhythmia-induced cardiomyopathy".)
For each patient with AF, the two principal goals of therapy are symptom control and the prevention of thromboembolism. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Adverse hemodynamics in AF'.)
Rate- and rhythm-control strategies improve symptoms, but neither has been conclusively shown to improve survival compared with the other, perhaps with the exception of high-cardiovascular-risk patients who are treated early in the course of their disease. (See 'Definitions' below and 'EAST-AFNET 4' below.)
A decision should be made as to which approach will be used for long-term management. The following points should be kept in mind irrespective of strategy:
●Both strategies can fail both in the short and in the long terms. Consequently, many patients need to be reconsidered for the alternate strategy as the natural history of their disease progresses.
●All patients with AF, irrespective of strategy chosen/rhythm, should have their thromboembolic risk assessed and be managed accordingly. (See 'Thromboembolic risk' below.)
●For patients who are managed with a rhythm-control strategy, rate control is necessary due to the possibility of the recurrence of AF.
The advantages and disadvantages of rhythm and rate control, as well as whether there are subgroups of patients for whom one or the other should be preferred, will be discussed here. The methods to achieve rhythm or rate control are discussed separately. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations" and "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy" and "Atrial fibrillation: Atrioventricular node ablation".)
NEW ATRIAL FIBRILLATION — For patients who present with new AF, relatively rapid decisions, including the choice between rhythm and rate control, often need to be made. This issue is discussed in detail separately. (See "New onset atrial fibrillation".)
DEFINITIONS — A rhythm-control strategy uses antiarrhythmic drug therapy, radiofrequency catheter ablation of the left atrium in the electrophysiology laboratory, and/or an ablation procedure performed at the time of open heart surgery to maintain sinus rhythm (SR). Many patients who remain in SR require long-term rate-slowing drugs (in the event of return to atrial fibrillation), as well as chronic antithrombotic therapy. (See 'Thromboembolic risk' below.)
A rate-control strategy uses drugs that block (slow conduction through) the atrioventricular (AV) node such as beta blockers, rate-slowing calcium channel blockers, or digoxin. AV nodal ablation plus ventricular pacing to control symptoms is also considered when pharmacologic therapy is ineffective. Rate control goals are discussed elsewhere. (See "Control of ventricular rate in atrial fibrillation: Pharmacologic therapy", section on 'Long-term rate control goals'.)
THROMBOEMBOLIC RISK — Thromboembolism is the most important adverse outcome of atrial fibrillation (AF). Unfortunately, clinical maintenance of sinus rhythm (SR) does not reduce the frequency of clinical thromboembolization. The AFFIRM and RACE trials demonstrated that embolic events occurred with equal frequency regardless of whether a rate control or rhythm-control strategy was pursued; furthermore, most embolic events (113 of 157 ischemic strokes in AFFIRM and 29 of 35 embolic events in RACE) occurred after warfarin had been stopped or when the International Normalized Ratio (INR) was subtherapeutic (less than 2.0) [3,4]. These findings indicate that at-risk patients in whom a rhythm-control strategy is pursued still require chronic anticoagulation, even if it seems that SR is maintained. (See "Atrial fibrillation in adults: Use of oral anticoagulants".)
There are at least three explanations for the failure of rhythm control to reduce embolic risk:
●Despite successful cardioversion and antiarrhythmic drug therapy, the recurrence rate of either intermittent (paroxysmal) or persistent AF is 35 to 60 percent at one year with intermittent monitoring (figure 1) [5,6] and up to 88 percent with continuous monitoring (permanent pacemaker with AF detection function and electrogram storage) for more than 18 months [7]. In the AFFIRM trial described below, there was a high crossover rate from rhythm to rate control (17 and 38 percent of patients at one and five years), due primarily to inability to maintain SR and drug intolerance [3].
Up to 90 percent of AF recurrences are asymptomatic [8] (likely because of the use of ventricular rate controlling medications) and asymptomatic episodes lasting more than 48 hours are not uncommon, occurring in 17 percent of patients in a report using continuous monitoring [7]. During these prolonged episodes of AF, left atrial appendage thrombi can form that may cause clinical thromboembolism. The continuous monitoring study also showed that 40 percent of patients had episodes of AF-like symptoms in the absence of AF [7]. Even very brief episodes of AF can increase stroke risk. In a study using pacemakers for arrhythmia detection in patients without a history of AF, AF duration for greater than five minutes increased the risk of thromboembolic events sixfold compared with patients with similar or greater CHADS2 score and no detected AF [9].
●Patients with nonvalvular AF that is not due to a reversible disease (eg, hyperthyroidism, cardiac surgery) often have other predisposing factors for thromboembolism even when they are in SR. These include complex aortic plaque and left ventricular systolic dysfunction. (See "Antithrombotic therapy in patients with heart failure" and "Thromboembolism from aortic plaque".)
●There may be discordance between the body of the left atrium, demonstrating sinus mechanism, while the atrial appendage displays an AF contraction pattern [10].
●Thus, the implementation of either strategy requires the assessment of the need for antithrombotic therapy. Issues related to risk stratification and the approach to antithrombotic therapy in patients with AF are discussed in detail separately. (See "Atrial fibrillation in adults: Use of oral anticoagulants".)
A separate issue from chronic antithrombotic therapy is anticoagulation related to cardioversion. The recommended approach to such patients is presented separately. (See "Prevention of embolization prior to and after restoration of sinus rhythm in atrial fibrillation".)
COMPARATIVE STUDIES — At least seven randomized trials have compared rate and rhythm control using antiarrhythmic drug therapy in a broad population of patients with AF [3,4,11-13]. In the aggregate, these studies demonstrated equivalent outcomes, such as the rates of death or embolism, in both arms. One trial demonstrated improved quality-of-life scores with rhythm control [14]. However, a 2020 study of early AF patients (first diagnosed within a year of enrollment) with baseline cardiovascular disease found a lower risk of cardiovascular outcomes, including death, compared with usual care when catheter ablation was allowed in the rhythm control arm [15].
AFFIRM and RACE — Unlike the EAST-AFNET 4 trial discussed below, the older AFFIRM and RACE randomized trials did not include catheter ablation in the rhythm control arm and included patients with AF of much longer duration from first presentation (median nearly a year for RACE compared with 36 days for EAST-AFNET).
●AFFIRM: AFFIRM randomly assigned 4060 patients with recurrent AF to rate control (using digoxin, beta blocker, and/or calcium channel blocker) and anticoagulation with warfarin or to rhythm control with the most effective antiarrhythmic drug, with the use of warfarin left up to the discretion of the investigator [3]. Patients had to be at least 65 years of age (mean age 70) or have other risk factors for stroke or death and there could be no contraindications to antiarrhythmic or anticoagulation therapy. All patients were initially anticoagulated, but those in the rhythm control arm who maintained sinus rhythm (SR) could be withdrawn from warfarin.
In the rate control arm of the study, the goals were a ventricular rate of 80 beats per min at rest and 110 beats per minute during a six-minute walk test. At five years, 35 percent of patients were in SR (compared to 63 percent with rhythm control), while over 80 percent of those still in AF had "adequate heart rate control." Over 85 percent of patients in the rate control arm were treated with warfarin. Radiofrequency ablation of the atrioventricular node (AV) was required in 105 patients (5 percent) (see "Atrial fibrillation: Atrioventricular node ablation").
In the rhythm control arm of the study, SR was maintained in 82 and 63 percent of patients at one and five years; only 1 percent underwent nonpharmacologic therapy to maintain rhythm control. The most frequently used initial antiarrhythmic drugs were amiodarone (38 percent) and sotalol (31 percent). By the end of 3.5 years of follow-up, 63 percent of patients had had at least one trial of amiodarone.
Among patients initially assigned to rhythm control, crossover to rate control occurred in 17 and 38 percent of patients at one and five years, primarily due to inability to maintain SR and drug intolerance. In those originally assigned to rate control, the crossover rate to rhythm control was lower at 8 and 15 percent, primarily due to failure to control symptoms due to AF and heart failure.
After a mean follow-up of 3.5 years, the following findings were observed:
•There was a trend toward a decrease in the rate of occurrence of the primary end point (all-cause mortality) with rate control (21.3 versus 23.8 percent, hazard ratio [HR] 0.87, 95% CI 0.75-1.01) (figure 2). There was no difference between the two groups in the incidence of cardiac death, arrhythmic death, or deaths due to ischemic or hemorrhagic stroke [16]. Two prespecified subgroups had a significant reduction in mortality with rate control: those without a history of heart failure (adjusted HR 0.69) and those aged 65 years or older (HR 0.76) [17].
•There was no significant difference in the composite secondary end point of death, ischemic stroke, anoxic encephalopathy, major bleeding, or cardiac arrest.
•There was no significant difference in global functional status or quality of life in the initial report.
•The number of patients requiring hospitalization during follow-up was significantly lower in the rate control group than in the rhythm control group (73 versus 80 percent).
A subsequent report provided evidence that the trend toward increased mortality with rhythm control was due to the deleterious effects of antiarrhythmic drugs [18]. In this analysis, the use of antiarrhythmic drugs was associated with a significant increase in mortality (HR 1.49), while the presence of SR was associated with a significant reduction in mortality (hazard ratio 0.53). It could not be determined if the latter effect was due to SR itself or to AF being a marker for a confounding factor or factors that affect survival, such as heart failure [19].
●RACE: The RACE trial enrolled 522 patients (mean age 68) with recurrent persistent AF or atrial flutter of less than one year in duration (median 33 days for the index episode but median of <300 days history of AF) who had required one to two cardioversions within the prior two years [4]. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Classification and terminology'.)
Patients were randomly assigned to rate control using the same AV nodal blocking drugs as used in AFFIRM or to rhythm control. Successful rate control was defined as a ventricular rate below 100 beats/min and no symptoms. Initial therapy for rhythm control was sotalol. If AF recurred within six months, antiarrhythmic drug therapy was changed; if AF again recurred within six months, amiodarone was substituted. A late recurrence, after more than six months of therapy, was treated with repeat cardioversion and continuation of the same antiarrhythmic agent.
The primary end point was a composite of cardiovascular death, admission for heart failure, thromboembolic event, severe bleeding, pacemaker implantation, or severe side effects from antiarrhythmic drugs. After a mean 2.3-year follow-up, the following findings were observed:
•Significantly fewer patients were in SR in the rate control group (10 versus 39 percent).
•There was an almost significant trend toward a lower incidence of the primary end point with rate control (17.2 versus 22.6 percent with rhythm control, HR 0.73, 90% CI 0.53-1.01) (figure 3). There was no difference in cardiovascular mortality (6.8 versus 7 percent). However, there was a trend toward a higher incidence of nonfatal end points among patients assigned to rhythm control, including heart failure, thromboembolism, pacemaker insertion, and adverse drug reactions.
•There were no significant differences in quality of life between the rate and rhythm control groups, a finding similar to that in AFFIRM [20]. Improvement in quality of life was associated with symptomatic AF at baseline, a short duration of AF, and the presence of SR at the end of follow-up, rather than the assigned strategy.
Limitations of these trials — Limitations of the RACE and AFFIRM trials include:
●The mean ages in AFFIRM and RACE were 70 and 68 years, respectively [3,4]. It is therefore uncertain if younger healthy patients might benefit from more aggressive rhythm control [21,22].
●Approximately one-half of patients in AFFIRM who had a detailed history had symptomatic episodes of AF that occurred less often than once per month [23]. Such patients would be expected to derive little symptomatic benefit from rhythm control, and the results may not directly apply to patients with frequent episodes of symptomatic AF [19].
●The use of antiarrhythmic drugs in AFFIRM was associated with a significant increase in mortality (HR 1.49), which was due to non-cardiovascular causes, while the presence of SR was associated with a significant reduction in mortality (HR 0.53) [16,18]. A similar benefit from being in sinus rhythm (relative risk 0.44) was noted in the DIAMOND trial that compared dofetilide to placebo in patients with reduced left ventricular systolic function [24]. (See "The management of atrial fibrillation in patients with heart failure".)
One interpretation of these data is that maintenance of SR might be beneficial if there were a safer and more effective approach than current antiarrhythmic drugs [19,25]. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Sequelae'.)
●The AFFIRM and RACE data were largely gathered before catheter ablation. The potential impact of this procedure (versus chronic antiarrhythmic therapy) remains incompletely explored (see "Atrial fibrillation: Catheter ablation"). Catheter ablation and antiarrhythmic drug therapy were used in the rhythm control arm of the EAST-AFNET 4 trial. (See 'EAST-AFNET 4' below.)
●Both trials allowed for cessation of anticoagulant therapy four weeks after documentation of SR, leading to a higher rate of stroke. It has been postulated that continued anticoagulation might have led to a lower mortality in the rhythm control group [26].
EAST-AFNET 4 — In addition to thromboembolic complications, AF patients are at increased risk for adverse cardiovascular events, including cardiovascular death (see "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Mortality'). The EAST-AFNET 4 trial randomly assigned 2789 patients with early AF (defined as AF diagnosed ≤12 months before enrollment; median time since diagnosis, 36 days) and at high risk for cardiovascular complications to either early rhythm control with antiarrhythmic drugs or ablation or to usual care, which limited rhythm control to patients with unacceptable symptoms after rate control [15]. High risk was defined as >75 years of age, prior transient ischemic attack or stroke, or two of the following criteria: age >65 years, female sex, heart failure, hypertension, diabetes, severe coronary artery disease, chronic kidney disease, and left ventricular hypertrophy (diastolic septal wall width >15 mm).
The trial was stopped early for efficacy after a median of 5.1 years of follow-up. The following findings were reported:
●The primary composite outcome (eg, cardiovascular death, stroke, or serious adverse events related to rhythm-control therapy) occurred less often with rhythm control (249 versus 316 events, respectively; 3.9 versus 5.0 events per 100 person-years; hazard ratio [HR] 0.79, 95% CI 0.66-0.94).
●Death from cardiovascular causes occurred less often in the rhythm-control group (67 versus 94 events, respectively; 1.0 versus 1.3 percent, HR 0.72, 95% CI 0.52-0.98).
●Stroke occurred less often in the rhythm-control group (40 versus 62 events, respectively; 0.6 versus 0.9 percent, HR 0.65, 95% CI 0.44-0.97).
●More than 70 percent of patients were asymptomatic in both treatment groups at one and two years.
●There was no significant difference between the two groups in the rate of the primary safety outcome (eg, death, stroke, and serious adverse event related to the rhythm-control strategy).
●Serious adverse events related to rhythm-control therapy were uncommon but were more frequent in the rhythm-control group (4.9 versus 1.4 percent).
In a post-hoc analysis of EAST-AFNET4, rates of the primary composite outcome did not differ among symptomatic and asymptomatic patients [27]. The primary outcome occurred in 79 of 395 asymptomatic patients randomized to early rhythm control and in 97 of 406 patients randomized to usual care (HR 0.76, 95% CI 0.6-1.03). This benefit from early rhythm control was similar to that seen in symptomatic patients (HR 0.79; 95% CI 0.6-0.98). The study was not powered to detect a difference between patients with and without symptoms.
CHOICE OF THERAPY — In the broad population of patients with AF, the decision regarding the choice between rhythm or rate control should be made after a detailed discussion with the patient of the benefits and risks of each approach. While it seems intuitive that an individual patient would feel better in SR than in AF (even with rate control), not all such patients feel better. In many cases, the benefits and risks will be closely balanced and either strategy will be a reasonable choice.
●For many asymptomatic patients, we prefer rate control as the initial approach, particularly if the AF is longstanding.
●For many symptomatic patients, particularly those at high risk for a cardiovascular event and AF diagnosed within one year, we prefer rhythm control as the initial approach.
Preference for rate control — In many asymptomatic patients with atrial fibrillation (AF), particularly long-standing, recurrent AF, we prefer rate control as the initial approach [19,21,22,28]. This is based upon the following factors:
●The results from AFFIRM and RACE show equivalent and perhaps better outcomes with rate control (figure 2 and figure 3) among patients with longstanding atrial fibrillation [3,4]. A meta-analysis of five trials, in which AFFIRM accounted for 77 percent of the patients, found a strong trend toward a reduction in all-cause mortality with rate control (13.0 versus 14.6 percent with rhythm control, odds ratio 0.87, 95% CI 0.74-1.02) [29]. The proportion of patients who had an ischemic stroke was similar with the two approaches (3.5 versus 3.9 percent).
●Important side effects, especially proarrhythmia, are associated with antiarrhythmic drugs [18,30-32]. In addition, catheter ablation is associated with important complications. (See "Atrial fibrillation: Catheter ablation", section on 'Complications'.)
●There is an appreciable rate of recurrent AF and frequent crossover to a rate-control strategy when antiarrhythmic drugs are used for maintenance therapy after conversion to sinus rhythm (SR). Recurrence is detected clinically in 20 to 60 percent at one year (figure 1) [33]. Furthermore, a continuous monitoring study found that recurrent episodes occurred in approximately 90 percent of patients; many of these episodes were asymptomatic, including some lasting more than 48 hours [7]. The risk of recurrent AF is highest in patients who have hypertension, an enlarged left atrium, AF for more than one year, or heart failure [34].
Very elderly — Patients over age 80 account for approximately 35 percent of patients with AF and the prevalence of AF is about 10 percent (figure 4) [35]. Historically, rate control has often been preferred in such patients for the following reasons:
●They are more sensitive to the proarrhythmic effects of drugs
●AF is often permanent
●AF is often asymptomatic
However, the EAST-AFNET 4 trial of patients with first-onset AF within one year expands the evidence base with which recommendations can be made for the very elderly, as over 25 percent of patients were older than 75 years. (See 'EAST-AFNET 4' above.)
Preference for rhythm control — There are several situations in which rhythm control is preferable [21].
High-cardiovascular-risk patients — The EAST-AFNET 4 trial demonstrated a slightly improved survival with rhythm control in high-cardiovascular-risk patients if this strategy is employed within 12 months of the initial diagnosis. High risk includes >75 years of age, prior transient ischemic attack or stroke, or two of the following criteria: age >65 years, female sex, heart failure, hypertension, diabetes, severe coronary artery disease, chronic kidney disease, and left ventricular hypertrophy (diastolic septal wall width >15 mm). (See 'EAST-AFNET 4' above.)
Failure of rate control — There are two manifestations of failure of rate control:
●Persistent symptoms (palpitations, dyspnea, lightheadedness, angina, and near syncope) despite adequate rate control. (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm".)
●An inability to attain adequate rate control as defined above. In these patients, alternatives to rhythm control with antiarrhythmic drug therapy include radiofrequency catheter ablation of the AV node with pacemaker insertion or radiofrequency catheter ablation. (See "Atrial fibrillation: Atrioventricular node ablation" and "Atrial fibrillation: Catheter ablation".)
Heart failure — Rhythm control is generally preferred in symptomatic patients, especially those with heart failure. This issue is discussed in detail separately. (See "The management of atrial fibrillation in patients with heart failure", section on 'Preference for rhythm over rate control'.)
Younger patients — Younger individuals (less than 65 years), or those who need to carry out activities requiring optimal cardiac performance, generally do not tolerate AF. When antiarrhythmic drugs are used in this setting, patients should be well informed of the benefits and risks of this therapy.
RECOMMENDATIONS OF OTHERS — Recommendations regarding the choice between rate and rhythm control are available from the American Heart Association/American College of Cardiology (2014, 2019) and the European Society of Cardiology (2016) [36-39].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Atrial fibrillation" and "Society guideline links: Arrhythmias in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: Atrial fibrillation (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●For each patient with atrial fibrillation (AF), the two principal goals of therapy are symptom control and the prevention of thromboembolism. (See "Atrial fibrillation in adults: Use of oral anticoagulants" and "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Adverse hemodynamics in AF'.)
●In patients not at high cardiovascular risk, rhythm- and rate-control strategies are associated with similar rates of mortality and serious morbidity, such as embolic risk. (See 'Thromboembolic risk' above.)
Assessments of quality of life have not shown significant differences between the two in most studies. (See 'Definitions' above.)
●When deciding between rhythm and rate control, the patient's symptom status, duration of AF, and cardiovascular risk, among other factors, should be considered. Our approach to choosing between a rhythm- and a rate-control strategy in patients with AF is as follows:
•For patients with newly diagnosed AF who are at high risk for cardiovascular complications and especially if the patient is symptomatic, we suggest a rhythm-control rather than a rate-control strategy, provided it can be initiated within 12 months of onset (Grade 2C). High risk is defined as >75 years of age, prior transient ischemic attack or stroke, or two of the following criteria: age >65 years, female sex, heart failure, hypertension, diabetes, severe coronary artery disease, chronic kidney disease, and left ventricular hypertrophy (diastolic septal wall width >15 mm). (See 'EAST-AFNET 4' above.)
•For all other patients, after considering duration of AF, cardiovascular risk, and symptom status, either a rate- or a rhythm-control strategy is reasonable.
Patients for whom a rhythm-control strategy may be reasonable include those who continue with clinically significant symptoms on a rate-control strategy, patients with a history of heart failure, or younger patients. (See 'Preference for rhythm control' above.)
Patients for whom a rate-control strategy may be reasonable include those who are asymptomatic or those concerned about the potential side effects of antiarrhythmic drug therapy or potential complications of catheter ablation. Simplification of the medical regimen and lower cost are additional reasons. (See 'Preference for rate control' above.)
