Version May 2024
INTRODUCTION — For patients with atrial fibrillation (AF), the two principal goals of long-term therapy are to improve quality of life (eg, symptom control) and to prevent associated morbidity and mortality (principally the prevention of thromboembolism). (See "Hemodynamic consequences of atrial fibrillation and cardioversion to sinus rhythm", section on 'Adverse hemodynamics in AF' and "Atrial fibrillation in adults: Use of oral anticoagulants".)
In asymptomatic patients with AF, there may be no need to pursue aggressive measures to maintain sinus rhythm, particularly in older individuals with longstanding persistent AF and without associated left ventricular dysfunction. For those patients who might feel better in sinus rhythm, rhythm-control strategies improve symptoms greater than rate control, but neither has been conclusively shown to improve survival compared with the other. The factors determining the choice between these two strategies are discussed elsewhere. (See "Management of atrial fibrillation: Rhythm control versus rate control".)
For those patients in whom a rhythm control strategy is chosen, catheter ablation or antiarrhythmic drugs are the two principle therapeutic options. (See "Atrial fibrillation: Catheter ablation" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations".)
This topic will compare the efficacy and safety of these two options for rhythm control and provide recommendations for choosing one or the other.
CLASSIFICATION — The following terms are used in the classification of patients with atrial fibrillation (AF). In the studies discussed in this topic, some, but not all, of these groups have been included (see "Atrial fibrillation: Overview and management of new-onset atrial fibrillation", section on 'Classification and terminology'):
●Paroxysmal (ie, self-terminating or intermittent) AF – Paroxysmal AF is defined as recurrent AF (≥2 episodes) that terminates spontaneously in seven days or less, usually less than 24 hours. (See "Paroxysmal atrial fibrillation".)
●Persistent AF – Persistent AF is defined as AF that fails to self-terminate within seven days. Episodes often require pharmacologic or electrical cardioversion to restore sinus rhythm. While a patient who has had persistent AF can have later episodes of paroxysmal AF, AF is generally considered a progressive disease. In individuals with paroxysmal AF, progression to persistent and permanent AF occurs in >50 percent beyond 10 years despite antiarrhythmic therapy [1].
●Long-standing persistent AF – Long-standing persistent AF refers to persistent AF that has lasted for one year or more [2].
●Permanent AF – Permanent AF is a term used to identify individuals with persistent AF where a decision has been made to no longer pursue a rhythm control strategy.
CATHETER ABLATION AND ANTIARRHYTHMIC DRUG THERAPY
General considerations — Catheter ablation uses either cryoablation (cryotherapy) or radiofrequency ablation (RFA). Pulse-field ablation, another promising energy source, is not yet approved by the United States Food and Drug Administration. AF recurrence, defined as an AF episode >30 seconds in duration on cardiac monitoring, occurs in approximately 20 to 40 percent of patients at one year, although overall AF burden is often markedly decreased [3]. Important complications from catheter ablation include cardiac tamponade (1 percent), pulmonary vein stenosis (<1 percent), phrenic nerve paralysis (up to 3 percent), and rare instances of stroke and atrioesophageal fistula [4-6]. These and other complications are described in detail separately. (See "Atrial fibrillation: Catheter ablation", section on 'Complications'.)
A 2017 randomized comparison between cryoablation and RFA showed similar success rates, as did a meta-analysis of observational studies [7,8]. (See "Atrial fibrillation: Catheter ablation" and "Catheter ablation for the treatment of atrial fibrillation: Technical considerations for non-electrophysiologists".)
Commonly employed drugs to maintain sinus rhythm are amiodarone, sotalol, dofetilide, dronedarone, flecainide, and propafenone. Approximately 25 to 50 percent of people who receive antiarrhythmic medications will have recurrent AF within one year. Important side effects of antiarrhythmics include proarrhythmia, bradyarrhythmia, and organ toxicity in the case of amiodarone. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials".)
Approach — For patients with symptomatic paroxysmal AF in whom a rhythm rather than a rate control strategy is being pursued, either catheter ablation or AAD are reasonable first-line therapies. We suggest catheter ablation as first-line therapy over AAD in younger patients, patients who are poor candidates for AAD therapy, or in those concerned about the potential complications of AADs. Other factors that may impact the safety and efficacy of catheter ablation also need to be considered when deciding between catheter ablation and AAD.
For patients with symptomatic paroxysmal or persistent AF who have failed or become intolerant to one or more AADs, we recommend catheter ablation.
For patients with symptomatic persistent or longstanding persistent AF who have failed or become intolerant of one or more AADs or who choose not to start antiarrhythmic therapy, we suggest catheter ablation.
PATIENTS WITHOUT PRIOR ANTIARRHYTHMIC DRUG TREATMENT — For patients who have chosen rhythm control and who have not previously received antiarrhythmic drug (AAD) therapy, either AAD or CA may be appropriate. All patients need to be informed of the possibility of recurrence of AF and AF-related symptoms and adverse events with both therapies. Recurrence rates and side effects are discussed in detail elsewhere. (See "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Clinical trials" and "Atrial fibrillation: Catheter ablation", section on 'Complications' and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations", section on 'Drug-related arrhythmias and mortality'.)
Until recently, catheter ablation (CA) was generally not offered as first-line therapy given the complexity of the procedure and the potential for complications. It was typically offered to patients who had failed AAD therapy. However, evidence suggests that CA is superior to AAD for control of symptoms. While CA appears superior to AAD for the prevention of AF recurrence, there is no evidence that the rates of cardiovascular death, myocardial infarction, or stroke differ between the two interventions. In addition, in the studies demonstrating superiority of CA, the procedure was performed by highly expert electrophysiologists. Thus, CA by an experienced operator may be considered as first-line therapy for symptomatic patients who, after a full discussion of the benefits and risks of both approaches, prefer an invasive approach.
This section will review the studies that have directly compared the two approaches as first-line therapy. These studies demonstrate that among the advantages of ablation, there is a greater reduction in AF recurrences, progression to persistent AF, and AF-related symptoms.
In a meta-analysis of six studies in 1200 patients comparing CA with AAD as first-line treatment for paroxysmal AF, CA was associated with [9]:
●Lower rates of recurrent atrial arrhythmias (35 versus 53 percent; risk ratio [RR] 0.64, 95% CI 0.51-0.80) [9].
●Similar risks of serious adverse events (18 versus 21 percent; RR 0.87, 95% CI 0.58-1.30). Adverse events were defined differently across studies and included stroke, tamponade, and death.
●Lower rates of symptomatic atrial arrhythmias.
●Lower healthcare resource utilization.
●Lower rates of crossover to alternative treatment (RR 0.21, 95% CI 0.13-0.32).
Limitations of this study include a moderate degree of heterogeneity among the included studies; one study in particular accounted for most of the heterogeneity (the RAAFT 2 trial) [10].
A randomized study of 303 patients (EARLY-AF) compared initial rhythm-control therapy with catheter ablation with antiarrhythmic therapy in individuals with paroxysmal AF [11]. Over 36 months of follow-up the following findings were noted:
●Patients assigned catheter ablation had less persistent AF compared with patients assigned to AADs (1.9 versus 7.4 percent; hazard ratio [HR] 0.25; 95% CI 0.09-0.70).
●Patients assigned catheter ablation had less recurrent atrial tachyarrhythmia, which occurred in 87 patients in the ablation group (56.5 percent) and in 115 in the AAD group (77.2 percent; 56.5 versus 77.2 percent; HR 0.51; 95% CI 0.38-0.67).
●Serious adverse events occurred in seven patients (4.5 percent) in the ablation group and in 15 (10.1 percent) in the AAD group.
Limitations of this study include the sole use of cryoballoon ablation and the exclusion of patients with persistent AF.
PATIENTS WITH PRIOR ANTIARRHYTHMIC DRUG TREATMENT — For patients with either paroxysmal or persistent (see 'Classification' above) AF who seek to reduce their symptom burden and have received treatment with at least one effective antiarrhythmic drug, the option of continuing AAD or undergoing AF ablation should be based on the success and tolerability of AAD therapy along with patient preference. The patient's choice will be guided by advantages and burdens of each approach. (See "Atrial fibrillation: Catheter ablation" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations".)
This section will review the studies that have directly compared the two approaches. These studies suggest that although catheter ablation and antiarrhythmic drug therapy lead to similar rates of all-cause mortality and other serious morbidities, there may be a greater improvement in quality of life with the former.
This topic is not intended to address management in patients who have failed rhythm control with two or more antiarrhythmic drugs or those who have already received catheter ablation. Failure of an antiarrhythmic drug is defined as a drug trial that results in a reduction in AF burden that is not satisfactory to the patient, or results in side effects that are intolerable to the patient, proarrhythmia, or organ toxicity. (See "Atrial fibrillation: Catheter ablation" and "Antiarrhythmic drugs to maintain sinus rhythm in patients with atrial fibrillation: Recommendations", section on 'Long-term issues'.)
Three early meta-analyses of studies comparing catheter ablation and antiarrhythmic drug therapy found that recurrence of AF occurred less often in patients who received catheter ablation in the 12 months after initiation of therapy [12-14]. The following three randomized trials directly compared catheter ablation with antiarrhythmic drug therapy:
●The ThermoCool AF study randomly assigned 167 symptomatic patients with paroxysmal AF (no episodes lasting more than 30 days) who did not respond to at least one AAD and who experienced at least three episodes of paroxysmal AF within six months before randomization to either catheter ablation (with RFA) or AAD therapy in a 2:1 fashion [15]. Patients with significant left ventricular dysfunction, persistent AF, and advanced heart failure were excluded. Catheter ablation included pulmonary vein isolation with confirmation of entrance block, and AAD therapy included flecainide (36 percent), propafenone (41 percent), dofetilide, sotalol, or quinidine at the investigator's discretion. After nine months, there were significantly fewer patients with documented symptomatic paroxysmal AF in the catheter ablation group (16 versus 66 percent; hazard ratio 0.30, 95% CI 0.19-0.47). In addition, major treatment-related adverse events occurred more often with AAD therapy (9 versus 5 percent) at 30 days. Mean quality-of-life scores improved significantly with catheter ablation compared to AAD therapy.
●The STOP AF trial randomly assigned 245 paroxysmal AF patients (in a 2:1 manner) to cryoballoon ablation or drug therapy [16]. Patients had previously failed drug therapy; paroxysmal and early persistent AF were present in 78 and 22 percent, respectively. Treatment success was defined as freedom from chronic treatment failure, as defined by the absence of: any detectable AF after the blanking period; use of a non-study antiarrhythmic drug; and any non-protocol intervention for AF. At 12 months, the primary end point was present in 69.9 and 7.3 percent of the two groups (p<0.001). Serious adverse procedure-related events occurred in 3.1 percent. Phrenic nerve palsy occurred in 11.2 percent, but resolved in the majority.
●The Catheter ABlation vs ANtiarrhythmic Drug Therapy in Atrial Fibrillation (CABANA) trial randomly assigned 2204 patients with paroxysmal (43 percent) or persistent AF (57 percent) to catheter ablation or antiarrhythmic drug therapy [17]. Patients were excluded if they had a prior catheter ablation or had failed two or more antiarrhythmic drugs. The following findings were noted:
•Among the patients who received antiarrhythmic drug therapy, 27.5 percent crossed over to the ablation group.
•The primary composite end point (death, disabling stroke, serous bleeding, or cardiac arrest) occurred in 8.0 and 9.2 percent of the two groups, respectively (hazard ratio [HR] 0.86, 95% CI 0.65-1.15), during a median follow-up of about four years. There was no difference in all-cause mortality (5.2 versus 6.1 percent; HR 0.85, 95% CI 0.60-1.21). The end point of death or cardiovascular hospitalization occurred less often with catheter ablation (51.7 versus 58.1 percent; HR 0.83, 95% CI 0.74-0.93), as did the rate for AF recurrence (49.9 versus 69.5 percent; HR 0.52, 95% CI 0.45-0.60).
•Both patient groups achieved significant improvement in quality-of-life scores, and the improvement in the catheter ablation group was significantly greater than in the drug therapy group. Using one quality-of-life tool, the mean score at baseline was approximately 63 points. At 12 months, the scores were 80.9 and 86.4 points, respectively [18].
●The Catheter Ablation compared with optimized Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial randomly assigned 155 patients with symptomatic persistent or paroxysmal AF to catheter ablation or antiarrhythmic drug therapy [19]. The primary end point, SF-36 General Health score, improved more in the ablation group than the drug therapy group from baseline to 12 months (mean baseline score, 61.8 versus 62.7; mean change 11.9 versus 3.1, respectively; p = 0.003).
Patients with heart failure — Mortality and morbidity are higher among patients with atrial fibrillation and heart failure than among those with heart failure alone. Adverse events due to antiarrhythmic drug therapy appear to be higher in patients with heart failure and reduced ejection fraction. Catheter ablation for atrial fibrillation has been proposed as a means of improving outcomes among patients with heart failure who are otherwise receiving appropriate treatment. This issue is discussed separately. (See "The management of atrial fibrillation in patients with heart failure", section on 'Catheter ablation'.)
RECOMMENDATIONS OF OTHERS — Recommendations for the use of catheter ablation are available in societal guidelines. The 2016 European Society of Cardiology guideline recommends catheter ablation for patients with symptomatic, paroxysmal, persistent, and probably long-standing persistent atrial fibrillation who have failed (or are intolerant to) treatment with at least one antiarrhythmic drug [20].
The 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation makes the following recommendations regarding catheter ablation (CA) to maintain sinus rhythm [21]
●CA is useful for symptomatic paroxysmal AF refractory or intolerant to at least one class I or III antiarrhythmic medication when a rhythm control strategy is desired.
●CA is reasonable for selected patients with symptomatic persistent AF refractory or intolerant to at least one class I or III antiarrhythmic medication.
●CA may be considered for symptomatic long-standing (>12 months) persistent AF refractory or intolerant to at least one class I or III antiarrhythmic medication, when a rhythm control strategy is desired.
●CA may be considered prior to initiation of antiarrhythmic drug therapy with a class I or III antiarrhythmic medication for symptomatic paroxysmal AF when a rhythm control strategy is desired.
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".)
SUMMARY AND RECOMMENDATIONS
●Patients without prior antiarrhythmic drug treatment – For most patients with new-onset symptomatic paroxysmal atrial fibrillation (AF) who have chosen a rhythm rather than a rate control strategy, both antiarrhythmic drug (AAD) therapy or catheter ablation (CA) can be considered as initial therapy (Grade 2C). Patients who may reasonably prefer CA as initial therapy include those who are concerned about the potential complications of AAD or the higher rate of AF recurrence with it. (See 'Patients without prior antiarrhythmic drug treatment' above.)
●Patients with prior antiarrhythmic drug treatment – For patients with symptomatic paroxysmal or persistent AF and who have failed or become intolerant to one or more AAD, we recommend CA (Grade 1A). (See 'Patients with prior antiarrhythmic drug treatment' above.)
For patients with symptomatic persistent or longstanding persistent AF who have failed or become intolerant of one or more AAD or who choose not to start antiarrhythmic therapy, we suggest CA (Grade 2B). (See 'Patients with prior antiarrhythmic drug treatment' above.)
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