RAAFT-2: Radiofrequency Ablation vs. Antiarrhythmic Drugs as First-Line Treatment of Paroxysmal Atrial Fibrillation

Editor’s Note: Commentary based on Morillo CA, Verma A, Connolly SJ, et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial. JAMA 2014;311:692-700.


The Radiofrequency Ablation vs Antiarrhythmic Drugs as First-Line Therapy of Atrial Fibrillation 2 (RAAFT-2) trial1 evaluated whether catheter ablation of atrial fibrillation (AF) was superior to antiarrhythmic drugs as first-line therapy in patients with paroxysmal atrial fibrillation (PAF) who had not been exposed to antiarrhythmic treatment. The 2012 Heart Rhythm Society (HRS), European Heart Rhythm Association (EHRA), and European Cardiac Arrhythmia Society (ECAS) guidelines2 on catheter ablation of AF provide a Class 1, Level of Evidence A recommendation for catheter ablation of AF for patients with PAF after failure of at least one antiarrhythmic medication and a Class 2, Level of Evidence B recommendation for ablation as first line therapy. Two previous studies have addressed the question of AF ablation versus antiarrhythmic medications as first line therapy. The RAAFT-1 randomized trial published in 2005 by Wazni et al.,3 enrolled 70 patients and showed that ablation was superior to antiarrhythmic drug therapy with AF recurrence rates of 63% in the antiarrhythmic drug group versus 13% in the catheter ablation group at 12 months of follow-up (P <0.001). The Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial published in 2012 by Nielsen et al.4 enrolled 294 patients and demonstrated no difference in cumulative AF burden during two years of follow-up, as assessed with seven-day Holter monitors at three- to six-month intervals. Despite the absence of a difference in cumulative AF burden, at 24 months of follow-up the AF burden was lower in patients randomized to ablation (9% vs. 18%, P = 0.007) and more patients in the ablation group were AF free. Ablation also had a significant advantage for the secondary end point of freedom from symptomatic AF at 24 months (P = 0.01). In addition, more than one-third of drug-treated patients crossed over to ablation during the follow-up, usually in the first year. Complications in the ablation group included one death due to a stroke and three cases of cardiac tamponade. Quality of life improved in both treatment groups.


RAAFT-2 was a randomized clinical trial involving 127 treatment-naïve patients with paroxysmal AF from 16 centers in Europe and North America who received either antiarrhythmic therapy (n = 61) or catheter ablation (n = 66) and were followed for 24 months. The primary outcome was the time to the first documented atrial tachyarrhythmia of more than 30 seconds (symptomatic or asymptomatic AF, atrial flutter, or atrial tachycardia), starting after a 90-day blanking period and detected by either scheduled or unscheduled electrocardiogram, Holter, transtelephonic monitor, or rhythm strip. Secondary outcomes included symptomatic recurrences of atrial tachyarrhythmias and quality of life measures assessed by the EQ-5D tool. Cox regression analysis was used to generate hazard ratios for arrhythmia recurrence and event-free survival curves were generated using Kaplan-Meier plots.


Forty-four patients (72.1%) in the antiarrhythmic group and 36 patients (54.5%) in the ablation group experienced the primary efficacy outcome (hazard ratio [HR], 0.56 [95% CI, 0.35-0.90]; P = 0.02). For the secondary outcomes, 59% in the drug group and 47% in the ablation group experienced the first recurrence of symptomatic AF, atrial flutter, atrial tachycardia (HR, 0.56 [95% CI, 0.33-0.95]; P = 0.03). No deaths or strokes were reported in either group; the overall complication rate was 9% and four cases (6%) of cardiac tamponade were reported in the ablation group. In the medical treatment group, 26 patients (43%) underwent ablation after one year, and six patients (9%) in the ablation group received antiarrhythmic therapy during follow-up. Quality of life was moderately impaired at baseline in both groups and improved at the one-year follow-up. However, improvement was not significantly different among groups.


The authors concluded that among patients with paroxysmal AF without previous antiarrhythmic drug treatment, radiofrequency ablation compared with antiarrhythmic drugs resulted in a lower rate of recurrent atrial tachyarrhythmias at two years, but asymptomatic and symptomatic recurrence was frequent in both groups.


This small (n = 127) randomized trial demonstrated that catheter ablation was superior to antiarrhythmic drugs for the prevention of atrial tachyarrhythmias over two years of follow-up. Ablation was also superior to antiarrhythmic drugs in terms of symptomatic arrhythmia recurrence. There was modest improvement in quality of life at one year in both treatment groups, but no difference between the treatment arms. However, the rates of any atrial tachyarrhythmia recurrence were high relative to previous studies evaluating this question (54.5% for ablation vs. 72% for the antiarrhythmic group). The complication rate of catheter ablation was also higher in this trial than in previous studies, with a 9% overall complication rate and a 6% incidence of cardiac tamponade.

The results of this study are important for a number of reasons. The results are generally consistent with previous studies in showing a modest but significant advantage to catheter ablation as first-line therapy for maintenance of sinus rhythm in patients with paroxysmal AF. However, the intensive biweekly transtelephonic monitoring performed in this study showed much lower rates of freedom from AF than have previously been reported,5,6 which demonstrates that atrial arrhythmia recurrences are common with both therapeutic modalities. In addition, the complication rates with the procedure in this study were higher than previously reported, which serves as a reminder that the procedure may be associated with some substantial risk even in the hands of experienced operators. The choice of antiarrhythmic drug therapy or catheter ablation for the first-line treatment of AF must, therefore, be individualized to each patient depending on their treatment goals and risk tolerance.


  1. Morillo  CA, Verma  A, Connolly  SJ,  et al.  Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of paroxysmal atrial fibrillation (RAAFT-2): a randomized trial. JAMA 2014;311:692-700.
  2. Calkins  H, Kuck  KH, Cappato  R,  et al. Heart Rhythm Society Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Heart Rhythm 2012;9:632-96. e21.
  3. Wazni  OM, Marrouche  NF, Martin  DO,  et al. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA 2005;293:2634-40.
  4. Cosedis Nielsen  J, Johannessen  A, Raatikainen  P,  et al. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. N Engl J Med 2012;367:1587-95.
  5. Cappato  R, Calkins  H, Chen  SA,  et al. Updated worldwide survey on the methods, efficacy, and safety of catheter ablation for human atrial fibrillation. Circ Arrhythm Electrophysiol 2010;3:32-8.
  6. Deshmukh  A, Patel  NJ, Pant  S,  et al. In-hospital complications associated with catheter ablation of atrial fibrillation in the United States between 2000 and 2010: analysis of 93 801 procedures. Circulation 2013;128:2104-12.

Clinical Topics: Arrhythmias and Clinical EP, Pericardial Disease, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Anti-Arrhythmia Agents, Arrhythmias, Cardiac, Atrial Fibrillation, Atrial Flutter, Cardiac Tamponade, Catheter Ablation, Disease-Free Survival, Electrocardiography, Europe, North America, Quality of Life, Tachycardia

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