Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation - MANTRA-PAF


The goal of the trial was to evaluate an initial strategy of radiofrequency catheter ablation compared with antiarrhythmic drug therapy among patients with paroxysmal atrial fibrillation.

Contribution to the Literature: The MANTRA-PAF trial showed that pulmonary vein isolation was superior to antiarrhythmic drug use in reducing atrial fibrillation burden at 5 years in patients with symptomatic paroxysmal atrial fibrillation.

Study Design

  • Randomized
  • Blinded
  • Parallel
  • Stratified

Patient Populations:

  • Patients with at least two episodes of symptomatic paroxysmal atrial fibrillation within the last 6 months and no history of antiarrhythmic drug therapy

    Number of enrollees: 294
    Duration of follow-up: 24 months
    Mean patient age: 56 years
    Percentage female: 32%
    Ejection fraction: >60% in 79%; 40-60% in the remainder
    New York Heart Association class: I-90%, II-10%


  • Age >70 years
  • Previous or ongoing treatment with antiarrhythmic drug therapy
  • Contraindication to antiarrhythmic drug therapy
  • Prior radiofrequency catheter ablation
  • Left atrial diameter >50 mm
  • Left ventricular ejection fraction <40%
  • Contraindication to oral anticoagulation therapy
  • Moderate to severe mitral valve disease
  • Severe heart failure
  • Expected surgery for structural heart disease
  • Atrial fibrillation due to surgery, infection, or hyperthyroidism

Primary Endpoints:

  • Burden of atrial fibrillation, defined as the percentage of time in atrial fibrillation on each Holter recording and the percentage of time in atrial fibrillation on all Holter recordings

Secondary Endpoints:

  • Freedom from any atrial fibrillation at 24 months
  • Freedom from symptomatic atrial fibrillation at 24 months
  • Quality of life
  • Serious adverse events

Drug/Procedures Used:

Patients with symptomatic paroxysmal atrial fibrillation and no history of antiarrhythmic drug therapy were randomized to radiofrequency catheter ablation (n = 146) versus antiarrhythmic drug therapy (n = 148).

Prior to radiofrequency catheter ablation, patients were treated with anticoagulation therapy (international normalized ratio [INR] >2.0) for at least 3 weeks. Transesophageal echocardiography was performed prior to the procedure to evaluate for left atrial thrombi. After ablation, patients could be treated with antiarrhythmic drug therapy for 3 months.

Patients in the antiarrhythmic drug therapy group could receive a class IC agent (flecainide 200 mg daily or propafenone 600 mg daily). A class III agent (amiodarone 200 mg daily or sotolol 160 mg daily) could be used if a class IC agent was contraindicated. Direct-current cardioversion could be used as needed to maintain sinus rhythm.

Concomitant Medications:

Before randomization: warfarin (45%), beta-blockers (73%), digoxin (11%), calcium channel blockers (15%)

Principal Findings:

Overall, 294 patients were randomized. The mean age was 56 years, 32% were women, mean body mass index was 27 kg/m2, and 29% had hypertension.

The ablation group underwent a mean of 1.6 procedures per patient. In the drug therapy group, 99% of patients received a class IC antiarrhythmic. Thirty-six percent of patients crossed over to receive radiofrequency ablation. Quality of life improved in both groups.

Atrial fibrillation was reduced by a similar amount in both groups at the 3-, 6-, 12-, and 18-month follow-up visits. At the 24-month follow-up visit, burden of atrial fibrillation was reduced with radiofrequency catheter ablation compared with antiarrhythmic drug therapy: 9% versus 18% (p = 0.007), respectively. However, the cumulative atrial fibrillation burden was similar between groups (p = 0.1).

- Freedom from any atrial fibrillation: 85% vs. 71% (p = 0.004)
- Freedom from symptomatic atrial fibrillation: 93% vs. 84% (p = 0.01)
- Death: 3 vs. 4
- Stroke/TIA: 2 vs. 1
- Tamponade: 3 vs. 0
- Pulmonary vein stenosis: 1 vs. 0

Five-year follow-up: Additional ablations were necessary in 27 vs. 22 patients in the pulmonary vein isolation vs. antiarrhythmic drug arms. Atrial fibrillation burden was still lower in the pulmonary vein isolation arm compared with the antiarrhythmic drug arm (p = 0.003). Similarly, on a 7-day Holter monitor at 5 years, freedom from atrial fibrillation (86% vs. 71%, p = 0.001) and freedom from symptomatic atrial fibrillation (94% vs. 85%, p = 0.015) were lower in the pulmonary vein isolation arm. Quality-of-life metrics were similar between the two strategies at 5 years.


Among patients with paroxysmal atrial fibrillation, first-line treatment with radiofrequency catheter ablation did not reduce the cumulative burden of atrial fibrillation compared with antiarrhythmic drug therapy. Due to the inherent risks of radiofrequency catheter ablation, antiarrhythmic drug therapy remains first-line treatment for paroxysmal atrial fibrillation. Older patients, those with severe heart failure, or individuals with persistent/permanent atrial fibrillation were not represented in this trial. It is unknown if newer techniques of radiofrequency catheter ablation would have resulted in a different outcome.

Results appear durable at 5 years. Quality-of-life assessments also favored pulmonary vein isolation at 2 years, and were similar between the two arms at 5 years.


Presented by Dr. Jens Cosedis Nielsen at the European Society of Cardiology Congress, London, September 1, 2015.

Nielsen JC, Johannessen A, Raatikainen P, et al. Radiofrequency Ablation as Initial Therapy in Paroxysmal Atrial Fibrillation. N Engl J Med 2012;367:1587-95.

Presented by Dr. Jens Cosedis Nielsen at the American Heart Association Scientific Sessions, Orlando, FL, November 14, 2011.

Clinical Topics: Arrhythmias and Clinical EP, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Prevention, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Acute Heart Failure, Echocardiography/Ultrasound, Hypertension

Keywords: Stroke, Follow-Up Studies, Pulmonary Veins, Electric Countershock, Constriction, Pathologic, Cost of Illness, International Normalized Ratio, Body Mass Index, Quality of Life, Heart Failure, Propafenone, Flecainide, Catheter Ablation, Hypertension, Echocardiography, Transesophageal, Atrial Flutter

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