Catheter Ablation Versus Antiarrhythmic Drugs for Atrial Fibrillation - A4 Study


The goal of the trial was to evaluate catheter ablation compared with antiarrhythmic drug therapy among patients with atrial fibrillation (AF).


Catheter ablation for AF will be superior to pharmacological therapy for maintaining sinus rhythm.

Study Design

  • Randomized
  • Parallel

Patients Screened: 149
Patients Enrolled: 112
Mean Follow Up: 12 months
Mean Patient Age: 51 years
Female: 16
Mean Ejection Fraction: 64%

Patient Populations:

  • Symptomatic paroxysmal AF over a span of at least 6 months with two episodes during the preceding month
  • Age >18 years
  • Resistant to at least one antiarrhythmic drug


  • Contraindication to >2 antiarrhythmic drugs in two different classes or contraindication to anticoagulation
  • Prior AF ablation
  • Intracardiac thrombus
  • Reversible AF
  • Pregnancy

Primary Endpoints:

  • Proportion of patients free of recurrent AF between months 3 and 12

Secondary Endpoints:

  • Time to recurrent atrial fibrillation
  • Complications and adverse events
  • Change in myocardial dimensions and function
  • Quality of life
  • Exercise capacity
  • AF burden
  • Efficacy of amiodarone when used for the first time

Drug/Procedures Used:

Patients were randomized to catheter ablation (n = 53) or antiarrhythmic drug therapy (n = 59) with one of six medications. After the primary endpoint was assessed at 3 months, patients could cross over from medical therapy to ablation, and would be counted as having met the endpoint.

Concomitant Medications:

Before enrollment, 87% of participants had used a class 1 antiarrhythmic drug, 65% had used a class 2 agent, 75% had used a class 3 agent, and 10% had used a class 4 agent.

Principal Findings:

At baseline, the median number of AF episodes per month was 12, lasting a median of 5.5 hours. Structural heart disease was present in 26% of patients. The mean left atrial dimension in the parasternal long axis was 40 mm. In the ablation group, the mean procedure duration was 168 minutes, and an average of 1.8 procedures were performed. Crossover to the other therapy occurred in 9% of the ablation group and 63% of the drug group.

At 1 year, 89% of patients in the ablation group and 23% in the medical therapy group were free of arrhythmic recurrence (p

Among the quality-of-life parameters, six of eight were significantly improved in the ablation group. Among all patients treated with ablation in the trial (n = 90 patients and 155 procedures), including crossovers, there were two cases of tamponade and two cases of groin hematoma.


Among patients with AF, catheter ablation was associated with higher rates of absence of AF compared with antiarrhythmic drug therapy at 1 year.

One limitation of the trial was the short duration of AF needed to meet the primary endpoint—only 3 minutes. Additionally, it should be noted that patients in the trial had all previously failed antiarrhythmic drug therapy, and results may not be applicable to other AF patients who had not failed therapy or patients who are not symptomatic.


Jais P, Cauchemez B, Macle L, et al. Catheter ablation versus antiarrhythmic drugs for atrial fibrillation. The A4 Study. Circulation 2008;118:2498-505.

Presented by Pierre Jais, MD, at the Heart Rhythm Society Annual Scientific Sessions, Boston, MA, May 2006.

Clinical Topics: Arrhythmias and Clinical EP, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Recurrence, Hematoma, Catheter Ablation, Groin

< Back to Listings