Radiofrequency Ablation (RFA) Versus Antiarrhythmic Drug Treatment in Paroxysmal Atrial Fibrillation
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Study type: Interventional
Phase: Phase 3

Summary: 
      Atrial fibrillation is the most common heart arrhythmia afflicting approximately 1% of the
      Danish population. Medical antiarrhythmic treatment is only moderately effective and has the
      risk of severe side effects. The present study is a prospective, randomized, multicentre
      study comparing medical antiarrhythmic drug strategy with catheter based radiofrequency
      strategy in patients with paroxysmal atrial fibrillation. The primary end point is atrial
      fibrillation burden (symptomatic and asymptomatic) judged by multiple 7-day Holter
      monitorings during 2 years follow-up. Three hundred patients considered candidates for
      antiarrhythmic drug treatment will be randomized. The study will be performed as a
      Scandinavian/German multicentre study.
    

Detailed description: 
      Introduction:

      Atrial fibrillation is by far the most common heart arrhythmia and is even increasing in
      prevalence and incidence. Approximately 10% of all cardiologic hospitalizations are due to
      atrial fibrillation. Several studies have shown older patients with paroxysmal or persistent
      atrial fibrillation and with minor symptoms related to the arrhythmia do equally well on a
      frequency control as compared to a rhythm control strategy. However, some of this lack of
      difference in outcome may be because the benefits by achieving sinus rhythm are outbalanced
      by the risk of medication with presently known antiarrhythmic drugs together with the only
      modest efficacy of these drugs. Non-pharmacological treatment of atrial fibrillation has
      drawn increasing interest over the last decade, and especially percutaneous catheter based
      ablation strategies have been in focus with promising results on the symptomatic level in
      several series of patients. Different technologies have been in use with very few comparative
      studies. Most important, no study has been published so far on a consecutive series of
      patients with atrial fibrillation randomized to either a pharmacological or an ablative
      strategy. Also important is that the majority of studies have been single-centre based prone
      to a multitude of potential selection biases.

      Hypothesis:

      Pulmonary vein isolation by transvenous radiofrequency ablation is superior to present time
      antiarrhythmic drug therapy with regard to long-term suppression of atrial fibrillation
      (symptomatic and asymptomatic) as well as to procedure/treatment related side effects.

      Purpose:

      The present study is designed to test whether catheter based radiofrequency ablation is
      superior to optimized antiarrhythmic medical therapy in suppressing long-term relapse of
      symptomatic and/or asymptomatic atrial fibrillation in patients who are not already in
      chronic pharmaceutical antiarrhythmic therapy. Secondary end points are: mortality,
      thromboembolic events, hospitalization due to disturbance in heart rhythm, proarrhythmic
      events, procedure/treatment related side effects, health economics and quality of life.
      Comparison will be made after two years follow-up and a register follow-up will take place
      after additional 3 years (a total of at least five years of follow-up).

      Consecutive patients fulfilling the inclusion criteria will be informed about the study by a
      study-responsible electrophysiologist or his/her substitute. After informed consent the
      patient will be randomized to either antiarrhythmic drug treatment or to catheter ablation.
      All patients undergo transthoracic echocardiography before randomization.

      A register of all patients informed about (i.e. fulfilling the inclusion criteria) but for
      one or more reasons not included in the study will be established.

      Primary endpoint:

      Atrial fibrillation burden (see below), symptomatic and asymptomatic combined. Atrial
      fibrillation burden will be calculated from one-week Holter monitoring at 3, 6, 12, 18 and 24
      months, respectively, after treatment (first RF-procedure or AAD-initiation).

      Secondary endpoints:

        -  Mortality

        -  Complications (including thromboembolic events, major bleeding episodes, pro-arrhythmic
           events, and treatment related side effects)

        -  QOL

        -  Health economics (including number of DC-conversions, cardiovascular hospitalizations
           (type, length and number of antiarrhythmic drugs))

        -  Chronic atrial fibrillation (constant atrial fibrillation during one-week Holter
           monitoring at 24 months follow-up, together with atrial fibrillation during the
           immediately foregoing 8 weeks)

        -  Time to first recurrence (after 3 months blanking period)

        -  Left ventricular systolic function (transthoracic echo)
    

Intervention name(s): Radiofrequency ablation
Intervention type(s): Procedure
Intervention description(s): Pulmonary vein isolation
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Paroxysmal atrial fibrillation; Heart arrhythmia; Ablation; Drug treatment