Inclusion Criteria:

• Over the preceding 6 months have:
  1. ≥2 paroxysmal (electrocardiographic documentation of at least 1) AF episodes lasting ≥1 hour in duration: (that terminate spontaneously within 7 days or cardioversion is performed within 48h of AF onset): or
  2. electrocardiographic documentation of 1 persistent AF episode: (sustained for ≥7 days or cardioversion is performed more than 48h after AF onset): or
  3. electrocardiographic documentation of 1 longstanding persistent AF episode: (continuous AF of duration >1 year).
• Warrant active therapy (within the past 3 months) beyond simple ongoing observation
• Be eligible for catheter ablation and ≥2 sequential rhythm control and/or ≥2 rate control drugs.
• Be ≥65 yrs of age, or <65 yrs with one or more of the following risk factors for stroke: Hypertension (treated and/or defined as a BP >140/90 mmHg) [90], Diabetes (treated and/or defined as a fasting glucose ≥126 mg/dl) [91], Congestive heart failure (including systolic or diastolic heart failure), Prior stroke, TIA or systemic emboli, Atherosclerotic vascular disease (previous MI, peripheral arterial disease or aortic plaque), LA size >5.0 cm (or volume index ≥40 cc/m2), or EF ≤35.
• Have the capacity to understand and sign an informed consent form.
• Be ≥18 years of age.
  • NOTE- Subjects <65 yrs of age whose only risk factor is hypertension must have a second risk factor or LV hypertrophy to qualify.Patients receiving new drug therapy initiated within the previous 3 months may continue that therapy if randomized to the drug therapy arm. Patients may have documented atrial flutter in addition to atrial fibrillation and remain eligible for enrollment.

Exclusion Criteria:

• Lone AF in the absence of risk factors for stroke in patients <65 years of age
• Patients who in the opinion of the managing clinician should not yet receive any therapy for AF
• Patients who have failed >2 membrane active anti-arrhythmic drugs at a therapeutic dose due to inefficacy or side effects (Table 5.2.2)
• An efficacy failure of full dose amiodarone treatment >8 weeks duration at any time
• Reversible causes of AF including thyroid disorders, acute alcohol intoxication, recent major surgical procedures, or trauma
• Recent cardiac events including MI, PCI, or valve or bypass surgery in the preceding 3 months
• Hypertrophic obstructive cardiomyopathy (outflow track)
• Class IV angina or Class IV CHF (including past or planned heart transplantation)
• Other arrhythmias mandating anti-arrhythmic drug therapy (i.e. VT, VF)
• Heritable arrhythmias or increased risk for torsade de pointes with class I or III drugs
• Prior LA catheter ablation with the intention of treating AF
• Prior surgical interventions for AF such as the MAZE procedure
• Prior AV nodal ablation
• Patients with other arrhythmias requiring ablative therapy
• Contraindication to appropriate anti-coagulation therapy
• Renal failure requiring dialysis
• Medical conditions limiting expected survival to <1 year
• Women of childbearing potential (unless post-menopausal or surgically sterile)
• Participation in any other clinical mortality trial (Participation in other non-mortality trials should be reviewed with the clinical trial management center)
• Unable to give informed consent
  • NOTE- Prior ablation of the cavo-tricuspid isthmus alone is not an exclusion if the patient develops subsequent recurrent AF. Planned atrial flutter ablation in combination with the left atrial ablation is not an exclusion.