Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial

The (Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial) CABANA Trial has the overall goal of establishing the appropriate roles for medical and ablative intervention for atrial fibrillation (AF). The CABANA Trial is designed to test the hypothesis that the treatment strategy of left atrial catheter ablation for the purpose of eliminating atrial fibrillation (AF) will be superior to current state-of-the-art therapy with either rate control or rhythm control drugs for decreasing the incidence of the composite endpoint of total mortality, disabling stroke, serious bleeding, or cardiac arrest in patients with untreated or incompletely treated AF.

The need for this trial arises out of 1) the rapidly increasing number of pts \> 60 years of age with AF accompanied by symptoms and morbidity, 2) the failure of anti-arrhythmic drug therapy to maintain sinus rhythm and reduce mortality, 3) the rapidly increasing application of radio-frequency catheter ablation without appropriate evidence-based validation, and 4) the expanding impact of AF on health care costs.

This study will randomize up to 2200 patients to a strategy of catheter ablation versus pharmacologic therapy with rate or rhythm control drugs. Each pt will have 1) characteristics similar to AFFIRM pts (≥65 yo or \<65 with \>1 risk factor for stroke, 2) Documented AF warranting treatment, and 3) Eligibility for both catheter ablation and ≥2 anti-arrhythmic or ≥2 rate control drugs. Pts will be followed every 6 months for an average of approximately 5 years and will undergo repeat trans-telephonic monitor, Holter monitor, and CT/MR studies to assess the impact of treatment.

The CABANA trial will disclose the role of medical and non-pharmacologic therapies for AF, establish the cost and impact of therapy on quality of life and will help determine if AF is a modifiable risk factor for increased mortality.

Eligibility Criteria:
Inclusion Criteria:

* Over the preceding 6 months have:

  1. ≥2 paroxysmal (electrocardiographic documentation of at least 1) atrial fibrillation (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 blood pressure \>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, transient ischemic attack or systemic emboli, Atherosclerotic vascular disease (previous myocardial infarction (MI), peripheral arterial disease or aortic plaque), left atrial (LA) size \>5.0 cm (or volume index ≥40 cc/m2), or ejection fraction (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 left ventricular (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, percutaneous intervention (PCI), or valve or bypass surgery in the preceding 3 months
* Hypertrophic obstructive cardiomyopathy (outflow track)
* Class IV angina or Class IV congestive heart failure (CHF) (including past or planned heart transplantation)
* Other arrhythmias mandating anti-arrhythmic drug therapy (i.e. ventricular tachycardia (VT), ventricular fibrillation (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.