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

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.

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.