Early Aggressive Invasive Intervention for Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice, affecting approximately 1-2% of the overall population. Contemporary guidelines recommend AADs as the "first-line" therapy for the maintenance of sinus rhythm. However, these medications have only modest efficacy at maintaining sinus rhythm. Moreover, these agents are associated with significant non-cardiac side-effects, as well as the potential for pro-arrhythmia, heart failure, or organ toxicity. Conversely, the success rate of catheter ablation in maintaining sinus rhythm is universally superior to that of drug therapy when AADs have been ineffective, are contra-indicated, or cannot be tolerated. While catheter ablation has not been definitively proven to improve survival, it has been shown to be superior to AADs for the improvement of symptoms, exercise capacity, and quality of life.

Why consider early invasive intervention? Given the superiority of ablation over AAD therapy, it is postulated that early invasive intervention with catheter ablation offers an opportunity to halt the progressive pathophysiological and anatomical changes associated with AF. While catheter ablation has not been definitively proven to impact mortality in unselected patients, there are certain patient groups (e.g. younger patients, those with newly diagnosed AF, and those with heart failure) who may derive significant benefit from ablation. In addition, early invasive intervention may result in a significant reduction in overall health care utilitization.

The evidence supporting "first-line" catheter ablation (i.e. as an initial therapy prior to AAD) with radiofrequency (RF) energy is promising, but far from definitive. To date three key studies have been performed. The MANTRA-PAF Study and the RAAFT studies randomized patients to either first-line ablation or first-line AADs. Despite disparate ablation techniques, these studies collectively demonstrated an improved freedom from recurrent arrhythmia (37% reduction in AF recurrence vs. AAD therapy), an improved freedom from symptomatic AF (43% reduction in symptomatic AF vs. AAD therapy), and a reduction in the overall AF burden (50% reduction over AAD therapy). While the results of these previous studies suggest that ablation is more effective than AAD therapy as first-line treatment, a significant proportion of patients in the intervention group experienced arrhythmia recurrence.

STUDY DESIGN - The study is a multicenter prospective, open label randomized clinical trial with blinded adjudication of endpoints. Patients with untreated AF will be randomized in a 1:1 ratio to either first-line antiarrhythmic therapy or first-line AF ablation using cryothermal energy. Randomization will be performed with concealed allocation using permuted block randomization according to a computer-generated sequence (Dacima, Montreal, Canada). An independent, blinded statistician will generate the block randomization scheme. Outcomes will be adjudicated by personnel who are blinded to subjects' randomization status.

FUNDING The EARLY-AF study is funded by a peer-reviewed grant from the Cardiac Arrhythmia Network of Canada. In addition, the trial is supported by an unrestricted grant from Medtronic. The funding sources had no role in the design of this study and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results.