AARHUS, DENMARK. The battle continues between proponents of antiarrhythmic drugs and catheter ablation as first-line treatment for paroxysmal atrial fibrillation (PAF). At present, it would appear that a trial of one antiarrhythmic drug is warranted before proceeding with ablation. It is hoped that the large CABANA trial now enrolling participants will result in a firm recommendation as to first-line treatment. In the meantime, it is worth pondering the results of the MANTRA-PAF clinical trial which involved 294 patients with PAF treated at centers in Denmark, Finland, Sweden and Germany.
The average age of the patients was 55 years, 70% were male, 7% had structural heart disease or coronary artery disease, and average left atrial diameter was 40 mm. The study participants, none of whom had undergone ablation or been treated with antiarrhythmics prior to enrolment, were randomized into two groups – the radio frequency catheter ablation group (146 patients) and the rhythm-control group (148 patients).
Members of the ablation group underwent an average of 1.6 anatomically-guided pulmonary vein isolation procedures with an additional left atrium roof line and tricuspid isthmus (right atrial flutter) ablation as required. At the 24-month follow-up, 9% of the ablation group members were receiving antiarrhythmic drug therapy. Patients in the rhythm-control group were initially treated with 200 mg/day of flecainide or 600 mg/day of propafenone or, in case this was contraindicated, with 200 mg/day of amiodarone or 160 mg/day of sotalol.
If the initially assigned drug therapy failed, more aggressive drug therapy (amiodarone?), cardioversion or catheter ablation was allowed. Fifty-four patients (36%) in the rhythm-control group underwent a mean of 1.6 ablation procedures with the first taking place about 9 months following inclusion in the study. NOTE: The final study results were based on intention-to-treat; in other words, even though 36% of the group had undergone a mean of 1.6 ablation procedures, they were still considered to be part of the rhythm-control group when comparing the efficacy of ablation and rhythm control.
The burden of AF (percent time spent in AF) was measured via 7-day Holter monitoring at 3, 6, 12, 18 and 24 months. The AF burden was not significantly different in the two groups at 6, 12, and 18 months (13% in ablation group and 19% in rhythm-control group); however, at 24 months the ablation group fared significantly better at 9% vs 18%. At 24 months, 85% of patients in the ablation group were in normal sinus rhythm (NSR) as compared to 71% in the rhythm-control group. However, as mentioned above, these numbers are based on intention-to-treat. In actual fact, at the 2-year follow-up, 76% of the ablation group patients were in NSR without the use of antiarrhythmics, whilst only 35% of those in the rhythm-control group were in NSR without having undergone 1 or more ablations.
Serious adverse events possibly related to AF therapy occurred in 11% of patients in the ablation group vs 8% in the rhythm-control group. One death from stroke, probably related to the procedure was observed in the ablation group. The authors conclude that an initial strategy of ablation as compared with rhythm control showed no significant difference in the cumulative burden of AF over a period of 2 years. NOTE: The list of potential conflicts of interest between the authors and ablation equipment and drug manufacturers is extensive.
Nielsen, JC, et al. Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation. New England Journal of Medicine, Vol. 367, October 25, 2012, pp. 1587-95
Stevenson WG and Albert, CM. Catheter ablation for paroxysmal atrial fibrillation. New England Journal of Medicine, Vol. 367, October 25, 2012, pp. 1648-49 (editorial)
Editor's comment: This clinical trial clearly highlights the problem of reporting results on an intention-to-treat basis. In other words, ignoring the fact that 9% of the ablation group members were on antiarrhythmics and 36% of the rhythm-control group had undergone one or more ablations at the final follow-up. It is clear from the trial, based on a 2-year follow-up, that radio frequency catheter ablation is a better first-line treatment strategy than rhythm control. However, trying an antiarrhythmic drug before deciding on an ablation is still a viable option in view of the current, rapidly evolving ablation techniques.