Drug therapy should remain the first-line treatment for most patients with paroxysmal atrial fibrillation (AF), researchers advised in a study published Oct. 25 in the New England Journal of Medicine. Based on the results, catheter ablation also offers a reasonable option, according to the authors of an accompanying editorial.
Jens Cosedis Nielsen, MD, of Aarhus University Hospital in Aarhus, Denmark, and colleagues evaluated the long-term efficacy of radiofrequency catheter ablation compared with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal AF. In a multicenter, randomized trial—the Medical Antiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial—they enrolled 294 patients with symptomatic paroxysmal AF between 2005 and 2009.
To be included in the study, patients needed to have no history of antiarrhythmic drug use and at least two episodes of symptomatic AF within the preceding six months and have no episodes lasting beyond seven days. All patients were 70 years old or younger. The patients were randomized to one of two treatments: radiofrequency catheter ablation (146 patients) or therapy using class IC or class III antiarrhythmic agents (148 patients). All ablation patients could receive antiarrhythmic drugs during the first three months after their procedures.
Clinical follow-ups using seven-day Holter monitors occurred at three, six, 12, 18 and 48 months. The primary endpoints included cumulative and per-visit burden of AF, which was defined as the percentage of time in AF as detected on Holter readings. The researchers also assessed freedom from AF at 24 months. Treatment groups were compared on an intention-to-treat basis.
The mean age of patients was 55 and 70 percent were male. In the ablation group, 58 patients underwent two procedures; eight patients had three procedures and three patients had four. In the drug group, 54 patients received supplementary ablation.
Both groups had significantly lower AF burden at each follow-up visit and there was no difference in cumulative burden between the groups or in the number of adverse events.
But at 24 months, AF burden was significantly lower in the ablation group. Eighty-five percent of the ablation group was free of any AF at 24 months compared with 71 percent of the drug therapy group, and 93 percent of the ablation groups was symptomatic AF-free compared with 84 percent of the drug therapy group.
Based on their finding of no difference in cumulative burden between the two strategies over 24 months, and because ablation holds some risk of complications, the authors recommended antiarrhythmic therapy as first-line treatment for most paroxysmal AF patients. They noted that guidelines in the U.S., Europe and Canada also call for this approach.
“However, some advantages of ablation were suggested by our data,” they wrote. Citing the 24-month results, they suggested that ablation may be more durable than drugs. “Furthermore, 36 percent of patients initially assigned to antiarrhythmic drug therapy eventually underwent ablation for recurrent atrial fibrillation (most of them during the first year). This finding suggests that even though an initial strategy of drug treatment is appropriate, a substantial minority of patients so treated may eventually require ablation for adequate rhythm control.”
They noted that more extensive monitoring might have detected more AF episodes but might have placed a burden on patients. Current ablation practice uses newer techniques than were called for in the study, and the study population was relatively young. They cautioned that the findings apply only to younger patients and not those older than 70.
In an accompanying editorial, William G. Stevenson, MD, and Christine M. Albert, MD, both of Brigham and Women’s Hospital in Boston, added that the ablation procedures in the study were performed by experienced operators and in broader clinical practice the outcomes might be different. But they also highlighted the benefits found by Nielsen et al.
“[B]y two years, a greater benefit of ablation began to emerge, with 85 percent of patients free of atrial fibrillation in the ablation group as compared with 71 percent in the drug therapy group,” Stevenson and Albert wrote. “Furthermore, 36 percent of patients in the drug therapy group had crossed over to receive ablation, whereas only 9 percent of patients in the ablation group were receiving antiarrhythmic drugs.”
The trial did not show ablation to be superior to drug therapy, they concluded, but both strategies are reasonable choices for patients who want sinus rhythm maintained, provided physicians and patients weigh the risks and benefits.