Dr Edward P Gerstenfeld

The Antiarrhythmics After Ablation of Atrial Fibrillation (5A) study suggests that such drug therapy aimed at preventing recurrences after AF ablation, which is commonly but not universally done and which is performed differently from practice to practice, can actually work and be well tolerated by patients without an important risk of proarrhythmia or other adverse effects, according to lead investigator Dr Edward P Gerstenfeld (Hospital of the University of Pennsylvania, Philadelphia).

Practices varied before the 5A trial even among the 13 electrophysiologists at his center, Gerstenfeld said. "But everyone [here] now puts people on drugs for that six-week period. I think there were really no data before this. I think now there are clear data [suggesting] that the beneficial effects outweigh the proarrhythmic [risk]."

The 5A trial enrolled patients with paroxysmal AF that hadn't responded to antiarrhythmic therapy before their ablation, Gerstenfeld observed. With the procedure, he said, "some people are completely cured of AF, and there is a group that still requires antiarrhythmic drugs, but now their atrial fibrillation is completely suppressed by drugs that weren't working before."

As reported at the meeting by Dr Jean-Francois Roux (Hospital of the University of Pennsylvania), 5A randomized 110 adults undergoing ablation by pulmonary-vein isolation for paroxysmal AF who had previously demonstrated tolerance to antiarrhythmic therapy and had not been on amiodarone for at least three months. About 70% of the patients were on antiarrhythmic agents at randomization, and about 60% were on class 1C agents, Roux said. The 53 patients assigned to antiarrhythmic therapy started on the drugs the night of the ablation; the 57 in the control group couldn't receive the same kind of therapy unless they developed severe symptomatic AF or atrial arrhythmias lasting at least 24 hours. Antiarrhythmics were given in an unblinded fashion and consisted of class 1C agents in patients without structural heart disease, Roux said; otherwise dofetilide or sotalol was used.

Dr Jean-Francois Roux

Flecainide was the choice in 34% of the patients assigned to antiarrhythmic therapy, propafenone in 26%, sotalol in 36%, and dofetilide in 4%, Roux reported.

Over the trial's six weeks, patients in the antiarrhythmic arm experienced significantly fewer instances of the primary end point, a composite of severe symptomatic atrial arrhythmias, clinically significant atrial arrhythmias lasting >24 hours requiring initiation of or change in drug therapy, hospitalization for arrhythmias or cardioversion, and intolerance of antiarrhythmics requiring their withdrawal or a switch to another agent. Their rate was 17%, compared with 40% in the control group (p<0.01).

The difference, Roux said, was driven by one component of the composite, clinically significant atrial arrhythmias lasting >24 hours requiring initiation of or change in drug therapy. That occurred once in the antiarrhythmic group and 14 times in the control group (p<0.01); there were no significant differences for the other components.

When that end point was slightly expanded to include hospitalization for arrhythmias or cardioversion, the difference was still significant; the rates were 11% in the antiarrhythmic group and 26% in the control group (p<0.05).

Only two adverse events that prompted termination of antiarrhythmics were observed; they were a skin rash and a case of headache with severe fatigue, Roux said.

Other studies suggest that patients who develop atrial arrhythmias in the first six weeks are at increased risk of subsequent recurrences, according to Roux, so the 5A investigators are tracking their patients out to six months and one year. In their trial, he said, "we suspect that early recurrence will be predictive of longer-term risk of recurrence."