Boston, MA - Randomized data from a clinical trial presented here at the Heart Rhythm Society 2006 Scientific Sessions provide further support for catheter ablation rather than antiarrhythmic drug therapy for the treatment of paroxysmal atrial fibrillation (AF) [1]. In a cohort of patients who previously failed at least one antiarrhythmic drug, significantly more patients undergoing ablation were free from the arrhythmia at one year compared with those who continued with another antiarrhythmic drug.

"These are patients with paroxysmal atrial fibrillation, who have had at least one or two episodes of atrial fibrillation per month," Dr Pierre Jais (Hôpital Cardiologique Haut-Leveque, Bordeaux-Pessac, France) told heartwire. "They are patients who have failed at least one antiarrhythmic drug therapy, so this is really not a comparison between the two therapies—ablation or antiarrhythmic drugs—as first-line therapy. It is important to remember that paroxysmal atrial fibrillation is not an arrhythmia that is going to kill patients right away, so there is reasonable time to try drug therapy. With this study we wanted to see if it was better to try other drugs or go straight to ablation."

Presenting the results of the Atrial Fibrillation Ablation versus Antiarrhythmic Drugs (A4) study during the late-breaking clinical-trials session, Jais and colleagues concluded that it is better to move directly to ablation in patients who failed antiarrhythmic drug therapy. These patients, in addition to being free from the arrhythmia, also reported better quality of life.

Data from randomized trials starting to roll in

Early randomized data in support of catheter ablation for the treatment of paroxysmal AF are starting slowly to emerge. At the American Heart Association 2006 Scientific Sessions in Atlanta, GA, Dr Carlo Pappone (San Raffaele University Hospital, Milan, Italy) presented data showing that more ablated patients were in normal sinus rhythm at nine months compared with patients treated with antiarrhythmic drug therapy. These findings mirrored a study by Oral et al in the New England Journal of Medicine showing that sinus rhythm can be maintained long term in a majority of chronic AF patients treated with circumferential pulmonary vein ablation rather than with drug therapy [2].

In the present study, the A4 investigators randomized 112 patients, average age 51 years, who previously failed antiarrhythmic drug therapy to catheter ablation or further drug therapy with a different agent. In total, 53 patients underwent catheter ablation and 59 patients were treated with drug therapy. Overall, 21% of patients had structural heart disease and 80% were on anticoagulants.

There was a three-month blanking period to allow investigators to make up to three attempts at successful treatment in each study arm. After three months, patients who failed treatment in either arm were allowed to cross over to the other treatment group. In the ablation patients, ostial pulmonary vein isolation was confirmed using a Lasso catheter, with additional focal or linear ablation lesion sets added if required. The primary end point of the study was the recurrence of AF and was strictly defined as the recurrence of any episode of AF after the third month lasting more than three minutes.

Of the 53 patients treated with ablation, 75% were free of AF at one year. In addition, 60% of patients had stopped oral anticoagulation therapy. In contrast, just 7% of patients in the antiarrhythmic-drug-therapy arm were free from AF at one year. Moreover, 37 patients crossed over to the catheter-ablation study arm after failing drug therapy in the first three months. Of the 22 patients who did not cross over, just 25% stopped anticoagulation at one year. Quality-of-life scores also improved significantly with catheter ablation, and although the greatest improvement was observed between baseline and three months, improvements were maintained at one year, suggesting a real, rather than placebo, effect, said Jais.

Jais told heartwire that the study also contained a subgroup of 24 patients in the drug-therapy arm who had never taken amiodarone. When these amiodarone-naive patients in the antiarrhythmic study arm were treated with the drug, 79% did not respond to the agent, suggesting that AF control is unlikely in patients who do not respond to a first drug.

"Amiodarone is the most powerful drug that we have for atrial fibrillation—for most arrhythmias, in fact," said Jais. "Yet, in these 24 patients who received amiodarone for the first time, almost 80% failed. The message is really clear in that if you fail one drug it is very unlikely that you are going to be properly controlled with any other drug, including amiodarone. In patients who failed drug therapy, ablation looks much better."

Ablated patients underwent an average of 1.8 procedures, and there were two reported cases of tamponade, one in a patient who crossed over to the ablation arm. There was one case of pulmonary vein stenosis, occurring also in a patient who crossed over to ablation. There was one reported case of hyperthyroidism in a patient undergoing antiarrhythmic drug therapy.

Was the primary end point too strict?

During the question-and-answer session, moderator Dr John Camm (St George's Hospital Medical School, London, UK) asked Jais about the end point, wondering if it were too strict. Camm questioned whether the results of the study would have differed had investigators not classified drug therapy as a failure if AF persisted for longer than three minutes. Most of these patients, he said, are not in a rush to cross over to ablation, and more time would have allowed a greater accumulation of data and a better chance of drug therapy success.

Jais acknowledged that the end point was very strict, adding that it is difficult to select the proper end point in ablation trials. He said that while the primary end point defined failed therapy as an AF episode exceeding three minutes, most patients greatly exceeded this threshold and some were in AF for three to four hours. In his conclusions, Jais stressed that additional studies are needed to assess the longer-term outcomes of both treatment strategies.

The Atrial Fibrillation Ablation versus Antiarrhythmic Drugs study was sponsored by BioSense Webster.