Dr Carlo Pappone

Atlanta, GA - Early randomized data in what is likely to be an ongoing story indicate that catheter ablation is superior to drug therapy for the treatment of paroxysmal atrial fibrillation (AF). In a randomized trial of ablation vs conventional antiarrhythmic medications, investigators showed that significantly more patients treated with catheter ablation were in normal sinus rhythm at nine months than were patients treated with antiarrhythmic drug therapy.

"Until a few years ago, the only option and most important strategy for the treatment of this disease was pharmacologic treatment," said lead investigator Dr Carlo Pappone (San Raffaele University Hospital, Milan, Italy) during a media briefing at the American College of Cardiology 2006 Scientific Sessions. "But antiarrhythmic drugs have an intrinsic limitation because of side effects and because of the increase in mortality associated with their use."

The results of the Ablation for Paroxysmal Atrial Fibrillation (APAF) trial, presented today during the late-breaking clinical-trials session, showed that almost 90% of catheter-ablation patients were in normal sinus rhythm at nine months, suggesting that "it is possible to cure atrial fibrillation," said Pappone.

Burden of AF increasing

AF affects between two and three million people in the US alone, and the prevalence is increasing, said Pappone. The most common of the cardiac arrhythmias, it was initially thought to be little more than a nuisance; it is now known to significantly increase the risk of stroke, cardiovascular death, and overall mortality and also affects quality of life. Treatment with antiarrhythmic drugs and anticoagulation is considered front-line therapy in patients with symptomatic AF, despite the fact that these therapies can be suboptimal, said Pappone.

In APAF, investigators randomized 199 patients with paroxysmal AF to one of three drug treatment options—amiodarone, flecainide, or sotalol—or to circumferential pulmonary-vein ablation. In the ablation procedure, operators created encircling lesions around the pulmonary veins, disconnecting them at their junction with the left atrium. They also created three linear lesions, two at the posterior wall of the left atrium and one at the mitral valve that separates the left atrium from the left ventricle.

Patients enrolled were experiencing, on average, three episodes of AF per month and were previously shown to be unable to control their AF with medication. To fully capture the recurrence of AF, including asymptomatic episodes, daily transtelephonic monitoring allowed patients to transmit ECG recordings for one year, with investigators capturing data on 95% of days in follow-up. As part of the study protocol, there was a one-month run-in phase, where all patients were treated with antiarrhythmic drug therapy.

At the time of the presentation, complete data on 150 patients was available. Investigators report that 87% of patients treated with ablation were free of AF at nine months compared with 29% of patients treated with antiarrhythmic drug therapy. Investigators also report that the procedure was safely performed; no serious adverse events were reported, including pulmonary-vein stenosis.

APAF: Freedom from recurrent atrial fibrillation at nine months

End point	Circumferential pulmonary-vein isolation (n=75)	Antiarrhythmic drug therapy (n=75)	p
Freedom from recurrent arrhythmia (%)	87	29	<0.001

All patients in the study were treated with anticoagulation therapy, but anticoagulation was discontinued if there was documented persistence of sinus rhythm, documented positive left-atrial remodeling, or an improvement in delayed transport function. Of the 75 patients treated with ablation, 65 were in normal sinus rhythm at nine months. During a one-month blanking period before follow-up, all 65 had stopped antiarrhythmic drug therapy and all but one had stopped anticoagulation therapy. AF returned in eight patients; five were treated and controlled with antiarrhythmic drug therapy and three underwent an ablative touch-up.

"Reproducibility remains the weak point of the procedure," Pappone told heartwire. "The volume sufficient to achieve the same success rate is about 300 cases per year, and not all centers are able to achieve that. With the incidence of atrial fibrillation increasing, I think the future is in robotic navigation, because it will permit a larger number of clinicians to reproduce results that major centers are producing now."

Weighing in on the data: Long-term study still needed

During the late-breaking clinical-trials sessions, moderator Dr Paul Armstrong (University of Alberta, Edmonton) questioned how generalizable the findings are to clinical practice, hinting that the exclusion criteria of APAF might rule out many patients clinicians see in practice. Many real-world patients with AF are older or have advanced heart failure, but patients older than 70 years and those with an enlarged atrium or low ejection fraction (<35%) were excluded from the APAF trial.

Dr Jim Stein (University of Wisconsin Medical School, Madison) told heartwire that the results of the APAF trial mirror the findings from the recently published study by Oral et al in the New England Journal of Medicine [1]. That study evaluated the potential of circumferential pulmonary-vein ablation for the treatment of chronic AF and showed that sinus rhythm can be maintained long term in a majority of patients treated with ablation.

"I think what this tells us is that for people with atrial fibrillation, pulmonary-vein ablation really does offer them a better chance of staying in sinus rhythm," said Stein. "The key question, as a clinician, still remains: Can we stop their warfarin? The biggest complaint that people with atrial fibrillation have is that they have to take warfarin, with its attendant monitoring and bleeding risk."

Stein said that although patients were able to stop anticoagulation, the nine-month follow-up of patients in this trial still does not answer important safety questions. "It's too short a study for anything other than safety of procedure," said Stein. "It's not nearly long enough to tell us whether it is safe to stop anticoagulation, and that there won't be late complications from that. In all the antiarrhythmic drug trials, stopping anticoagulation led to an increased stroke rate, but it didn't appear as early as nine months."

The APAF investigators also presented secondary analyses, reporting that the CARTO (Biosense Webster Inc, Diamond Bar, CA) and NavX 3D (St Jude Medical, St Paul, MN) mapping systems were both reliable in guiding the ablation procedure. In terms of drug therapy, they report that amiodarone was more effective than sotalol and flecainide in preventing the recurrence of atrial arrhythmias.