STOP-AF and CABANA: Trials Show Effectiveness of Ablation Over Drugs in AF

March 15, 2010

March 15, 2010 (Atlanta, Georgia) — Patients with drug-refractory paroxysmal atrial fibrillation (AF) treated with a novel cryoablation technology (Arctic Front CryoAblation Catheter System, Medtronic) were significantly more likely to be free of arrhythmia at one year compared with antiarrhythmic drug therapy, according to the results of a new study.

Dr Douglas Packer

The researchers, led by Dr Douglas Packer (Mayo Clinic, Rochester, MN), showed that 70% of patients treated with the cryoballoon were free from AF at one year, compared with just 7% of patients who were treated with another antiarrhythmic agent.

"It's a relatively new technology in the hands of the investigators using them," said Packer during a morning press conference announcing the results. "The potential advantage of the balloon approach into a vein is the possibility of completely isolating the vein in one freeze, or a couple of freezes, as opposed to having to move the catheter to different locations."

The results of the study, known as the Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP-AF) trial, were presented today at the American College of Cardiology 2010 Scientific Sessions.

Highly Symptomatic Patient Cohort

The new balloon device works on the same premise as a radiofrequency-ablation device, with the aim of blocking electrical conduction in myocardial tissue. Instead of radiofrequency current, however, the device delivers extreme cold. With this device, the catheter is designed as a balloon, which allows the surface area of the encircling atrial tissue of the pulmonary vein to be ablated at once, and is designed to reduce the number of lesions required.

"In the procedure," said Packer, "the notion is pulmonary vein isolation, so a balloon catheter has to be positioned into the orifice of the vein, but not into the vein. So there is a little bit of trick to that, knowing when you're at the orifice and knowing when you're not at the orifice. . . . It's a technology that has only been around for a short period of time, so all of the fundamental experience with RV ablation catheters, dating back to 1991, has to be replaced by a little bit of a learning curve."

In the STOP-AF trial, investigators enrolled 245 patients with paroxysmal AF at 26 centers with the purpose of comparing the cryoballoon ablation technique with antiarrhythmic drug therapy. Patients enrolled in the study had two or more episodes of AF within two months as documented by electrocardiogram or had failed at least one antiarrhythmic drug. During the clinical-trials session, Packer noted that the patients were relatively young, with little documented heart disease, but did have frequent, highly symptomatic AF, failing, on average, 1.2 antiarrhythmic drugs. Based on their CHADS2 score, however, they were a low-risk cohort of patients, he said.

After a three-month blanking period and nine-month follow-up, 69.9% of patients treated with cryoablation were free from AF--defined as no detectable AF during the nonblanking period, no use of study drugs, and no AF interventions--compared with 7.3% of patients treated with antiarrhythmic drug therapy. Among the successfully ablated patients, 58% were free from AF at one year without the use of add-on antiarrhythmic drug therapy, and 60% were free from AF after a single ablation procedure.

Serious adverse events related to the cryoablation procedure or device occurred in five patients. In a combined safety end point that included adverse events related to treatment and disease, the two approaches, cryoablation and antiarrhythmic drug therapy, were similar. Phrenic nerve paralysis did occur in 29 patients treated with cryoablation, but this resolved at 12 months in 25 individuals. Of the remaining four patients with persisting phrenic nerve paralysis, one had symptoms. Pulmonary vein stenosis occurred in five patients.

Asked by Dr John Miller (Krannert Institute of Cardiology, Indianapolis, IN) during the clinical-trials session about the rates of adverse events, Packer said the solution to the problem is experience. "One of the hallmarks of this study is that it was not exclusively conducted in academic centers in sites where hundreds of procedures have been performed," he said. Procedure times, which were, on average, six hours long, would also be expected to come down with experience, he added.

Despite the success of the novel ablation technology, Packer said the question of whether or not patients should continue taking warfarin following the procedure is based on their risk for thromboembolic events. If they are free from AF and have a low risk, with a CHADS2 score of 0 or 1, then they more than likely can come off warfarin. If they are free from AF but still have an elevated underlying risk of thromboembolic events, these patients should remain on the drug, he said.

The CABANA Trial

In addition to the STOP-AF trial, Packer presented the results from the pilot Catheter Ablation vs Antiarrhythmic Drug Therapy for Atrial Fibrillation (CABANA) study. In contrast to the first study, CABANA included more difficult-to-treat patients, with roughly two-thirds of patients having persistent or long-standing persistent AF. Individuals enrolled in the trial also had more comorbidities, including coronary artery disease, hypertension, and diabetes mellitus.

Although the primary end point of the study was freedom from AF, the study was designed to test the feasibility of a long-awaited clinical trial assessing hard clinical end points, including mortality and stroke, with AF ablation. In the pilot study, 60 patients were enrolled and followed for nine months following a three-month blanking period.

At the completion of the trial, 65% of patients treated with catheter ablation were free from symptomatic AF, compared with 41% treated with antiarrhythmic drugs, a significant 58% reduction in relative risk. In terms of the recurrence of any AF, atrial flutter, or atrial tachycardia, 72% were free from these arrhythmias following ablation, while 66% treated with drug therapy were without the arrhythmias, a nonsignificant difference.

During the morning press conference, Packer noted that the late recurrence of AF might reduce the long-term effectiveness of ablation and said there is some concern that the relative effectiveness of the two therapies could be similar over time. The results of CABANA are less impressive than the STOP-AF trial, but the patients differed significantly, he said.

"There is another critical point, and I think this is the real message of a trial like CABANA: it's not about the recurrence of atrial fibrillation," he said. "It has to be about mortality. It has to be about other aggravating issues like stroke. It has to be about cost, and it has to be about complications. In a way you could say that the recurrence of atrial fibrillation is a surrogate. If these patients have a very good quality of life at low cost to the healthcare system, then we're talking benefit."

The CABANA trial, sponsored by the National Heart, Lung, and Blood Institute, as well as Duke University, St Jude Medical, and Biosense Webster, is now enrolling and will include up to 3000 patients followed for an estimated duration of five years. The primary end point is total mortality, and secondary end points include a host of cardiovascular end points, including hospitalizations, bleeding, and stroke, among others.

During the late-breaking clinical-trials session, Dr John Camm (St George's Hospital Medical School, London, UK) questioned whether CABANA is sufficiently powered to address these hard cardiovascular end points and whether or not the crossovers from drug therapy to ablation or drug therapy added to ablated patients would dilute the findings. Results from the study are not expected for some time.