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Ablation vs. Drugs for Paroxysmal Atrial Fibrillation
Abstract & Commentary
By John P. DiMarco, MD, PhD, Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville. Dr. DiMarco is a consultant for Novartis, and does research for Medtronic and Guidant.
Source: Wilber DJ, et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation. A randomized controlled trial. JAMA. 2010;303:333-340.
Catheter ablation for atrial fibrillation (AF) was first proposed over fifteen years ago but, until recently, there have been no FDA-approved devices specifically labeled for the treatment of AF. In this paper, Wilber and an international consortium of experienced ablation centers, report data from the ThermoCool AF Trial. In this trial, the efficacy of catheter ablation with a NaviStar ThermoCool Irrigated Tip Catheter with guidance using the Carto Navigation System (both made by BioSense Webster) was used for catheter ablation of atrial fibrillation. Patients were eligible for enrollment if they had at least three symptomatic atrial fibrillation episodes within the six months before randomization and had not responded to at least one antiarrhythmic drug (class I, class III, or an AV nodal blocker). Patients were excluded if they had episodes of atrial fibrillation that lasted more than 30 days, an ejection fraction of less than 40%, a moderately enlarged left atrium, prior ablation for atrial fibrillation, New York Heart Association class III or IV heart failure symptoms, or amiodarone therapy within six months. Enrolled patients were randomly assigned in a 2:1 ratio to either ablation or therapy with a previously unused antiarrhythmic drug. The patients were allowed a three-month blanking period after the initial procedure for healing and stabilization before the efficacy assessment period began. Patients assigned to antiarrhythmic drugs had a 14-day dose-titration period before the start of efficacy assessment. Transtelephonic monitoring was performed during a nine-month evaluation period in both groups. Routine weekly transmissions were made during the first eight weeks, and then made monthly until the final visit. All symptomatic episodes were also to be transmitted. Holter monitoring was conducted both at baseline and at the final visit. Antiarrhythmic drugs allowed in the study included flecainide, propafenone, sotalol, quinidine, or dofetilide. The choice of drug was at the discretion of the investigator. Patients in the antiarrhythmic drug therapy group who had either recurrent atrial fibrillation or intolerable side effects could cross over and undergo an ablation procedure after ninety days of therapy.
The endpoint for acute success during the catheter ablation was confirmation of entrance block into all pulmonary veins. The primary endpoint for the study was freedom from treatment failure, defined as documented, symptomatic, paroxysmal AF during the efficacy evaluation period.
Over a three-year period, 167 patients were enrolled in the study, but five patients randomized to antiarrhythmic drug therapy and three patients in the catheter ablation group never received the assigned therapy. For the entire group, the mean age was 55.7 years and 33.5% of the group were women. AF had been present for a mean of 5.7 years, and patients had unsuccessful trials of 1.3 antiarrhythmic drugs before enrollment. There were no significant differences in baseline characteristics between the groups.
Most patients in the antiarrhythmic drug therapy group received either flecainide (36%) or propafenone (41%). Only 11 patients received sotalol; two patients received dofetilide. At the initial procedure, pulmonary isolation was achieved in all patients. A repeat ablation procedure was performed in 13 patients within eighty days of the initial catheter ablation procedure.
Catheter ablation was superior to antiarrhythmic drug therapy in this study. At the end of the nine-month evaluation period, 66% of the patients in the catheter ablation group remained free from treatment failure, compared to 16% of those treated with antiarrhythmic drugs. Five of the 67 patients classified as ablation successes were being treated with previously ineffective antiarrhythmic drugs. In the antiarrhythmic drug therapy group, 36 of 47 patients who had protocol-defined treatment failure crossed over and underwent catheter ablation. Serious treatment-related adverse events were observed in five ablation patients (one pericardial effusion, one episode of pulmonary edema, one pneumonia, one vascular complication, and one progressive heart failure), as well as five patients in the antiarrhythmic drug therapy group (two life-threatening arrhythmias and three disabling drug intolerances). One patient in the catheter-ablation group died suddenly 284 days after the procedure due to a presumed acute myocardial infarction. At the three-month point of the efficacy evaluation, quality-of-life measures were higher in the catheter ablation group compared to the patients treated with antiarrhythmic drug therapy.
The authors concluded that use of the ThermoCool catheter guided by Carto electroanatomical mapping for the treatment of patients with paroxysmal atrial fibrillation was associated with an early and sustained reduction in symptom frequency and severity with a favorable safety profile.
It has been difficult to design trials to demonstrate the effectiveness of ablation tools in patients with atrial fibrillation. The ThermoCool AF Trial results presented in this paper illustrate how far we have come and how far we still have to go in assessing the role of catheter ablation of atrial fibrillation.
It is important to note that, in this trial, the authors selected a very stringent criterion for success. Any symptomatic or asymptomatic atrial arrhythmia detected after the blanking or the drug dose-titration period was considered a treatment failure. Using this strict criterion for success, it is clear that catheter ablation is more effective than antiarrhythmic drug therapy. Drugs rarely, if ever, eliminate all AF episodes in patients with frequent symptoms. Based on these data, one could argue that catheter ablation should be the initial therapy of choice in patients with no or minimal heart disease and paroxysmal atrial fibrillation.
There are a number of features about this report, however, which must be considered before we conclude that catheter ablation is the preferred therapy for the majority of patients with atrial fibrillation. Patients in this trial would, in general, be considered excellent candidates for catheter ablation. They were relatively young, with a mean age of only 55. Although hypertension was present in about half the group, other structural heart disease was uncommon. The left atria were relatively normal in size, and the patients had had paroxysmal atrial fibrillation without progression to persistent atrial fibrillation over a number of years. Catheter-ablation success rates in patients with persistent or chronically persistent atrial fibrillation (greater than one year duration) have lower success rates in almost all studies. These characteristics have been shown in other studies to correlate with excellent results from catheter ablation, but applying these data to the more typical AF patient who may be older, have persistent episodes, and have more structural cardiac disease may not be appropriate.
It was also noted in the presentation of the ThermoCool AF data at the FDA Advisory Committee meeting that there was a significant difference in the success rates between sites in the trial. One large center enrolled 49 patients and reported a 100% success rate with catheter ablation. The other 18 centers enrolled the remaining two-thirds of patients and had a reported success rate of only 47% with catheter ablation. The reasons for this are uncertain, but the highly successful center is a very experienced center, was more aggressive in its use of linear ablation in the cava tricuspid isthmus and in the left atrium, and performed repeat procedures more than the other centers in this trial. It should also be noted that amiodarone and dronedarone were not used in this trial. Since patients had already failed one antiarrhythmic drug, the addition of these other drugs with different mechanisms of action might have improved the results in the drug therapy group.
The clinical endpoints for treating atrial fibrillation patients are mortality, stroke, and symptoms. Only symptoms were evaluated in this trial. The ThermoCool AF trial shows that, in selected patients, catheter ablation by experienced operators may be the best approach to clinical success.