A-4 Trial Presented at The Heart Rhythm Society Meeting May 2006 Presented by Dr. Pierre Jais Atrial Fibrillation Ablation vs. Antiarrhythmic Drugs Trial

A-4 Trial: Background The goal of this trial was to evaluate catheter ablation compared with antiarrhythmic drug therapy among patients with atrial fibrillation (AF).The goal of this trial was to evaluate catheter ablation compared with antiarrhythmic drug therapy among patients with atrial fibrillation (AF). Presented at HRS 2006

A-4 Trial: Study Design Presented at HRS 2006  Primary Endpoint: Absence of AF for ≥ 3 minutes, either symptomatic or documented  Secondary Endpoint: Quality of life, AF burden, number of AF episodes on Holter, withdrawal of anticoagulant at 1 year  Primary Endpoint: Absence of AF for ≥ 3 minutes, either symptomatic or documented  Secondary Endpoint: Quality of life, AF burden, number of AF episodes on Holter, withdrawal of anticoagulant at 1 year Catheter Ablation n=53 Catheter Ablation n=53 Antiarrhythmic drug therapy with one of 6 medications n=59 Antiarrhythmic drug therapy with one of 6 medications n= patient with symptomatic AF > 6 months, ≥ 2 episodes of AF per month, documentation ≥1 episode of AF, resistant to ≥1 antiarrhythmic drugs from class l or lll Randomized. 16% female, mean age 51 years, mean follow-up 1 year 112 patient with symptomatic AF > 6 months, ≥ 2 episodes of AF per month, documentation ≥1 episode of AF, resistant to ≥1 antiarrhythmic drugs from class l or lll Randomized. 16% female, mean age 51 years, mean follow-up 1 year After the primary endpoint was assessed at 3 months, patients could crossover from medical therapy to ablation, and would be counted as having met the endpoint.

A-4 Trial : Principal Findings At baseline, the average number of AF episodes per month was 20, lasting 9 hours.At baseline, the average number of AF episodes per month was 20, lasting 9 hours. Structural heart disease was present in 21% of patients.Structural heart disease was present in 21% of patients. In the ablation group, the mean procedure duration was 168 minutes, and an average of 1.8 procedures were performed.In the ablation group, the mean procedure duration was 168 minutes, and an average of 1.8 procedures were performed. In the medical therapy group, amiodarone was first used in 24 patients, 80% of whom failed therapy.In the medical therapy group, amiodarone was first used in 24 patients, 80% of whom failed therapy. After month 3, 70% of patients crossed over to ablation therapy.After month 3, 70% of patients crossed over to ablation therapy. Presented at HRS 2006

A-4 Trial: Primary Endpoint Presented at HRS 2006 At one year, 75% of patients in the ablation group and 7% in the medical therapy group were free of arrhythmic recurrence (p<0.05)At one year, 75% of patients in the ablation group and 7% in the medical therapy group were free of arrhythmic recurrence (p<0.05) Patients Free of Arrhythmic Recurrence at 1 Year p<0.05

A-4 Trial: Secondary Endpoint Presented at HRS 2006 Oral anticoagulation therapy was interrupted in 60% of the ablation group and 25% of the medical therapy group.Oral anticoagulation therapy was interrupted in 60% of the ablation group and 25% of the medical therapy group. Among the quality of life parameters 6 of 8 were significantly improved in the ablation group.Among the quality of life parameters 6 of 8 were significantly improved in the ablation group. Among all patients treated with ablation in the trial (n=90 patients and 155 procedures), including crossovers, there were 2 cases of tamponade.Among all patients treated with ablation in the trial (n=90 patients and 155 procedures), including crossovers, there were 2 cases of tamponade. Interruption of Oral Anticoagulation Therapy

A-4 Trial: Limitations One limitation of the trial was the short duration of AF needed to meet the primary endpoint, which was only 3 minutes.One limitation of the trial was the short duration of AF needed to meet the primary endpoint, which was only 3 minutes. Presented at HRS 2006

A-4 Trial: Summary Among patients with atrial fibrillation, catheter ablation was associated with higher rates of absence of AF compared with antiarrhythmic drug therapy.Among patients with atrial fibrillation, catheter ablation was associated with higher rates of absence of AF compared with antiarrhythmic drug therapy. Additionally, it should be noted that patients in the trial had all previously failed antiarrhythmic drug therapy, and results may not be applicable to other AF patients who had not failed therapy or patients who are not symptomatic.Additionally, it should be noted that patients in the trial had all previously failed antiarrhythmic drug therapy, and results may not be applicable to other AF patients who had not failed therapy or patients who are not symptomatic. Among patients with atrial fibrillation, catheter ablation was associated with higher rates of absence of AF compared with antiarrhythmic drug therapy.Among patients with atrial fibrillation, catheter ablation was associated with higher rates of absence of AF compared with antiarrhythmic drug therapy. Additionally, it should be noted that patients in the trial had all previously failed antiarrhythmic drug therapy, and results may not be applicable to other AF patients who had not failed therapy or patients who are not symptomatic.Additionally, it should be noted that patients in the trial had all previously failed antiarrhythmic drug therapy, and results may not be applicable to other AF patients who had not failed therapy or patients who are not symptomatic. Presented at HRS 2006