Ablation for Paroxysmal Atrial Fibrillation (APAF) Trial Presented at The American College of Cardiology Scientific Session 2006 Presented by Dr. Carlo Pappone APAF Trial

www. Clinical trial results.org APAF Trial: Background AF affects between 2 and 3 million people in the United StatesAF affects between 2 and 3 million people in the United States Antiarrhythmic drugs have limited use in treating AF due to side effects and increased mortalityAntiarrhythmic drugs have limited use in treating AF due to side effects and increased mortality The present trial sought to investigate the treatment of paroxysmal atrial fibrillation using an alternative to pharmacologic treatmentThe present trial sought to investigate the treatment of paroxysmal atrial fibrillation using an alternative to pharmacologic treatment AF affects between 2 and 3 million people in the United StatesAF affects between 2 and 3 million people in the United States Antiarrhythmic drugs have limited use in treating AF due to side effects and increased mortalityAntiarrhythmic drugs have limited use in treating AF due to side effects and increased mortality The present trial sought to investigate the treatment of paroxysmal atrial fibrillation using an alternative to pharmacologic treatmentThe present trial sought to investigate the treatment of paroxysmal atrial fibrillation using an alternative to pharmacologic treatment Presented at ACC 2006

www. Clinical trial results.org APAF Trial: Study Design  Primary Endpoint: Freedom from recurrent atrial arrhythmias  Secondary Endpoint: Monthly rhythm analysis; adverse events, left atrium remodeling  Primary Endpoint: Freedom from recurrent atrial arrhythmias  Secondary Endpoint: Monthly rhythm analysis; adverse events, left atrium remodeling Circumferential pulmonary vein ablation (CPVA) n=99 Circumferential pulmonary vein ablation (CPVA) n=99 Antiarrhythmic medical therapy n=99 with flecainide (n=33) with sotalol (n=33) with amiodarone (n=33) Antiarrhythmic medical therapy n=99 with flecainide (n=33) with sotalol (n=33) with amiodarone (n=33) 198 patients age presenting with paroxysmal atrial fibrillation >6 months and qualifying atrial fibrillation burden >2 episodes per month/ Randomized. 33% female, mean age 56 years, mean follow-up 12 months 198 patients age presenting with paroxysmal atrial fibrillation >6 months and qualifying atrial fibrillation burden >2 episodes per month/ Randomized. 33% female, mean age 56 years, mean follow-up 12 months Presented at ACC 2006 Following a 1-month run-in phase to uptitrate antiarrhythmic medical therapy in both arms, ablation was performed in patients randomized to CPVA to encircle all 4 PVs with 3 additional lines to prevent atrial tachycardias (ATs) using either a 8mm or a 3.5mm irrigated tip catheter and with the guide of CARTO or NavX system. Medical therapy was discontinued in the CPVA group. Crossovers were allowed after 3 months.

www. Clinical trial results.org APAF Trial: Baseline data from 150 patients Presented at ACC 2006 number of AF episodes per year number of AF episodes per year Atrial Fibrillation Episodes per Year at Time of Enrollment p=0.05 Paroxysmal atrial fibrillation duration averaged 6 years at the time of enrollmentParoxysmal atrial fibrillation duration averaged 6 years at the time of enrollment AF episodes per year were more common in the CPVA group at baseline (52 vs 30; p=0.05)AF episodes per year were more common in the CPVA group at baseline (52 vs 30; p=0.05) Baseline ejection fraction was 60%Baseline ejection fraction was 60% History of hypertension was found in 56% of patientsHistory of hypertension was found in 56% of patients

www. Clinical trial results.org APAF Trial: Primary Endpoint at 9 months Presented at ACC 2006 Freedom from recurrent AF and AT at 9 months (%) p<0.001 At 9 months, a greater number of patients in the CPVA group were free from recurrent AF and AT (all CPVA patients in the absence of antiarrhythmic drug therapy) (87% vs 29%; p<0.001)At 9 months, a greater number of patients in the CPVA group were free from recurrent AF and AT (all CPVA patients in the absence of antiarrhythmic drug therapy) (87% vs 29%; p<0.001)

www. Clinical trial results.org APAF Trial: Recurrent AF Presented at ACC 2006 Of the 8 patients who had recurrent AF in the CPVA group, repeat ablation procedure was performed in 3 patients, one of whom still had additional recurrent AF.Of the 8 patients who had recurrent AF in the CPVA group, repeat ablation procedure was performed in 3 patients, one of whom still had additional recurrent AF. Of the 52 patients who had recurrent AF in the control group, 38 had CPVA performed, 4 of whom still had additional recurrent atrial fibrillationOf the 52 patients who had recurrent AF in the control group, 38 had CPVA performed, 4 of whom still had additional recurrent atrial fibrillation

www. Clinical trial results.org APAF Trial: Secondary Endpoints Presented at ACC 2006 At 12 months, there was a significant decrease in left atrium diameter in patients randomized to CPVA (p<0.05), but no difference in patients randomized to the control groupAt 12 months, there was a significant decrease in left atrium diameter in patients randomized to CPVA (p<0.05), but no difference in patients randomized to the control group Adverse events in the CPVA group included 1 TIA and 1 pericardial effusionAdverse events in the CPVA group included 1 TIA and 1 pericardial effusion

www. Clinical trial results.org TAXUS V ISR Trial: Limitations This trial excluded many AF patients on the basis of age and disease progression: patients older than 70 and those with an enlarged atrium or low ejection fraction (<35%) were excluded from the APAF Trial. Future trials might look to include these patients who better represent the real-world AF population.This trial excluded many AF patients on the basis of age and disease progression: patients older than 70 and those with an enlarged atrium or low ejection fraction (<35%) were excluded from the APAF Trial. Future trials might look to include these patients who better represent the real-world AF population. The current trial is too short to adequately assess and answer important safety concerns.The current trial is too short to adequately assess and answer important safety concerns. This trial excluded many AF patients on the basis of age and disease progression: patients older than 70 and those with an enlarged atrium or low ejection fraction (<35%) were excluded from the APAF Trial. Future trials might look to include these patients who better represent the real-world AF population.This trial excluded many AF patients on the basis of age and disease progression: patients older than 70 and those with an enlarged atrium or low ejection fraction (<35%) were excluded from the APAF Trial. Future trials might look to include these patients who better represent the real-world AF population. The current trial is too short to adequately assess and answer important safety concerns.The current trial is too short to adequately assess and answer important safety concerns. Presented at ACC 2006

www. Clinical trial results.org TAXUS V ISR Trial: Summary Among patients with paroxysmal atrial fibrillation, treatment with circumferential pulmonary vein ablation was associated with a reduction in recurrent AF and AT compared with conventional antiarrhythmic medical therapy at 12 monthsAmong patients with paroxysmal atrial fibrillation, treatment with circumferential pulmonary vein ablation was associated with a reduction in recurrent AF and AT compared with conventional antiarrhythmic medical therapy at 12 months Medical management of AF can be difficult as it requires frequent monitoring. CPVA has been used as an alternative management strategy for AF but randomized data comparing the two therapies are limited.Medical management of AF can be difficult as it requires frequent monitoring. CPVA has been used as an alternative management strategy for AF but randomized data comparing the two therapies are limited. The present trial is one of the first randomized trials of CPVA in the setting of paroxysmal AF. CPVA was recently shown to be beneficial in maintaining sinus rhythm in the setting of chronic AF.The present trial is one of the first randomized trials of CPVA in the setting of paroxysmal AF. CPVA was recently shown to be beneficial in maintaining sinus rhythm in the setting of chronic AF. Full one-year data for the entire cohort of this trial are not yet available, although the 9-month data are very positive.Full one-year data for the entire cohort of this trial are not yet available, although the 9-month data are very positive. Among patients with paroxysmal atrial fibrillation, treatment with circumferential pulmonary vein ablation was associated with a reduction in recurrent AF and AT compared with conventional antiarrhythmic medical therapy at 12 monthsAmong patients with paroxysmal atrial fibrillation, treatment with circumferential pulmonary vein ablation was associated with a reduction in recurrent AF and AT compared with conventional antiarrhythmic medical therapy at 12 months Medical management of AF can be difficult as it requires frequent monitoring. CPVA has been used as an alternative management strategy for AF but randomized data comparing the two therapies are limited.Medical management of AF can be difficult as it requires frequent monitoring. CPVA has been used as an alternative management strategy for AF but randomized data comparing the two therapies are limited. The present trial is one of the first randomized trials of CPVA in the setting of paroxysmal AF. CPVA was recently shown to be beneficial in maintaining sinus rhythm in the setting of chronic AF.The present trial is one of the first randomized trials of CPVA in the setting of paroxysmal AF. CPVA was recently shown to be beneficial in maintaining sinus rhythm in the setting of chronic AF. Full one-year data for the entire cohort of this trial are not yet available, although the 9-month data are very positive.Full one-year data for the entire cohort of this trial are not yet available, although the 9-month data are very positive. Presented at ACC 2006