Table 2. Randomized clinical trials of catheter ablation for atrial fibrillation.

Study	Design	Patient population	N	Intervention	Comparator	Endpoints	Follow-up (mean ± SD)	Outcomes
First-line therapy
RAAFT-1 Wazni et al52	RCT Multicenter	Symptomatic PAF (96%) and persistent AF Pooled mean age 53 ± 8 years % male not reported	70	PVI	AAD	Primary: Recurrent AF Secondary: Hospitalization, quality of life	12 months	87% PVI vs 37% AAD group freedom from AF recurrence 9% PVI vs 54% AAD hospitalization Greater improvement in quality of life with PVI
MANTRA-PAF Cosedis Nielson et al53	RCT Multicenter	Symptomatic PAF Pooled mean age 55 ± 10 years 70% male	294	PVI + additional ablation at operator's discretion	AAD	Primary: Burden of AF Secondary: Freedom from AF, symptoms, time to first recurrence, quality of life	24 months	No significant difference in cumulative burden of AF 9% PVI vs 18% AAD AF burden at 24 months 85% PVI vs 71% AAD freedom from any AF recurrence Quality of life improved equally in both groups
RAAFT-2 Morillo et al54	RCT Multicenter	Symptomatic PAF Pooled mean age 55 ± 10 years 76% male	127	PVI + additional ablation at operator's discretion	AAD	Primary: Recurrent AF Secondary: Symptomatic AF, quality of life	24 months	45% PVI vs 28% AAD freedom from AF recurrence 53% PVI vs 41% AAD freedom from recurrent symptomatic AF Quality of life improved equally in both groups
Second-line therapy
A4 Study Jais et al55	RCT Multicenter Superiority	Symptomatic drug-refractory PAF Pooled mean age 51 ± 11 years 84% male	108	PVI + additional ablation at operator's discretion	AAD	Primary: Recurrent AF at 3-12 months, freedom from AF after ≤3 procedures, changes in AAD within 3 months Secondary: Time to recurrent AF, quality of life, exercise capacity, AF burden	12 months	Greater freedom from AF in the ablation (89%) vs AAD (23%) group More favorable symptom scores, exercise capacity, and quality of life in ablation group
APAF study Pappone et al56	RCT Single-center	Symptomatic drug-refractory PAF Pooled mean age 56 ± 10 years 67% male	198	PVI + additional ablation at operator's discretion	AAD	Primary: Freedom from AF at 12 months	12 months	Greater freedom from AF in the ablation vs AAD group (93% vs 35% at 1 year) Fewer cardiovascular hospitalizations in ablation group
Wilber et al57	RCT Multicenter	Symptomatic drug-refractory PAF Pooled mean age 56 years (95% CI 54.1–57.4) 67% male	167	PVI + additional ablation at operator's discretion	AAD	Primary: Freedom from symptomatic AF, safety Secondary: Freedom from any atrial arrhythmia, quality of life	PVI group: median 12.5 (95% CI 11.9–13.1) months AAD group: median 14.3 (95% CI 9.4–15.5) months	Greater freedom from AF in the ablation vs AAD group (66% vs 16% at 9 months). Greater freedom from any atrial arrhythmia in the ablation vs AAD group (70% vs 19% at 9 months) More favorable quality of life scores in the ablation vs AAD group

AAD = antiarrhythmic drug therapy; CI = confidence interval; PVI = pulmonary vein isolation. Other abbreviations as in Table 1.