Table 7.
Selected clinical trials of catheter ablation of atrial fibrillation and/or for FDA approval
| Trial | Year | Type | N | AF type | Ablation strategy | Initial time frame | Effectiveness endpoint | Ablation success | Drug/ Control success | P value for success | Ablation complications | Drug/ Control complications | Comments |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Clinical Trials Performed for FDA Approval | |||||||||||||
| JAMA 2010; 303: 333-340 (ThermoCool AF)14 | 2010 | Randomized to RF ablation or AAD, multicenter | 167 | Paroxysmal | PVI, optional CFAEs and lines | 12 months | Freedom from symptomatic paroxysmal atrial fibrillation, acute procedural failure, or changes in specified drug regimen | 66% | 16% | <0.001 | 4.9% | 8.8% | FDA approval received |
| JACC 2013; 61: 1713-1723 (STOP AF)9 | 2013 | Randomized to cryoballoon ablation or AAD, multicenter | 245 | Paroxysmal | PVI | 12 months | Freedom from any detectable AF, use of nonstudy AAD, or nonprotocol intervention for AF | 70% | 7% | <0.001 | 3.1% | NA | FDA approval received |
| Heart Rhythm 2014; 11: 202-209 (TTOP)22 | 2014 | Randomized to phased RF ablation or AAD/cardioversion, multicenter | 210 | Persistent | PVI + CFAEs | 6 months | Acute procedural success, ≥90% reduction in AF burden, off AAD | 56% | 26% | <0.001 | 12.3% | NA | Not FDA approved |
| JACC 2014; 64: 647-656 (SMART-AF)13 | 2014 | Nonrandomzied multicenter study of contact force-sensing RF catheter, comparing to performance goals | 172 | Paroxysmal | PVI, optional CFAEs and lines | 12 months | Freedom from symptomatic AF, flutter, tachycardia, acute procedural failure, or changes in AAD | 72.5% | N/A | <0.0001 | 7.5% | NA | FDA approval received |
| Circulation 2015; 132: 907-915 (TOCCASTAR)12 | 2015 | Randomized to contact force sensing RF catheter or approved RF catheter, multicenter | 300 | Paroxysaml | PVI, optional triggers, CAFEs and lines in both arms | 12 months | Acute procedural success + Freedom from Symptomatic AF/Flutter/Tachycardia off AAD | 67.8% | 69.4% | 0.0073 for noninferiority | 7.2% | 9.1% | FDA approval received |
| JACC 2015; 66: 1350-1360 (HeartLight)11 | 2015 | Randomized to laserballoon or approved RF catheter, multicenter | 353 | Paroxysmal | PVI ± CTI ablation vs PVI, optional CFAEs, and Lines | 12 months | Freedom from Symptomatic AF/Flutter/Tachycardia, acute procedural failure, AAD, or non-prototocol intervention | 61.1% | 61.7% | 0.003 for noninferiority | 5.3% | 6.4% | FDA approval received |
| First-Line Therapy Trials | |||||||||||||
| JAMA 2005; 293: 2634-2640 (RAAFT)29 | 2005 | Randomized to drug, multicenter | 70 | Paroxysmal (N=67), persistent (N= 3) | PVI | 12 months | Freedom from detectable AF | 84% | 37% | <0.01 | 9% | 11% | |
| NEJM 2012; 367:1587-1595 (MANTRA-PAF)30 | 2012 | Randomized to drug, multicenter | 294 | Paroxysmal AF | PVI, roof line, optional mitral and tricuspid line | 24 months | Cumulative AF burden | 13% AF burden | 19% AF burden | NS | 17% | 15% | |
| JAMA 2014; 311: 692-700 (RAAFT-2)31 | 2014 | Randomized to drug multicenter | 127 | Paroxysmal AF | PVI plus optional non-PVI targets | 24 months | Freedom from detectable AF, flutter, tachycardia | 45% | 28% | 0.02 | 9% | 4.9% | |
| Other Paroxysmal AF Ablation Trials | |||||||||||||
| JACC 2006; 48: 2340-2347 (APAF)16 | 2006 | Randomized to drug single center | 198 | Paroxysmal AF | PVI, mitral line and tricuspid line | 12 months | Freedom from detectable AF, flutter, tachycardia | 86% | 22% | <0.001 | 1% | 23% | |
| Circulation 2008; 118: 2498-2505 (A4)7 | 2008 | Randomized to drug | 112 | Paroxysmal | PVI (optional LA lines, CTI, focal) | 12 months | Freedom from AF | 89% | 23% | <0.0001 | 5.7% | 1.7% | |
| NEJM 2016; 374: 2235-2245 (FIRE AND ICE)10 | 2016 | Randomized RF vs Cryo, multicenter | 762 | Paroxysmal AF | PVI | 12 months | Freedom from detectable AF, flutter, tachycardia | 64.1% (RF) | 65.4% (cryo) | NS | 12.8% | 10.2% | |
| JACC 2016; 68: 2747-275715 | 2016 | Randomized to hot balloon or drug, multicenter | 100 | Paroxysmal AF | PVI | 12 months | Freedom from AF | 59% | 5% | <0.001 | 10.4% | 4.7% | |
| Other Persistent AF Ablation Trials | |||||||||||||
| NEJM 2006; 354: 934-94125 | 2006 | Randomized to RF ablation or to CV and short term amio | 146 | Persistent | PVI, roof, mitral line | 12 months | No AF or flutter month 12 | 74% | 58% | 0.05 | 1.3% | 1.4% | |
| EHJ 2014; 35: 501-507 (SARA)26 | 2014 | Randomized to drug (2:1 ablation to drug), multicenter | 146 | Persistent | PVI (optional LA lines, CFAEs) | 12 months | Freedom from AF/flutter lasting >24h | 70% | 44% | 0.002 | 6.1% | 4.20% | |
| NEJM 2015; 372: 1812-182219 | 2015 | Randomized ablation strategies, multicenter | 589 | Persistent | PVI alone versus PVI & CFAEs or PVI & lines | 18 months | Freedom from afib with or without drugs | 59% (PVI alone) | 49% & 46% | NS | 6% | 4.3% & 7.6% | |
| Other Mixed Paroxysmal and Persistent AF Ablation Trials | |||||||||||||
| J Med Assoc Thai 2003; 86 (Suppl 1): S8-S1624 | 2003 | Randomized to RF ablation or amiodarone | 30 | Paroxysmal (70%), Persistent (30%) | PVI, mitral line, CTI, SVC to IVC | 12 months | Freedom from AF | 79% | 40% | 0.018 | 6.70% | 47% | |
| EHJ 2006; 27: 216-22117 | 2006 | Randomized to RF ablation or drug, multicenter | 137 | Paroxysmal (67%), Persistent (33%) | PVI, mitral line, CTI | 12 months | Freedom from AF, flutter, tachycardia | 66% | 9% | <0.001 | 4.40% | 2.90% | |
| JCVEP 2009, 20: 22-2818 | 2009 | Randomized to RF ablation or drug, multicenter | 70 | Paroxysmal (41%), Persistent (59%) & type 2 DM | PVI, CTI, optional mitral line and roof line | 12 months | Freedom from AF and atypical atrial flutter | 80% | 43% | 0.001 | 2.90% | 17% | |
| Randomized Trials of AF Ablation in Patients with Heart Failure | |||||||||||||
| NEJM 2008; 359: 1778-1785 (PABA-HF)38 | 2008 | Randomized to RF ablation of AVJ abl and BiV pacing | 81 | Persistent (50%), Paroxysmal (50%), EF 27% abl, 29% AVJ | PVI, optional linear abl and CFAEs | 6 months | Composite EF, 6 min walk, MLWHF score; freedom from AF (secondary, mult proc, +/- AA drugs) | 88% AF free, EF 35% abl, 28% AVJ (P <.001), > QOL and 6 min walk increase with abl | <0.001 | 14.60% | 17.50% | ||
| Heart 2011; 97: 740-74739 | 2011 | Randomized to RF ablation or pharmacological rate control | 41 | Persistent, EF 20% abl, 16% rate control | PVI, roof line, CFAEs | 6 months | Change in LVEF, sinus rhythm at 6 months (secondary) | 50% in NSR, LVEF increase 4.5% | 0% in NSR, LVEF increase 2.8% | 0.6 (for EF increase) | 15% | Not reported | |
| JACC 2013; 61: 1894-190346 | 2013 | Randomized to RF ablation or pharmacological rate control | 52 | Persistent AF (100%), EF 22% abl, 25% rate control | PVI, optional linear abl and CFAEs | 12 months | Change in peak O2 consumption (also reported single procedure off drug ablation success) | Peak O2 consumption increase greater with abl, 72% abl success | 0.018 | 15% | Not reported | ||
| Circ A and E 2014; 7: 31-3840 | 2014 | Randomized to RF ablation or pharmacological rate control | 50 | Persistent AF (100%), EF 32% abl, 34% rate control | PVI, optional linear abl and CFAEs | 6 months | Change in LVEF at 6 months, multiple procedure freedom from AF also reported | LVEF 40% with abl, 31% rate control, 81% AF free with abl | 0.015 | 7.70% | |||
AF, atrial fibrillation; RF, radiofrequency; AVJ, atrioventricular junction; abl, ablation; BiV, biventricular; EF, ejection fraction; PVI, pulmonary vein isolation; CFAEs, complex fractionated atrial electrograms; MLWHF, Minnesota Living with Heart Failure; LVEF, left ventricular ejection fraction; QOL, quality of life; NSR, normal sinus rhythm.