ThermoCool AF - ThermoCool AF

Jan 27, 2010
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Trial Sponsor:
Biosense Webster (makers of the NaviStar ThermoCool Irrigated Tip Catheter)
Date Published:
01/01/2010
Date Updated:
01/27/2010
Original Posted Date:
01/27/2010
References

Description:

Numerous small studies have demonstrated the utility of catheter ablation with pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF), as compared with antiarrhythmic drug therapy (ADT). ThermoCool AF is the largest trial to study this question in patients with symptomatic paroxysmal AF, who had not improved with at least one drug.

Hypothesis:

Catheter ablation would be superior to ADT in patients with symptomatic AF.

Study Design

Study Design:

Patients Screened: 5,545
Patients Enrolled: 167
NYHA Class: I (87%), II (13%)
Mean Follow Up: 9 months (with a 3-month blanking period)
Mean Patient Age: 55.7 years
Female: 34
Mean Ejection Fraction: 62.5%

Patient Populations:

  • At least three symptomatic AF episodes within 6 months prior to randomization (≥1 episode verified by electrocardiography)
  • Lack of response to at least one AAD (class I, class III, or atrioventricular nodal blocker)

Exclusions:

  • AF >30 days in duration
  • Age <18>
  • Ejection fraction
  • Previous catheter ablation for AF
  • Documented left atrial thrombus
  • Amiodarone therapy in the preceding 6 months
  • New York Heart Association class III or IV symptoms
  • Myocardial infarction within past 2 months, or coronary artery bypass grafting within past 6 months
  • Thromboembolic event within the past 12 months
  • Severe pulmonary disease
  • Prior valvular cardiac surgical procedure
  • Presence of implantable cardioverter defibrillator
  • Contraindication to ADT or anticoagulation
  • Life expectancy <12>
  • Left atrial size >5 cm in parasternal view

Primary Endpoints:

  • Freedom from protocol-defined treatment failure, which included documented symptomatic paroxysmal AF during the effectiveness evaluation period

Secondary Endpoints:

  • Major treatment-related adverse events at 30 days

Drug/Procedures Used:

Patients were randomized in a 2:1 fashion to either catheter ablation, or a previously unused antiarrhythmic drug (AAD) (Vaughn class I or III). In the catheter ablation group, PVI was performed using the NaviStar ThermoCool Irrigated Tip Catheter, and the Carto Navigation system. Additional ablation was left to the discretion of the investigator. In the ADT arm, a previously unused Food and Drug Administration approved medication for treating AF (dofetilide, flecainide, propafenone, sotalol, quinidine) at dosages recommended by the American College of Cardiology/American Heart Association/European Society of Cardiology was used. The choice of the drug was at the discretion of the investigator.

Concomitant Medications:

Warfarin for 3 months

Principal Findings:

A total of 167 patients were randomized, 106 to catheter ablation, and 61 to ADT. The trial was stopped after the first 150 patients were randomized, when interim analysis suggested a strong benefit with catheter ablation. Baseline characteristics were fairly similar between the two groups. The median duration of AF was about 5.7 years. Structural heart disease was present in about 11%, hypertension was present in about 49%, and cerebrovascular accident/transient ischemic attack was noted in 3% of the patients. The mean atrial diameter was about 4.2 cm. The majority of prior AAD failures were due to propafenone (50.3%). Others included sotalol (35.2%), flecainide (27.9%), amiodarone (7.9%), and dofetilide (2.4%). The mean number of class I/III drugs at baseline was 1.3. Most patients in the ADT arm received either flecainide (36%) or propafenone (41%).

Protocol-defined treatment failure was significantly lower in the catheter ablation arm compared with the ADT arm (16% vs. 66%, hazard ratio 0.30, 95% confidence interval 0.19-0.47, p

The rate of major treatment-related adverse events at 30 days was similar between the catheter ablation and ADT arms (4.9% vs. 8.8, p = NS), including one pericardial effusion in the catheter ablation arm, and two life-threatening arrhythmias in the ADT arm.

Interpretation:

The results of this multicenter trial indicate that catheter ablation with PVI is associated with significantly less treatment failure at 9 months, as compared with ADT, in patients with symptomatic AF, who have failed at least one AAD. There is also a significant reduction in recurrent atrial arrhythmias, a significant improvement in quality of life, without a significant difference in major treatment-related adverse events at 30 days. One limitation of this trial is that even though more than 5,000 patients were screened, only 167 were enrolled. This raises issues with generalizability of these findings. Additionally, all investigators in this trial had extensive experience with catheter ablation, which is a technically challenging procedure. Moreover, ablation practices are not standardized, and a variety of additional ablations besides PVI were frequently employed even in this trial. Hence, outcomes at less experienced centers are likely to be less impressive. Details of rate control between the two groups are also unavailable. Long-term outcomes and cost-effectiveness analyses are also necessary. However, this trial provides supportive evidence regarding the use of catheter ablation for symptomatic AF in patients who have failed at least one AAD.

References:

Wilber DJ, Pappone C, Neuzil P, et al. Comparison of antiarrhythmic drug therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA 2010;303:333-40.

Keywords: Treatment Failure, Stroke, Ischemic Attack, Transient, Quinidine, Potassium Channel Blockers, Pulmonary Veins, Phenethylamines, Electrocardiography, Quality of Life, Research Personnel, Propafenone, Confidence Intervals, Sotalol, Flecainide, Catheter Ablation, Hypertension, Pericardial Effusion, Sulfonamides


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