Stop AF First Clinical Trial
STOP AF First is a prospective, multicenter, randomized study designed to evaluate the safety and effectiveness of the Medtronic cryoablation system as an initial first-line rhythm control treatment in patients with symptomatic paroxysmal atrial fibrillation (PAF).
Purpose and design
The STOP AF First Trial1,2 (NCT03118518) is a prospective, multicenter randomized study evaluating whether cryoballoon catheter ablation is superior to antiarrhythmic drug (AAD) therapy as a first-line rhythm control treatment in patients with symptomatic paroxysmal atrial fibrillation (PAF). A total of 225 drug-naïve patients (AAD for < 7 days) with symptomatic PAF aged 18–80 were enrolled at 24 centers in the United States. The Arctic Front Advance™ cryoballoon was used to establish pulmonary vein isolation (PVI) and the drug therapy arm received a class I or III AAD therapy.
Key findings
Primary Safety Endpoint Met 1.9%
Low Complication Rate
Primary safety events occurred in two subjects (estimated 12-month rate: 1.9%, 95% CI: 0.5–7.5%) in the cryoballoon arm. Since the upper bound of the 95% confidence interval was below the prespecified performance goal, the primary safety endpoint was met.
< 2% Serious Complication Rate
Primary Effectiveness Endpoint Met 74.6%
Freedom from Acute Procedural Failure or Atrial Arrhythmia Recurrence 12 Months Post-ablation
By modified intention-to-treat analysis (which included all randomized patients who initiated therapy), freedom from primary efficacy failure was:
- 74.6% in the cryoballoon arm
- 45.0% in the AAD arm (p < 0.001)
Quality-of-life Outcomes
A significant improvement (p < 0.01) in subjects’ quality of life was observed at 12 months for those in the ablation group as assessed with the AFEQT and EQ-5D questionnaires. Improvements in AF-specific quality of life at 12 months assessed using the AFEQT were larger with cryoballoon ablation versus AAD therapy.
Endpoints
Primary efficacy endpoint
Treatment success at 12 months
Treatment failure is defined as:
- Acute procedural failure*
- Any subsequent AF surgery or ablation in the left atrium (including those performed during the blanking period)
- Any of the following after the 90-day blanking period:
- Documented AF/AT/AFL
- Cardioversion
- Class I or III AAD use*
Primary safety endpoint
Composite of prespecified procedure- and system-related serious adverse events evaluated in the cryoballoon catheter ablation arm (prespecified performance goal: failure rate < 12%).
Primary safety events include:
- Within 7 days:
- Transient ischemic attack
- Stroke
- Major bleeding
- Myocardial infarction
- Vascular complication
- Within 30 days:
- Significant pericardial effusion
- Within 12 months:
- Symptomatic pulmonary vein stenosis
- Atrial-esophageal fistula
- Unresolved phrenic nerve injury at 12 months
Patient inclusion criteria
Key inclusion criteria
- A diagnosis of symptomatic PAF with the following documentation:
- Physician’s note indicating recurrent self-terminating AF or PAF; and
- Any ECG-documented AF within 6 months prior to enrollment
- Age 18–80
Key exclusion criteria
- History of AF treatment with class I or III AAD, including sotalol, with the intention to prevent an AF recurrence. However, patients pretreated with above AAD for less than 7 days with the intention to convert an AF episode were allowed.
- Prior left atrial ablation or left atrial surgical procedure
- Prior persistent AF (continuous AF > 7 days)
- Left atrial diameter > 5.0 cm
- NYHA class III or IV congestive heart failure and/or known left ventricular ejection fraction (LVEF) less than 45%
Recurrence monitoring
- Patient-activated Ambulatory ECG (TTM; weekly and when symptomatic)
3 months and beyond - 12-lead ECG
Baseline, 1, 3, 6, and 12 months - 24-hour Continuous Ambulatory ECG
6 and 12 months
*
Treatment arm only.
Reference
1
Wazni OM, Dandamudi G, Sood N, et al. Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation. N Engl J Med. January 28, 2021;384(4):316-324.
2
Wazni OM, Dandamudi G, Sood N, et al. Cryoablation versus antiarrhythmic drug therapy as initial treatment for atrial fibrillation: impact on quality of life. J Am Coll Cardiol. 2021;77(18_Supplement_1):225-225.