Flecainide versus amiodarone for cardioversion of recent paroxysmal atrial fibrillation in patients with treated coronary artery disease

Safety and Efficacy of Flecainide Versus Amiodarone in the Cardioversion of Paroxysmal Atrial Fibrillation at the Emergency Department, in Patients With Coronary Artery Disease Without Residual Ischemia and Ejection Fraction > 35%

This study will test whether intravenous flecainide works faster and is as safe as intravenous amiodarone to restore normal rhythm in adults with recent paroxysmal atrial fibrillation who have coronary artery disease without ongoing ischemia.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 85 Years
• Sex: All
• Sponsor: Hippocration General Hospital (Academic / other)
• Locations: 3 sites (Athens and 2 other locations)
• Trial ID: NCT05549752 on ClinicalTrials.gov

What this trial studies

This is a prospective, multicenter, randomized Phase 3 trial comparing IV flecainide to IV amiodarone for cardioversion of paroxysmal atrial fibrillation in the emergency department. Eligible patients are adults with recent-onset AF and a history of coronary artery disease without residual ischemia and left ventricular ejection fraction >35%. The trial aims to demonstrate superiority of flecainide for successful cardioversion (including time to cardioversion) while showing non-inferior safety compared with amiodarone. Participants are randomized to receive the assigned antiarrhythmic and monitored in the ED with standard cardiac and hemodynamic surveillance.

Who should consider this trial

Good fit: Adults aged 18–85 presenting to the ED with paroxysmal AF (onset <48 hours, or 48 hours–7 days if anticoagulated ≥30 days) who have prior coronary artery disease without residual ischemia and an ejection fraction >35% are the intended participants.

Not a fit: Patients with ongoing myocardial ischemia, recent myocardial infarction, severely reduced ejection fraction (≤35%), persistent or permanent AF, or other contraindications to class 1C agents or amiodarone are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the study could provide a faster option to restore normal rhythm in this patient group and shorten emergency department stays while expanding safe medication choices.

How similar studies have performed: Flecainide is already known to be effective for cardioversion in patients without structural heart disease, but safety data in patients with prior coronary disease are limited and controversial due largely to older CAST findings, so testing this specific population is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Age: 18-85 years old
2. Paroxysmal Atrial Fibrillation, documented by 12-lead ECG, with one of the following:

   1. Atrial Fibrillation onset less than 48 hours from the time of presentation to the Emergency Department
   2. Atrial Fibrillation onset between 48 hours and 7 days from the time of presentation to the Emergency Department, and patient has been on anticoagulation for at least 30 days
   3. History of Coronary Artery Disease without residual ischemia, defined by one of the following criteria:

      * PCI \<= 1 year, or
      * CABG \<= 3 years, or
      * Negative imaging-based stress testing within 1 year, and:

        * History of known coronary artery stenosis \> 60% without revascularization, or
        * PCI \>= 1 year, or
        * CABG \>= 3 years
3. Ejection Fraction \> 35% (documented by cardiac ultrasound at the Emergency Department, or within 1 year)
4. Signed informed consent from the patient or legal representative.

Exclusion Criteria:

1. Based on ECG at the Emergency Department:

   1. Atrial Flutter
   2. Newly documented Left Bundle Branch Block (LBBB)
   3. Newly documented Right Bundle Branch Block (RBBB) with QRS duration \> 150ms
2. Previously documented 24-hour ECG holter monitoring with \> 720 poly PVCs/24hours, or non sustained ventricular tachycardia
3. No history of coronary artery disease
4. ST-Segment Elevation Myocardial Infarction (STEMI)
5. Non-ST-Segment Elevation Myocardial Infarction (NSTEMI), according to ESC 2020 guidelines on NSTEMI:

   1. If troponin at t0h is over the "low" criterion on table of the cutoff values
   2. If the change of troponin (Δtroponin) at t1h is over the respective cutoff value at the table for the cutoff values
6. Unstable angina, defined as myocardial ischemia at rest or at minimum effort, in the absence of acute injury/necrosis of myocardial cells
7. Known residual ischemia:

   1. Positive imaging-based stress testing
   2. Negative imaging-based stress testing \>= 1 year, and:

      * History of known coronary artery stenosis \> 60% without revascularization, or
      * PCI \>= 1 year, or
      * CABG \>= 3 years
8. History of acute coronary syndrome within 1 year
9. Severe Aortic Valve Stenosis (mean pressure gradient \> 40mmHg, AVA \< 1cm/m\^2)
10. Severe Chronic Kidney Disease (stage \>= 4)
11. Severe systematic disease, including neoplasmatic disease under any antineoplasmatic treatment, liver failure, infection with fever
12. Use of strategy "pill in the pocket", by taking flecainide (max 200mg) or propafenone (max 600mg) within 6 hours prior to Emergency Department visit
13. Known dysanexia or allergy to flecainide or amiodarone
14. Pregnancy or/and breastfeeding
15. Participation in any other clinical trial
16. Life expectancy less than 1 year
17. Inappropriate, unfit, or unwilling to follow the desingated protocol procedures.

Where this trial is running

Athens and 2 other locations

• First Department of Cardiology, Hippocration General Hospital, National and Kapodistrian University of Athens, Athens, Greece — Athens, Greece (Recruiting)
• Konstantopoulio General Hospital — Athens, Greece (Recruiting)
• KAT General Hospital — Athens, Greece (Recruiting)

Study contacts

• Study coordinator: Konstantinos P Tsioufis, Professor

Conditions Atrial Fibrillation Paroxysmal; Coronary Artery Disease Without Residual Ischemia; Flecainide; Amiodarone