n-3 Polyunsaturated Fatty Acids (PUFAs) in the Prevention of Atrial Fibrillation

Study Overview
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Brief Summary
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The purpose of this study is to determine the effect of n-3 PUFAs in addition to amiodarone and renin-angiotensin-aldosterone system (RAAS) inhibitors on the maintenance of sinus rhythm after electrical conversion in patients with persistent Atrial fibrillation (AF).

Detailed Description
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Atrial fibrillation (AF) is the most common sustained arrhythmia and represents an increasing burden on the healthcare system. Treatment of AF remains controversial. In patients on antiarrhythmic therapy, the one-year relapse rates of AF after cardioversion ranges from 44% to 77% at one year and amiodarone appears to the be the most effective in maintaining sinus rhythm.Over the last few years, a growing amount of evidences has supported the protective effects of n-3 PUFAs in preventing ventricular arrhythmias and reducing the risk of sudden cardiac death. Furthermore, in the last years, the interest for their possible beneficial role in AF prevention has been increasing.We hypothesized that the administration of n-3 PUFAs could reduce the AF recurrence rate more than amiodarone plus RAAS inhibitors in patients with persistent AF. Therefore the present study aims to evaluate the role of n-3 PUFAs in the prophylaxis of AF recurrences after DCCV in addition to amiodarone and RAS blockers therapy in patients with persistent AF.

Official Title
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N-3 Polyunsaturated Fatty Acids (n-3 PUFAs) in the Prevention of Atrial Fibrillation Recurrences After Electrical Cardioversion. A Prospective Randomized Study.

Conditions
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Atrial Fibrillation

Intervention / Treatment
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* Drug: n-3 PUFAs
* Drug: Placebo
* Drug: RASS inhibitors and/or RAS blockers
* Drug: Amiodarone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: persistent Atrial Fibrillation (AF) lasting > one month history of at least one AF relapse after previous electrical or Pharmacological cardioversion Exclusion Criteria: left atrium size > 6 cm severe valvulopathy myocardial infarction during the previous 6 months unstable angina NYHA heart failure class IV or hemodynamic instability cardiac surgery during the previous 3 months significant pulmonary thyroid and hepatic disease contraindications to treatment with amiodarone or RASS inhibitors chronic renal dysfunction QT > 480 msec in the absence of bundle-branch block bradycardia < 50 b/min diagnosis of paroxysmal AF hyperkalemia pregnancy any disease or other medical treatment that, in the opinion of the investigators, could interfere with the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: n-3 PUFAs<br> | Drug: n-3 PUFAs<br>* 1.0 g of EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in the average ratio EPA/DHA of 0.19:1.5, one capsule twice a day<br>* Other names: OMACOR;Drug: RASS inhibitors and/or RAS blockers<br>* Patients on ACE-Is or ARBs were continued on the same agent. In those who were not on therapy, an ACE-I or an ARB was started. In all patients, an effort was made to achieve the highest tolerated dose.<br>* Other names: renin-angiotensin-aldosterone system inhibitor;Drug: Amiodarone<br>* Patients on amiodarone were continued at a maintenance dose of 200 mg daily, whereas those who were not taking amiodarone were started at a dose of 400 mg daily for 1 week and then continued on a maintenance dose of 200 mg daily.<br>|
| Placebo Comparator: placebo<br> | Drug: Placebo<br>* 1.0 g of olive oil,one capsule twice a day<br>Drug: RASS inhibitors and/or RAS blockers<br>* Patients on ACE-Is or ARBs were continued on the same agent. In those who were not on therapy, an ACE-I or an ARB was started. In all patients, an effort was made to achieve the highest tolerated dose.<br>* Other names: renin-angiotensin-aldosterone system inhibitor;Drug: Amiodarone<br>* Patients on amiodarone were continued at a maintenance dose of 200 mg daily, whereas those who were not taking amiodarone were started at a dose of 400 mg daily for 1 week and then continued on a maintenance dose of 200 mg daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probability of Maintenance of Sinus Rhythm at One-year Follow up.(Number of Patients Who Maintained Sinus Rhythm) | Sinus Rhythm maintenance means no Atrial Fibrillation recurrence at one-year follow up. Patients with successful electrical cardioversion (DCCV)underwent weekly clinical and electrocardiographic controls for the first three weeks following cardioversion. Subsequently, follow up visits with performance of clinical evaluation, ECG, and a 24-hour Holter monitoring were performed at 1, 3, 6 and 12 months after DCCV. | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Mean Time to a First Recurrence of AF and the Rate of AF Recurrence | The mean time to a first recurrence of AF; and the rate of AF recurrence at 1, 3 and 6 months. | 1, 3 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PUFA atrial fibrillation