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

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).

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.

• Drug: n-3 PUFAs
  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
  Other Name: OMACOR
• Drug: Placebo
  1.0 g of olive oil,one capsule twice a day
  Other Name: Placebo
• Drug: RASS inhibitors and/or RAS blockers
  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.
  Other Name: renin-angiotensin-aldosterone system inhibitor
• Drug: Amiodarone
  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.
  Other Name: Amiodarone

• Active Comparator: n-3 PUFAs
  Interventions:

  • Drug: n-3 PUFAs
  • Drug: RASS inhibitors and/or RAS blockers
  • Drug: Amiodarone
• Placebo Comparator: placebo
  Interventions:

  • Drug: Placebo
  • Drug: RASS inhibitors and/or RAS blockers
  • Drug: Amiodarone

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.