Evaluating the Effectiveness of Fish Oil Supplements at Reducing the Recurrence of Atrial Fibrillation

AF is the most common type of serious heart arrhythmia. It affects approximately 2% of the
population and is becoming more common. In AF, the heart's atria, or upper chambers,
contract in a very disorganized and abnormal manner and are unable to correctly pump blood
into the heart's ventricles, or lower chambers. Symptoms may include a rapid or irregular
pulse, dizziness, fainting, or breathing difficulty. Recent studies suggest that
inflammation plays a fundamental role in the development of AF. Inflammation, and the
resulting oxidative stress, can cause cellular and tissue damage. In turn, this may alter
heart function, potentially leading to both the onset and recurrence of AF. Markers of
inflammation, such as C-reactive protein (CRP) and interleukin-6 (IL-6), are often elevated
in patients with AF, providing further evidence of inflammation's role. While there are
several treatment options for AF, they are usually only moderately effective. Previous
research has shown that fish oil supplements have anti-inflammatory, antifibrotic, and
antioxidant effects and can reduce the risk of AF following surgery. However, it is not
known exactly how fish oil reduces this risk and whether the same positive effect will carry
over in people who experience the more common type of AF that is unrelated to surgery. The
purpose of this study is to evaluate the effectiveness of fish oil supplementation at
decreasing the recurrence of AF in adults who have not undergone recent surgery. Researchers
will also examine the ways in which fish oil reduces AF recurrence.

This study will enroll people who have had at least two occurrences of AF. Participants will
be randomly assigned to receive either fish oil supplements or placebo for 24 weeks. At
study visits at baseline and Weeks 2, 4, 8, 12, 18, and 24, participants will undergo a
medical and social history review, a physical exam, and blood and urine collection. At the
baseline study visit, an electrocardiogram will also occur.

Inclusion Criteria:

- >=21 years of age

- a history of atrial fibrillation

- a history of at least two occurrences of atrial fibrillation or atrial flutter, at
least one of which is atrial fibrillation

- an electrocardiogram that was recorded within 12 months of randomization showing
atrial fibrillation or atrial flutter

- sinus rhythm at the time the first dose of randomized medication is taken

- stable antiarrhythmic medications

- if the patient has had an ablation for atrial fibrillation or flutter or a MAZE
procedure, the qualifying episode of atrial fibrillation must have occurred at least
3 months post-procedure

- normal serum potassium level within the last 28 days

- provided informed consent

Exclusion Criteria:

- permanent atrial fibrillation or flutter

- New York Heart Association class III or IV heart failure or Canadian Cardiovascular
Society class III or IV angina pectoris

- cardiac or thoracic surgery within the previous 3 months

- acute pericarditis within the previous 3 months

- other reversible causes of atrial fibrillation such as thyrotoxicosis

- acute myocardial infarction or unstable angina within the previous 3 months

- history of neurologic event (TIA or stroke)within the past 3 months

- history of acute congestive heart failure precipitated by atrial fibrillation, and
the patient is not receiving rate-control therapy

- Wolff-Parkinson-White syndrome

- a medical condition that is likely to be fatal in less than one year

- active, uncontrolled co-morbid inflammatory condition (e.g., rheumatoid arthritis,
inflammatory bowel disease, SLE)

- receiving cytotoxic chemotherapy or radiotherapy for cancer

- taking a fish oil supplement

- allergic to fish

- bleeding event not related to trauma or surgery requiring hospitalization or
transfusion in previous year

- systolic blood pressure < 90 mm Hg or heart rate <50 beats/minute

- history of ventricular fibrillation or sustained ventricular tachycardia, or presence
of an implanted defibrillator placed for the occurrence of such an event or the
presence of ICD that has discharged appropriately for a ventricular arrhythmia

- pregnant or breast feeding

- enrollment in another research study involving an intervention

- on dialysis or recipient of a renal transplant

- use of potentially cardiotoxic illegal drugs (cocaine, methamphetamine, opioids) in
the last 12 months

- Treated for alcoholism and currently drinking alcohol to excess or alcoholic
cardiomyopathy as the primary clinical diagnosis and currently drinking alcohol to
excess

- presence of an iron-storage disease, such as hemochromatosis, transfusional
hemosiderosis, or those subjects in whom a daily dose of up to 20 mg elemental iron
(in and of itself or in addition of current iron supplementation) would post a risk
for toxicity from iron overload

- subjects receiving or anticipated to receive intravenous iron thearpy