The Effects of Lovaza® in Acute Myocardial Infarction

Atherosclerotic cardiovascular disease is the cause for over 19 million deaths in the US
annually with coronary artery disease accounting for most of this mortality burden.1 Despite
major advances in the treatment of coronary heart disease patients, a large number of victims
of the disease who are apparently healthy die suddenly without prior symptoms. For those who
arrive alive at an emergency department, a benefit is accrued from an orchestrated program of
live-saving therapeutics designed to preserve ischemic or infarcted myocardium and prevent
ventricular arrhythmias. However, despite improvements in door-to-balloon (angioplasty) times
in the past decade, reductions in in-hospital mortality have not materialized.2 Average
30-day mortality from ST elevation MI has been shown to be approximately 7% despite the
modern aggressive approach of utilizing acute pharmacologic and percutaneous interventions as
well as a comprehensive approach to risk factor modification.3 Antiplatelet agents including
aspirin, clopidogrel, heparin, and IIb/IIIa inhibitors represent stalwart components of the
acute coronary syndrome therapeutic treatment program. At the same time, the safety of
combination antiplatelet agents used acutely and chronically in individuals with an acute
coronary syndrome is concerning as bleeding complications can result in serious,
life-threatening consequences.4 Studies have shown that patients treated with the combination
of aspirin and clopidogrel have a small but significant increased risk of major and minor
bleeding compared to each agent alone.4-6 In contrast, the use of fish oil in conjunction
with aspirin and clopidogrel in patients with cardiovascular disease followed for an average
of 33 months has been shown to have no significant effect on risk of major and minor bleeding
compared to those on aspirin and clopidogrel alone, with a trend toward a reduced risk of
minor bleeding in those taking fish oil.4 In Preliminary Data it is shown that a robust
synergistic effect between Lovaza® and aspirin on the downregulation of platelet function may
occur. These data suggest that the most potent omega-3 fatty acids found in fish oil
(eicosapentaenoic acid {EPA} and docosahexaenoic acid {DHA}) act acutely to modulate a major
contributor to the pathophysiology of acute coronary syndromes. This study will randomize 60
patients with ST elevation myocardial infarction to treatment with Lovaza® or placebo and
measure the differences in platelet function and electrophysiologic parameters between
treatment arms during their acute hospitalization and 1 week after discharge.

Inclusion Criteria:

- Acute myocardial infarction documented by at least 2 of the following:

1. Typical symptoms

2. Abnormal levels of cardiac biomarkers (troponin I or T or CK-MB mass) with at
least one determination > 99th percentile or ULN for the laboratory

3. ECG findings diagnostic of myocardial infarction based on the American College of
Cardiology criteria.

- Status-post urgent or emergent PCI

- Have a Thrombolysis In Myocardial Infarction (TIMI) flow grade = 3 (complete
perfusion) post PCI.

- Have the capacity for informed consent (e.g. without significant dementia or sedation
from medication)

- Ingested 325 mg of chewed aspirin as part of the acute coronary syndrome treatment
protocol.

Exclusion Criteria:

- No informed consent

- Daily aspirin use prior to index hospitalization

- Known prior myocardial infarction

- Known pregnancy

- Known allergy to fish, fish oil, or aspirin

- Known active internal or non-superficial bleeding, known bleeding disorder,
coagulation defect, or thrombocytopenia

- Thrombolysis in the past 12 hours

- Treatment with a IIbIIIa inhibitor during index hospitalization

- Cardiogenic shock or symptomatic hypotension or sitting SBP < 95 mmHg

- Severe uncontrolled hypertension (≥180/110) or hypertensive retinopathy

- A history of major surgery, trauma, retinal hemorrhage, significant gastrointestinal
(not hemorrhoidal) or genitourinary bleeding in the past 6 weeks

- A history of cerebrovascular attack within two years, or cerebrovascular attack with a
significant residual neurological deficit

- A known arteriovenous malformation or aneurysm

- Severe liver insufficiency (ALT ≥ 3 times normal)

- Renal insufficiency requiring dialysis

- A known diagnosis of vasculitis

- Participation in another clinical study

- History of malignancy, except subjects who have been disease-free for greater than 10
years, or whose only malignancy has been basal or squamous cell skin carcinoma

- Oral contraceptive use

- Daily use of NSAIDs

- History of drug or alcohol abuse, or current weekly alcohol consumption >14 units/week
(1 unit = 1 beer, 1 glass of wine, 1 mixed cocktail containing 1 shot of alcohol)