Effect of Vascepa on Progression of Coronary Atherosclerosis in Persons with Elevated Triglycerides (200-499) on Statin Therapy. The study is to determine progression rates of low attenuation plaque under influence of Vascepa as compared to placebo.

Residual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive statin therapy, underscoring the need for additional intervention. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into membrane phospholipids and atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through rupture. EPA also improves atherogenic dyslipidemia characterized by reduction of triglycerides without raising low-density lipoprotein cholesterol. All of this data supports the biologic plausibility of EPA as an anti-atherosclerotic agent. The goal of this study is to evaluate whether treatment with Vascepa (4 grams) results in a greater change from baseline in low attenuation plaque than placebo in subjects with elevated triglycerides (200-499 mg/dl).

Inclusion Criteria:

• Elevated triglycerides (fasting value between 200-499 mg/dl) at qualifying or baseline visit.
• LDL-C ≤115 mg/dL on appropriate statin therapy
• LDL-C >40 mg/dL
• Stable diet and exercise, as defined as the same pattern for the previous 4 weeks
• Stable treatment with a statin+/- ezetimibe for at least 4 weeks
• Patients with at least 1 angiographic stenosis with at least 20% narrowing by coronary computed tomography angiography (CTA).
• Willingness to be on birth control for women of childbearing age or established post-menopausal

Exclusion Criteria:

• A contraindication to fish or fish oils including: known hypersensitivity to drug or fish.
• Any unstable medical, psychiatric or substance abuse disorder that in the opinion of the investigator or principal investigator is likely to affect the subject's ability to complete the study or precludes the subject's participation in the study.
• Non-study lipid altering medications or supplements (ie - Niacin, PCSK9, fibrates, bile acid Sequestrants, dietary fish oil supplement capsules, orlistat [OTC (Alli®) as well as Rx (Xenical®)] or other drugs used for weight loss).
• Stable (same daily dose for the last 4 weeks) on medications that can affect lipids (retinoids, hormones, steroids, HIV medications, chemotherapy, thyroid medications).
• BMI > 40
• Bleeding disorder
• Uncontrolled hypertension (SBP≥ 180 mmHg or DBP≥100 mmHg)
• History of known myocardial infarction, stroke or life-threatening arrhythmia within the prior six months.
• NYHA Class III- IV heart failure
• History of malignancy within the last 5 years (other than skin cancer) or evidence of active cancer which would require concomitant cancer chemotherapy.
• Serum creatinine > 1.4 mg/dl
• Drug or alcohol abuse, or current intake of more than 14 ounces of alcohol per week for men and 10 ounces for women
• Concurrent enrollment in another placebo-controlled trial or within 30 days of finishing another trial
• Partial ileal bypass or known gastrointestinal disease limiting drug absorption
• History of hypertensive encephalopathy or cerebrovascular accident
• Hematological or biochemical values at screening outside the reference ranges considered as clinically significant in the opinion of the investigator or PI
• Pregnancy
• Genetic mutations/polymorphisms having an effect on blood lipids
• History of coronary artery bypass surgery
• Allergy to contrast material
• Allergy to beta-blocker in subjects with resting heart rate >70 bpm

Data will be tabulated and analysed. Study site will not share any of the subject identifiers.