Effect of Eicosapentaenoic Acid/Docosahexaenoic Acid on Coronary High-Intensity Plaques Detected Using Noncontrast T1-weighted Imaging: The AQUAMARINE EPA/DHA Randomized Study.

AIM: Omega-3 fatty acids have emerged as a new option for controlling the residual risk for coronary artery disease (CAD) in the statin era. Eicosapentaenoic acid (EPA) is associated with reduced CAD risk in the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention trial, whereas the Statin Residual Risk with Epanova in High Cardiovascular Risk Patients with Hypertriglyceridemia trial that used the combination EPA/docosahexaenoic acid (DHA) has failed to derive any clinical benefit. These contradictory results raise important questions about whether investigating the antiatherosclerotic effect of omega-3 fatty acids could help to understand their significance for CAD-risk reduction. METHODS: The Attempts at Plaque Vulnerability Quantification with Magnetic Resonance Imaging Using Noncontrast T1-weighted Technic EPA/DHA study is a single-center, triple-arm, randomized, controlled, open-label trial used to investigate the effect of EPA/DHA on high-risk coronary plaques after 12 months of treatment, detected using cardiac magnetic resonance (CMR) in patients with CAD receiving statin therapy. Eligible patients were randomly assigned to no-treatment, 2-g/day, and 4-g/day EPA/DHA groups. The primary endpoint was the change in the plaque-to-myocardium signal intensity ratio (PMR) of coronary high-intensity plaques detected by CMR. Coronary plaque assessment using computed tomography angiography (CTA) was also investigated. RESULTS: Overall, 84 patients (mean age: 68.2 years, male: 85%) who achieved low-density lipoprotein cholesterol levels of ＜100 mg/dL were enrolled. The PMR was reduced in each group over 12 months. There were no significant differences in PMR changes among the three groups in the primary analysis or analysis including total lesions. The changes in CTA parameters, including indexes for detecting high-risk features, also did not differ. CONCLUSION: The EPA/DHA therapy of 2 or 4 g/day did not significantly improve the high-risk features of coronary atherosclerotic plaques evaluated using CMR under statin therapy.

Ongoing challenges for pharmacotherapy for dyslipidemia.

INTRODUCTION: While increasing evidence has led to lipid-modifying therapy achieving an important role in the treatment guidelines for the prevention of cardiovascular disease, these agents are suboptimally used and there remains a considerable risk of clinical events. Accordingly, there is a need to develop more effective lipid-modifying approaches in many patients. AREAS COVERED: A literature search was performed of topical manuscripts focusing on factors influencing use of established therapies and new agents in development that target a range of lipid factors. EXPERT OPINION: More intensive efforts are required to ensure that statin use is maximized in higher risk patients. A range of novel therapies, including proprotein convertase subtilisin kexin-type 9 and cholesteryl ester transfer protein inhibitors, may provide additional protection, although this remains to be established by clinical trials.

Epanova(®) and hypertriglyceridemia: pharmacological mechanisms and clinical efficacy.

While LDL-cholesterol lowering has become the cornerstone of cardiovascular risk reduction strategies, considerable interest in additional targeting of hypertriglyceridemia continues. While ω-3 fatty acids are commonly used in clinical practice for triglyceride lowering, no large-scale clinical trial evaluating their impact on clinical events has been performed. As a result, there remains a lack of consensus with regards to their optimal clinical use. Epanova(®) (Omthera Pharmaceuticals Inc., NJ, USA) is a novel ω-3 free fatty acid formulation, developed to maximize eicosapentenoic acid and docosahexenoic acid bioavailability with low-fat diets, suggesting a potential therapeutic advantage compared with ω-3-acid ethyl esters in the treatment of patients with hypertriglyceridemia. Additional human studies are needed to define more clearly the cellular and molecular basis for the triglyceride-lowering effects of Epanova and this drug's favorable cardiovascular effects, particularly in patients with hypertriglyceridemia.