Eicosapentaenoic Acid Improves Endothelial Nitric Oxide Bioavailability Via Changes in Protein Expression During Inflammation.

Background: Endothelial cell (EC) dysfunction involves reduced nitric oxide (NO) bioavailability due to NO synthase uncoupling linked to increased oxidation and reduced cofactor availability. Loss of endothelial function and NO bioavailability are associated with inflammation, including leukocyte activation. Eicosapentaenoic acid (EPA) administered as icosapent ethyl reduced cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) in relation to on-treatment EPA blood levels.

Eicosapentaenoic acid (EPA) reduces pulmonary endothelial dysfunction and inflammation due to changes in protein expression during exposure to particulate matter air pollution.

Aims: Inhalation of air pollution small particle matter (PM) is a leading cause of cardiovascular (CV) disease. Exposure to PMs causes endothelial cell (EC) dysfunction as evidenced by nitric oxide (NO) synthase uncoupling, vasoconstriction and inflammation. Eicosapentaenoic acid (EPA) has been shown to mitigate PM-induced adverse cardiac changes in patients receiving omega-3 fatty acid supplementation.

Fish oil supplementation during pregnancy and postpartum in mothers with overweight and obesity to improve body composition and metabolic health during infancy: A double-blind randomized controlled trial.

Background: Maternal obesity during pregnancy is associated with an increased risk of obesity and metabolic disease in the offspring. Supplementation with fish oil (FO), which is insulin sensitizing, during pregnancy in mothers with overweight or obesity may prevent the development of greater adiposity and metabolic dysfunction in their children.

Objectives: To determine the effects of FO supplementation throughout the second half of pregnancy and lactation in mothers with overweight or obesity on infant body composition and metabolism.

Potential effects of icosapent ethyl on cardiovascular outcomes in cigarette smokers: REDUCE-IT smoking.

Aims: Cigarette smoking is among the most well-established risk factors for adverse cardiovascular outcomes. We sought to determine whether icosapent ethyl (IPE), a highly purified form of eicosapentaenoic acid with antiatherothrombotic properties, may reduce the excessive risk of cardiovascular disease (CVD) attributable to smoking.

Methods And Results: Reduction of Cardiovascular Events with Icosapent Ethyl Trial (REDUCE-IT) was a multinational, double-blind trial that randomized 8179 statin-treated patients with elevated triglycerides and CV risk to IPE or placebo, with a median follow-up period of 4.

Benefits of icosapent ethyl for enhancing residual cardiovascular risk reduction: A review of key findings from REDUCE-IT.

REDUCE-IT was a multinational, double-blind trial that randomized 8179 statin-treated patients with controlled low-density lipoprotein cholesterol and moderately elevated triglycerides to icosapent ethyl (IPE) or placebo. IPE was associated with a substantial reduction in the primary composite endpoint of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. Since the original publication of the trial, there have been a myriad of additional analyses confirming the benefit of IPE in various patient groups.

Cholesterol crystals and atherosclerotic plaque instability: Therapeutic potential of Eicosapentaenoic acid.

Atherosclerotic plaques associated with acute coronary syndromes (ACS), i.e. culprit lesions, frequently feature a ruptured fibrous cap with thrombotic complications.

Effects of Randomized Treatment With Icosapent Ethyl and a Mineral Oil Comparator on Interleukin-1β, Interleukin-6, C-Reactive Protein, Oxidized Low-Density Lipoprotein Cholesterol, Homocysteine, Lipoprotein(a), and Lipoprotein-Associated Phospholipase A2: A REDUCE-IT Biomarker Substudy.

Background: REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial) reported a 25% relative risk reduction in major adverse cardiovascular events with use of icosapent ethyl compared with pharmaceutical grade mineral oil. The mechanisms underlying this benefit remain uncertain. We explored whether treatment allocation in REDUCE-IT might affect a series of biomarkers in pathways known to associate with atherosclerosis risk.

Omega-3-fatty acids: Do they prevent cardiovascular disease?

Despite cardiovascular disease (CVD) reductions with high-intensity statins, there remains residual risk among patients with metabolic disorders. Alongside low-density lipoproteins (LDL-C), elevated triglycerides (TG) are associated with incident CVD events. Omega-3 fatty acids (n3-FAs), specifically eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), lower TG levels, but their ability to reduce CV risk has been highly inconsistent.

A biological rationale for the disparate effects of omega-3 fatty acids on cardiovascular disease outcomes.

The omega-3 fatty acids (n3-FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) rapidly incorporate into cell membranes where they modulate signal transduction pathways, lipid raft formation, and cholesterol distribution. Membrane n3-FAs also form specialized pro-resolving mediators and other intracellular oxylipins that modulate inflammatory pathways, including T-cell differentiation and gene expression. Cardiovascular (CV) trials have shown that EPA, administered as icosapent ethyl (IPE), reduces composite CV events, along with plaque volume, in statin-treated, high-risk patients.

Icosapent Ethyl Reduces Ischemic Events in Patients With a History of Previous Coronary Artery Bypass Grafting: REDUCE-IT CABG.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery.

Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl-Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo.

Benefits of Icosapent Ethyl Across the Range of Kidney Function in Patients With Established Cardiovascular Disease or Diabetes: REDUCE-IT RENAL.

Background: Chronic kidney disease is associated with adverse outcomes among patients with established cardiovascular disease (CVD) or diabetes. Commonly used medications to treat CVD are less effective among patients with reduced kidney function.

Methods: REDUCE-IT (Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial) was a multicenter, double-blind, placebo-controlled trial that randomly assigned statin-treated patients with elevated triglycerides (135-499 mg/dL) who had CVD or diabetes and 1 additional risk factor to treatment with icosapent ethyl (4 g daily) or placebo.

Omega-3 and omega-6 fatty acids have distinct effects on endothelial fatty acid content and nitric oxide bioavailability.

Treatment with high dose icosapent ethyl (IPE), an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA), significantly reduced ischemic events in patients with either cardiovascular disease (CV) or diabetes plus other risk factors (REDUCE-IT) but the mechanism is not well understood.  We compared the effects of EPA, docosahexaenoic acid (DHA), and the omega-6 fatty acid arachidonic acid (AA) on bioavailability of nitric oxide (NO) and fatty acid composition. Human umbilical vein endothelial cells (HUVECs) were pretreated with EPA, DHA, or AA (10 µM).

A randomized trial of icosapent ethyl in ambulatory patients with COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic remains a source of considerable morbidity and mortality throughout the world. Therapeutic options to reduce symptoms, inflammatory response, or disease progression are limited. This randomized open-label trial enrolled 100 ambulatory patients with symptomatic COVID-19 in Toronto, Canada.

The role of eicosapentaenoic acid in reducing important cardiovascular events, including coronary revascularization.

The omega-3 fatty acid eicosapentaenoic acid has an important role in human health. The Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) examined the prescription omega-3 fatty acid icosapent ethyl (IPE) in patients with established cardiovascular disease (CVD) or with diabetes plus additional CVD risk factors. The trial found a large reduction in CVD events, including significant reductions in CVD death, myocardial infarction, stroke, coronary revascularization, and hospitalization for unstable angina.

EPA and DHA containing phospholipids have contrasting effects on membrane structure.

Omega-3 FAs EPA and DHA influence membrane fluidity, lipid rafts, and signal transduction. A clinical trial, Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial, demonstrated that high-dose EPA (4 g/d icosapent ethyl) reduced composite cardiovascular events in statin-treated high-risk patients. EPA benefits correlated with on-treatment levels, but similar trials using DHA-containing formulations did not show event reduction.

Icosapent ethyl: safely reducing cardiovascular risk in adults with elevated triglycerides.

Introduction: In patients at high cardiovascular risk, the rate of events remains elevated despite traditional, evidence-based lipid-lowering therapy. Residual hypertriglyceridemia is an important contributor to this risk. However, prior medications with triglyceride-lowering effects have not reduced adverse clinical outcomes in the statin era.