omacor and eicosapentaenoic-acid-ethyl-ester

Hypertriglyceridemia (triglycerides > 150 mg/dL) affects ~25 % of the United States (US) population and is associated with increased cardiovascular risk. Severe hypertriglyceridemia (≥ 500 mg/dL) is also a risk factor for pancreatitis. Three omega-3 fatty acid (OM3FA) prescription formulations are approved in the US for the treatment of adults with severe hypertriglyceridemia: (1) OM3FA ethyl esters (OM3EE), a mixture of OM3FA ethyl esters, primarily eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Lovaza®, Omtryg™, and generics); (2) icosapent ethyl (IPE), EPA ethyl esters (Vascepa®); and (3) omega-3 carboxylic acids (OM3CA), a mixture of OM3FAs in free fatty acid form, primarily EPA, DHA, and docosapentaenoic acid (Epanova®). At approved doses, all formulations substantially reduce triglyceride and very-low-density lipoprotein levels. DHA-containing formulations may also increase low-density lipoprotein cholesterol. However, this is not accompanied by increased non-high-density lipoprotein cholesterol, which is thought to provide a better indication of cardiovascular risk in this patient population. Proposed mechanisms of action of OM3FAs include inhibition of diacylglycerol acyltransferase, increased plasma lipoprotein lipase activity, decreased hepatic lipogenesis, and increased hepatic β-oxidation. OM3CA bioavailability (area under the plasma concentration-time curve from zero to the last measurable concentration) is up to 4-fold greater than that of OM3FA ethyl esters, and unlike ethyl esters, the absorption of OM3CA is not dependent on pancreatic lipase hydrolysis. All three formulations are well tolerated (the most common adverse events are gastrointestinal) and demonstrate a lack of drug-drug interactions with other lipid-lowering drugs, such as statins and fibrates. OM3FAs appear to be an effective treatment option for patients with severe hypertriglyceridemia.

Topics: Adult; Biological Availability; Cholesterol, LDL; Diacylglycerol O-Acyltransferase; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Esters; Fatty Acids, Omega-3; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Lipogenesis; Lipoprotein Lipase; Lipoproteins, VLDL; Liver; Oxidation-Reduction; Triglycerides

Patients with elevated triglycerides (TG) may be at a higher risk for cardiovascular (CV) disease. Omega-3 fatty acids (OM3FAs), particularly the long-chain fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), effectively reduce TG and thus may impact CV outcomes; however, clinical data have been inconsistent. This review discusses the efficacy, safety, and key considerations of currently approved prescription OM3FA products in patients with elevated TG with or without concomitant elevations in other atherogenic parameters. Currently, 6 prescription OM3FA formulations are approved in the United States: omega-3-acid ethyl esters (Lovaza, Omtryg, and 2 generic formulations), omega-3-carboxylic acids (Epanova), which contain both EPA and DHA, and icosapent ethyl (Vascepa), which is an EPA-only formulation. All prescription OM3FA products effectively lower TG, with the magnitude of TG reduction affected by baseline TG level. Products that contain DHA can raise levels of low-density lipoprotein cholesterol, which is of particular concern in patients with atherosclerosis; Vascepa, however, does not raise these levels and therefore provides these patients with another option. Long-term outcomes trials for Vascepa (ongoing) and Epanova (planned) will help clarify the potential CV benefits in patients with persistent hypertriglyceridemia despite statin therapy.

Topics: Cholesterol, LDL; Dietary Supplements; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; Hypertriglyceridemia; Hypolipidemic Agents

Topics: Animals; Clinical Trials as Topic; Dietary Supplements; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; Hypertriglyceridemia; Severity of Illness Index; Triglycerides

To examine n-3 polyunsaturated fatty acid (PUFA) incorporation into atherosclerotic plaques and the association with plaque inflammation and stability.. Patients awaiting carotid endarterectomy (n=121) were randomised to consume control capsules or n-3 PUFA ethyl ester capsules until surgery (median 21 days). The fatty acid compositions of plasma and carotid plaque phospholipids, plaque features, and expression of inflammatory genes were determined. The proportion of eicosapentaenoic acid (EPA) was higher (P<0.0001) in carotid plaque phospholipids in patients in the n-3 PUFA group. Plaques from patients in the n-3 PUFA group had fewer foam cells (P=0.0390). There were no other differences between plaques in the two groups with regard to histological characteristics or morphology. Plaque stability was not different between the two groups. However, the EPA content of plaque phospholipids was inversely associated with plaque instability (P=0.0209), plaque inflammation (P=0.0108), the number of T cells in the plaque (P=0.0097) and a summary score considering a range of plaque features (P=0.0425). Plaques from patients who received n-3 PUFAs had significantly lower levels of mRNA for matrix metalloproteinases (MMP)-7 (P=0.0055), -9 (P=0.0048) and -12 (P=0.0044) and for interleukin-6 (P=0.0395) and intercellular adhesion molecule 1 (P=0.0142).. Atherosclerotic plaques readily incorporate EPA. A higher plaque EPA content is associated with a reduced number of foam cells and T cells, less inflammation and increased stability.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Capsules; Carotid Artery Diseases; Chi-Square Distribution; Cytokines; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Endarterectomy, Carotid; England; Female; Foam Cells; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators; Male; Matrix Metalloproteinases; Middle Aged; Phospholipids; Preoperative Care; RNA, Messenger; Rupture, Spontaneous; T-Lymphocytes; Treatment Outcome

In patients with dyslipidemia, elevated triglyceride (TG) levels, or TG-rich lipoproteins, and cardiovascular risk may remain despite statin therapy. Prescription omega-3 fatty acid formulations containing the ethyl esters of eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA) (omega-3-acid ethyl esters; Lovaza®) or high-purity EPA ethyl ester (icosapent ethyl; Vascepa®) are TG-lowering treatments that may be administered in addition to statins. Here we describe the effects of switching from omega-3-acid ethyl esters to icosapent ethyl in a 44-year-old obese man with dyslipidemia, hypertension, and hypothyroidism. The patient was receiving stable treatment with medications, including atorvastatin 40 mg/day and extended-release niacin 1000 mg/day. Owing to persistently elevated TG levels and other cardiovascular risk factors, the patient was initiated on omega-3-acid ethyl esters 4 g/day. After approximately 2 years on omega-3-acid ethyl esters, his total cholesterol (TC) level was 184 mg/dL, low-density lipoprotein cholesterol (LDL-C) level was 81 mg/dL, TG level was elevated at 307 mg/dL despite statin therapy, and non-high-density lipoprotein cholesterol (non-HDL-C) level was 144 mg/dL. After the switch to icosapent ethyl, TC level decreased by 34% to 121 mg/dL, LDL-C level decreased by 28% to 58 mg/dL, TG level decreased by 41% to 180 mg/dL, and non-HDL-C level decreased by 44% to 81 mg/dL. Switching from omega-3-acid ethyl esters containing both EPA and DHA to icosapent ethyl containing high-purity EPA resulted in beneficial and substantial changes in the lipid profile with a notable reduction of TG levels along with additional reductions in LDL-C levels in a statin-treated obese patient with persistently high TG levels. Treatment with icosapent ethyl was well tolerated.

Topics: Adult; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Esters; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Hypertriglyceridemia; Hypothyroidism; Lipids; Male; Risk Factors

Metabolic syndrome is implicated in the decline of cognitive ability. We investigated whether the prescription n-3 fatty acid administration improves cognitive learning ability in SHR.Cg-Lepr(cp)/NDmcr (SHR-cp) rats, a metabolic syndrome model, in comparison with administration of eicosapentaenoic acid (EPA, C20:5, n-3) alone. Administration of TAK-085 [highly purified and concentrated n-3 fatty acid formulation containing EPA ethyl ester and docosahexaenoic acid (DHA, C22:6, n-3) ethyl ester] at 300 mg/kg body weight per day for 13 weeks reduced the number of reference memory-related errors in SHR-cp rats, but EPA alone had no effect, suggesting that long-term TAK-085 administration improves cognitive learning ability in a rat model of metabolic syndrome. However, the working memory-related errors were not affected in either of the rat groups. TAK-085 and EPA administration increased plasma EPA and DHA levels of SHR-cp rats, associating with an increase in EPA and DHA in the cerebral cortex. The TAK-085 administration decreased the lipid peroxide levels and reactive oxygen species in the cerebral cortex and hippocampus of SHR-cp rats, suggesting that TAK-085 increases antioxidative defenses. Its administration also increased the brain-derived neurotrophic factor levels in the cortical and hippocampal tissues of TAK-085-administered rats. The present study suggests that long-term TAK-085 administration is a possible therapeutic strategy for protecting against metabolic syndrome-induced learning decline.

Topics: Animals; Brain-Derived Neurotrophic Factor; Cerebral Cortex; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Hippocampus; Lipid Peroxides; Male; Maze Learning; Memory; Metabolic Syndrome; Rats; Rats, Inbred SHR

Deposition of amyloid β peptide (Aβ) into the brain causes cognitive impairment. We investigated whether prescription pre-administration of n-3 fatty acids improves cognitive learning ability in young rats and whether it protects against learning ability impairments in an animal model of Alzheimer's disease that was prepared by infusion of Aβ(1-40) into the cerebral ventricles of rats. Pre-administration of TAK-085 (highly purified and concentrated n-3 fatty acids containing eicosapentaenoic acid ethyl ester and docosahexaenoic acid ethyl ester) at 300 mg kg(-1) day(-1) for 12 weeks significantly reduced the number of reference memory errors in an 8-arm radial maze, suggesting that long-term administration of TAK-085 improves cognitive leaning ability in rats. After pre-administration, the control group was divided into the vehicle and Aβ-infused groups, whereas the TAK-085 pre-administration group was divided into the TAK-085 and TAK-085 + Aβ groups (TAK-085-pre-administered Aβ-infused rats). Aβ(1-40) or vehicle was infused into the cerebral ventricle using a mini osmotic pump. Pre-administration of TAK-085 to the Aβ-infused rats significantly suppressed the number of reference and working memory errors and decreased the levels of lipid peroxide and reactive oxygen species in the cerebral cortex and hippocampus of Aβ-infused rats, suggesting that TAK-085 increases antioxidative defenses. The present study suggests that long-term administration of TAK-085 is a possible therapeutic agent for protecting against Alzheimer's disease-induced learning deficiencies.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Cerebral Cortex; Cerebral Ventricles; Cognition Disorders; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Hippocampus; Lipid Peroxides; Male; Maze Learning; Rats; Rats, Wistar; Reactive Oxygen Species

Topics: Administration, Oral; Capsules; Carotid Artery Diseases; Dietary Supplements; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Endarterectomy, Carotid; Foam Cells; Gene Expression Regulation; Humans; Inflammation; Inflammation Mediators; Matrix Metalloproteinases; Phospholipids; Preoperative Care; Rupture, Spontaneous; T-Lymphocytes; Treatment Outcome