omacor and Hypertriglyceridemia

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

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.

Topics: Biological Availability; Docosahexaenoic Acids; Drug Combinations; Drug Tolerance; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fibric Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Insulin Resistance; Life Style; Lipoproteins; Treatment Outcome; Weight Loss

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

Oral omega-3 ethylester concentrate (omega-3 EEC) [Omacor; Lovaza] is indicated as an adjuvant therapy in adult patients for secondary prevention post-myocardial infarction (MI) and the treatment of hypertriglyceridaemia in the majority of European countries, and for the treatment of hypertriglyceridaemia (serum triglyceride levels > or =5.6 mmol/L [> or =500 mg/dL]) in the US. Each 1000 mg capsule of omega-3 EEC consists of 460 mg of ethyl eicosapentaenoic acid and 380 mg of ethyl docosahexaenoic acid. The addition of omega-3 EEC 1000 mg/day to standard medical therapy in the GISSI-Prevenzione study provided secondary prevention benefits in post-MI adult patients. The benefits were attributable to reductions in death and cardiovascular death (including sudden death). Additional data examining the extent and mechanisms of the cardiovascular benefit conferred by omega-3 EEC in secondary prevention would be useful. As an adjunct to diet, monotherapy with omega-3 EEC 4000 mg/day significantly reduced triglyceride levels in patients with hypertriglyceridaemia, although limited data suggest it was less effective than gemfibrozil. In addition, omega-3 EEC 4000 mg/day plus simvastatin or atorvastatin reduced triglyceride, non-high-density lipoprotein cholesterol (non-HDL-C) and/or very-low-density lipoprotein cholesterol (VLDL-C) levels to a significantly greater extent than placebo plus simvastatin or atorvastatin. Omega-3 EEC was generally well tolerated both as secondary prevention post-MI and in the treatment of hypertriglyceridaemia. Thus, omega-3 EEC is a useful option both in secondary prevention post-MI and the treatment of hypertriglyceridaemia.

Topics: Adult; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Humans; Hypertriglyceridemia; Myocardial Infarction; Randomized Controlled Trials as Topic; Secondary Prevention; Treatment Outcome

Despite progress made in post-myocardial infarction (MI) revascularization and background therapy for the failing heart, the prevention of adverse cardiac remodeling associated with severe rhythm disorders remains an important drug target. Part of the remodeling can be counteracted by modulating the activity of ion channels and exchangers by omega-3 acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). In the GISSI-Prevenzione and GISSI-HF trials, omega-3 fatty acids were administered as ethyl esters (Omacor Solvay Pharmaceuticals) and not as triglycerides present in fish oil. Ethyl esters result in a sustained intestinal absorption of EPA and DHA and require various purification steps during production, thereby minimizing the content of environmental toxins. Also the rather high (38%) DHA content of Omacor should not be ignored since in rats with low dose intake of omega-3 acids, DHA but not EPA inhibited ischemia-induced arrhythmias. In patients on multiple tablets, 840 mg EPA+DHA in one capsule is preferred to increase compliance. It is not justified to refer to Omacor as "n-3 polyunsaturated fatty acid supplementation" or even "fish oil" and, based on controlled clinical trials, there is no evidence that fish oil could be a substitute of Omacor. To avoid further confusion, guidelines should be precise and refer to the medication, eg, as in NICE guideline CG48: "Omega-3-acid ethyl esters treatment licensed for secondary prevention post-MI." The anti-arrhythmogenic action of Omacor should be seen in the context of implantable cardioverter-defibrillator trials (DINAMIT, IRIS) where non-sudden death was increased and total mortality unaltered. However, Omacor administered in the GISSI-HF trial reduced the incidence of severe arrhythmic events and mortality. Also in the GISSI-Prevenzione trial, arrhythmic death and mortality were reduced. At higher dosages (daily, 3-4 g) Omacor exhibits more pronounced cardiovascular benefits and, as a licensed indication, improves hypertriglyceridemia and related lipid parameters.

Topics: Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Cardiovascular Diseases; Clinical Trials as Topic; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Heart Failure; Humans; Hypertriglyceridemia; Hypoglycemic Agents; Medication Adherence; Myocardial Infarction

Triglyceride (TG) levels can increase for numerous reasons, including a sedentary lifestyle, an unhealthy diet, especially one rich in refined carbohydrates, and comorbidities. According to the National Cholesterol Education Program (NCEP), the normal TG level is < 150 mg/dL. Patients with very high TG (VHTG) levels (> or = 500 mg/dL) should be promptly managed and treated to reach lipid treatment goals, as determined by the NCEP. Lowering TG levels is the primary management goal in these patients, while lowering low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol levels are secondary goals. Therapeutic lifestyle changes are often recommended initially for patients with elevated TGs; however, concomitant drug therapy is often required. Data show that intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can significantly decrease serum TGs, along with plasma concentrations of certain lipoproteins. Omega-3-acid ethyl esters are available by prescription or as dietary supplements. Clinical trials in adult patients with VHTGs show that four 1 g capsules of prescription omega-3 fatty acids, which contain 465 mg of EPA and 375 mg of DHA per capsule, can effectively decrease TG levels by up to 45%, and is generally well tolerated.

Topics: Diet; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Humans; Hypertriglyceridemia; Triglycerides

A reliable means of treating hyper-triglyceridemia is the use of large doses of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Modest levels of EPA and DHA may be obtained from food, particularly fatty fish.. This article is intended to review clinically relevant differences between dietary-supplement omega-3 fatty acids and prescription omega-3-acid ethyl esters (P-OM3).. PubMed and the Food and Drug Administration (FDA) Website were searched for articles published between 1995 and 2007 that contained the terms fish oil, fatty acids, n-3 fatty acids, omega fatty acids, docosahexaenoic acid, or eicosapentaenoic acid. Articles discussing sources, recommended intake, and differences among various formulations of omega-3 fatty acids were selected for review. A limitation to this review is the lack of head-to-head clinical trials using P-OM3 and dietary-supplement omega-3 fatty acids.. Many types of nonprescription dietary supplements of omega-3 fatty acids are available; however, the efficacy, quality, and safety of these products are open to question because they are not regulated by the same standards as pharmaceutical agents. P-OM3 is the only omega-3 fatty acid product (Omacor capsules) approved by the US FDA available in the United States as an adjunct to diet to reduce very high (> or = 500 mg/dL) triglyceride levels in adult patients.. P-OM3 can be used with confidence by practitioners who want to provide therapeutic doses of omega-3 fatty acids in a preparation that has been documented to be both safe and effective.

Topics: Dietary Supplements; Docosahexaenoic Acids; Drug Combinations; Drug Prescriptions; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Food; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Nonprescription Drugs; Nutrition Policy

Omacor (omega-3-acid ethyl esters; Reliant Pharmaceuticals, Inc., Liberty Corner, NJ) is a highly purified, prescription omega-3 fatty acid formulation with high concentrations of eicosapentaenoic acid (EPA) (465 mg) and docosahexaenoic acid (DHA) (375 mg) in each 1-g capsule, along with 4 mg (6 IU) of vitamin E. At a typical dose of 4 capsules/day, Omacor significantly lowers plasma triglyceride levels either as monotherapy or in combination with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) or fibrates. Omacor also modestly increases plasma levels of low-density lipoprotein cholesterol, increases high-density lipoprotein cholesterol levels, and has favorable effects on lipoprotein particle size and subclass distribution. Omacor is well tolerated, with few side effects other than mild gastrointestinal symptoms. Hyperglycemia, abnormal bleeding, elevations in muscle or liver enzymes, and/or abnormalities in kidney or nerve function have not been reported. Through its intensive purification process, Omacor has minimal "fishy" smell and taste, and it has not been reported to cause hypervitaminosis or illness due to exposure to environmental toxins. Omacor provides a safe, effective, well-tolerated approach to management of hypertriglyceridemia.

Topics: Cholesterol, HDL; Cholesterol, LDL; Clinical Trials as Topic; Docosahexaenoic Acids; Drug Combinations; Drug Therapy, Combination; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Vitamin E

Dyslipidemia including hypercholesterolemia and hypertriglyceridemia often associated with low levels of HDL-cholesterol is a common and important cluster of risk factors for coronary heart disease. Dyslipidemia is also commonly associated with hypertension, hyperinsulinemia and central obesity in the metabolic syndrome. Lifestyle adjustments including increased physical activity and dietary modifications leading to weight reduction are important first steps in the prevention of coronary heart disease in patients with such abnormalities in lipid metabolism. When these adjustments are insufficient to achieve desirable results, the combined treatment with statins and omega-3 fatty acids is an efficient treatment alternative. Both statins and omega-3 fatty acids have documented their effects against coronary heart disease (CHD) both in primary and secondary prevention trials. The mechanisms involved are only partly explained, however, the synergistic effects of statins and omega-3 fatty acids significantly reduce the risk for CHD in patients with dyslipidemia.

Topics: Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Diet; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Exercise; Fatty Acids, Omega-3; Heptanoic Acids; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Hypolipidemic Agents; Pyrroles; Randomized Controlled Trials as Topic; Simvastatin

The purpose of this study was to examine the efficacy and safety of adding ω-3 fatty acids to rosuvastatin in patients with residual hypertriglyceridemia despite statin treatment.. This study was a multicenter, randomized, double-blind, placebo-controlled study. After a 4-week run-in period of rosuvastatin treatment, the patients who had residual hypertriglyceridemia were randomized to receive rosuvastatin 20 mg/d plus ω-3 fatty acids 4 g/d (ROSUMEGA group) or rosuvastatin 20 mg/d (rosuvastatin group) with a 1:1 ratio and were prescribed each medication for 8 weeks.. A total of 201 patients were analyzed (mean [SD] age, 58.1 [10.7] years; 62.7% male). After 8 weeks of treatment, the percentage change from baseline in triglycerides (TGs) and non-HDL-C was significantly greater in the ROSUMEGA group than in the rosuvastatin group (TGs: -26.3% vs -11.4%, P < 0.001; non-HDL-C: -10.7% vs -2.2%, P = 0.001). In the linear regression analysis, the lipid-lowering effect of ω-3 fatty acids was greater when baseline TG or non-HDL-C levels were high and body mass index was low. The incidence of adverse events was not significantly different between the 2 groups.. In patients with residual hypertriglyceridemia despite statin treatment, a combination of ω-3 fatty acids and rosuvastatin produced a greater reduction of TGs and non-HDL-C than rosuvastatin alone. Further study is needed to determine whether the advantages of this lipid profile of ω-3 fatty acids actually leads to the prevention of cardiovascular event. ClinicalTrials.gov identifier: NCT03026933.

Topics: Aged; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Eicosapentaenoic Acid; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Male; Middle Aged; Rosuvastatin Calcium; Treatment Outcome

The US Food and Drug Administration has approved several highly purified ω-3 fatty acid prescription drugs for the treatment of severe hypertriglyceridemia. These differ in the amounts and forms of docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA). This study compared the bioavailability of SC401 (1530 mg EPA-ethyl esters [EEs] and DHA-EEs plus Advanced Lipid Technologies. This was a Phase I, randomized, open-label, single-dose, 2-way crossover study in healthy participants housed from day -3 to day 2 in each treatment period. Blood samples for pharmacokinetic measurements were collected before and after dosing, and safety profile and tolerability were assessed.. In unadjusted analyses, SC401 had 5% lower C. These results indicate that SC401, an ω-3 acid EE formulation containing ALT

Topics: Adult; Biological Availability; Chemistry, Pharmaceutical; Cross-Over Studies; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Male; Middle Aged; Young Adult

Low-density lipoproteins (LDLs) comprise a heterogeneous group of particles with various size and density. A shift to larger LDL particle size is mainly the result of a decrease in small dense LDL (sd-LDL) levels and an increase in large buoyant LDL (lb-LDL) levels.. In a randomized, double-blind study of TAK-085 (containing docosahexaenoic and eicosapentaenoic acid-ethyl esters [EPA-E]) and an EPA-E product in Japanese patients with hypertriglyceridemia, exploratory evaluations of the effects of the LDL particle size were performed on the basis of LDL-cholesterol/apolipoprotein B ratios and LDL subfractions, which were analyzed with a polyacrylamide gel electrophoresis system.. Patients were randomized to 12-week treatment with TAK-085 4 g/day (N = 210), TAK-085 2 g/day (N = 205), or EPA-E 1.8 g/day (N = 195). Treatment with TAK-085 4 g/day, TAK-085 2 g/day, and EPA-E 1.8 g/day caused an increase in the LDL cholesterol/apolipoprotein B ratios (3.99%, 3.35%, and 0.66%, respectively), the mean diameter of LDL particles (1.12%, 0.84%, and 0.67%, respectively), and the level of lb-LDL at the end of the study (16.37%, 9.51%, and 7.31%, respectively). The increases in the LDL cholesterol/apolipoprotein B ratios and the mean diameter of LDL particles from baseline to the end of the study were greater with TAK-085 4 g/day than EPA-E 1.8 g/day. TAK-085 4 g/day and TAK-085 2 g/day caused a decrease in the sd-LDL levels (-16.21% and -6.96%, respectively).. TAK-085 produced a favorable shift in the LDL particle size in Japanese patients with hypertriglyceridemia. JAPIC Clinical Trials Information: Japic CTI-090937.

Topics: Adult; Aged; Apolipoprotein B-100; Biomarkers; Cholesterol, LDL; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Female; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Japan; Male; Middle Aged; Particle Size; Time Factors; Treatment Outcome

This study examined the dose-dependent effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation on heart rate variability (HRV) at rest and during standard laboratory stress tasks. We also investigated whether EPA + DHA supplementation was associated with changes in mood state.. This placebo-controlled, double-blind, randomized, three-period crossover trial (8-week treatment, 6-week washout) compared two doses of EPA + DHA supplementation (0.85 and 3.4 g/d) in 26 adults with elevated triglycerides. After each treatment period, HRV was assessed during an acute stress protocol that included a resting baseline, standard laboratory stress tasks (speech task and cold pressor), and recovery periods. In addition, mood state was assessed.. Root mean square of successive differences in interbeat interval and total power increased 9.9% and 20.6%, respectively, after the high dose relative to placebo (Tukey p = .016 and .012, respectively). The low dose was not significantly different from the high dose or placebo dose. There was a trend for a treatment effect on high-frequency HRV (p = .058), with 21.0% greater power observed after the high dose compared with placebo (Tukey p = .052). Mood did not differ between treatments, and there was no association between mood state and HRV.. In healthy adults with elevated triglycerides, supplementation of 3.4 g/d EPA + DHA resulted in greater HRV, whereas 0.85 g/d EPA + DHA had no effect. These results indicate that EPA + DHA supplementation may improve autonomic tone in adults at increased risk for cardiovascular disease within 8 weeks.. NCT00504309 (ClinicalTrials.gov).

Topics: Anxiety; Cold Temperature; Cross-Over Studies; Depression; Dietary Supplements; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Electrocardiography; Exercise Test; Fatty Acids, Omega-3; Heart Rate; Humans; Hypertriglyceridemia; Rest; Speech; Stress, Physiological; Stress, Psychological

Prescription omega-3-acid ethyl esters (PO-3A) have been tested for outcome benefits in patients with coronary artery disease (CAD), arrhythmias and heart failure. Some evidence suggests that PO-3A may exert their benefit via inhibiting platelets. We tested the hypothesis that PO-3A may inhibit platelet activity in patients with documented stable CAD, beyond the antiplatelet properties of aspirin and statins.. Thirty patients with documented CAD and triglycerides over 250 mg/dl treated with aspirin (70-160 mg/daily) and statins (simvastatin equivalence dose: 5-40 mg/daily) were randomized 1:1:1 to Omacor™ 1 g/day (DHA/EPA ratio 1.25:1.0), Omacor 2 g/day, or a placebo for 2 weeks. Platelet tests including aggregometry and flow cytometry and cartridge analyzer readings were performed at baseline and at 1 and 2 weeks following PO-3A therapy.. ADP-induced platelet aggregation (p = 0.037), GP IIb/IIIa antigen (p = 0.031) and activity (p = 0.024), and P-selectin (p = 0.041) were significantly reduced after PO-3A, while platelet/endothelial cell adhesion molecule (p = 0.09), vitronectin receptor (p = 0.16), formation of platelet-monocyte microparticles (p = 0.19) and the VerifyNow IIb/IIIa test (p = 0.27) only exhibited nonsignificant trends suggestive of reduced platelet activity. Finally, collagen- and arachidonic acid-induced aggregation, closure time with the PFA-100 device and expression of thrombospondin (CD36), GP Ib (CD42b), LAMP-3 (CD63), LAMP-1 (CD107a), CD40-ligand (CD154), GP37 (CD165), and PAR-1 receptor intact (SPAN 12) and cleaved (WEDE-15) epitopes were not affected by 2 weeks of PO-3A.. Independently of the dose and already at 1 week, short-term therapy with PO-3A provided a modest reduction of platelet activity biomarkers, despite concomitant aspirin and statin therapy, when compared to a placebo. The effect of PO-3A is unique, differs from other known antiplatelet agents and suggests potential pleiotropism. These preliminary randomized data call for confirmation in prospective studies.

Topics: Aged; Biomarkers; Coronary Artery Disease; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Humans; Hypertriglyceridemia; Male; Middle Aged; Platelet Activation; Platelet Function Tests; Platelet Membrane Glycoproteins

To evaluate the effects of prescription omega-3-acid ethyl esters on non-high-density lipoprotein cholesterol (HDL-C) levels in atorvastatin-treated patients with elevated non-HDL-C and triglyceride levels.. This study, conducted between February 15, 2007, and October 22, 2007, randomized patients with elevated non-HDL-C (>160 mg/dL) and triglyceride (>or=250 mg/dL and

Topics: Analysis of Variance; Atorvastatin; Cholesterol, HDL; Cholesterol, LDL; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Double-Blind Method; Drug Combinations; Drug Prescriptions; Drug Therapy, Combination; Eicosapentaenoic Acid; Female; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertriglyceridemia; Male; Middle Aged; Pyrroles; Treatment Outcome; United States

Patients with elevated serum triglyceride (TG) levels often have elevations in non-high-density lipoprotein cholesterol (non-HDL-C) levels as well. The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) has identified non-HDL-C as a secondary therapeutic target in these patients, but treatment goals may not be reached with statin monotherapy alone.. This study evaluated the effects on non-HDL-C and other variables of adding prescription omega-3-acid ethyl esters (P-OM3; Lovaza, formerly Omacor [Reliant Pharmaceuticals, Inc., Liberty Corner, New Jersey]) to stable statin therapy in patients with persistent hypertriglyceridemia.. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in adults who had received > or = 8 weeks of stable statin therapy and had mean fasting TG levels > or = 200 and < 500 mg/dL and mean low-density lipoprotein cholesterol levels < or = 10% above their NCEP ATP III goal. The study regimen consisted of an initial 8 weeks of open-label simvastatin 40 mg/d and dietary counseling, followed by 8 weeks of randomized treatment with double-blind P-OM3 4 g/d plus simvastatin 40 mg/d or placebo plus simvastatin 40 mg/d. The main outcome measure was the percent change in non-HDL-C from baseline to the end of treatment.. The evaluable population included 254 patients, of whom 57.5% (146) were male and 95.7% (243) were white. The mean (SD) age of the population was 59.8 (10.4) years, and the mean weight was 92.0 (19.6) kg. At the end of treatment, the median percent change in non-HDL-C was significantly greater with P-OM3 plus simvastatin compared with placebo plus simvastatin (-9.0% vs -2.2%, respectively; P < 0.001). P-OM3 plus simvastatin was associated with significant reductions in TG (29.5% vs 6.3%) and very-low-density lipoprotein cholesterol (27.5% vs 7.2%), a significant increase in high-density lipoprotein cholesterol (HDL-C) (3.4% vs -1.2%), and a significant reduction in the total cholesterol:HDL-C ratio (9.6% vs 0.7%) (all, P < 0.001 vs placebo). Adverse events (AEs) reported by > or= 1% of patients in the P-OM3 group that occurred with a higher frequency than in the group that received simvastatin alone were nasopharyngitis (4 [3.3%]), upper respiratory tract infection (4 [3.3%]), diarrhea (3 [2.5%]), and dyspepsia (3 [2.5%]). There was no significant difference in the frequency of AEs between groups. No serious AEs were considered treatment related.. In these adult, mainly white patients with persistent hypertriglyceridemia, P-OM3 plus simvastatin and dietary counseling improved non-HDL-C and other lipid and lipoprotein parameters to a greater extent than simvastatin alone.

Topics: Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Eicosapentaenoic Acid; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Male; Middle Aged; Simvastatin

Omega-3 fatty acids, such as those present in fish oil, have been reported to prolong life in myocardial infarction survivors. These fatty acids can decrease serum triglyceride concentrations, but so far the doses used in trials examining their effects on coronary end points have had only minimal triglyceride lowering effects.. To examine the triglyceride lowering effectiveness, safety, and tolerability of Omacor, a concentrate of omega-3, long chain, polyunsaturated fatty acids from fish oil (84% of the total as opposed to an average of 35% in fish oil) over one year in patients with established coronary heart disease (CHD) and persisting hypertriglyceridaemia, despite receiving simvastatin in doses similar to those employed in the Scandinavian simvastatin survival study.. 59 patients with CHD, receiving simvastatin 10-40 mg daily with serum triglycerides > 2.3 mmol/l, were randomised to receive Omacor 2 g twice a day or placebo for 24 weeks in a double blind trial. Forty six patients accepted the offer of active treatment for a further 24 weeks in an open phase of the trial.. There was a sustained significant decrease in serum triglycerides by 20-30% (p < 0.005) and in very low density lipoprotein (VLDL) cholesterol by 30-40% (p < 0.005) in patients receiving active Omacor at three, six, and 12 months compared either to baseline or placebo. Omacor did not have any deleterious effect on low density or high density lipoprotein cholesterol or on biochemical and haematological safety tests. There was no adverse effect on glycaemic control in patients with diabetes, who showed a decrease in serum triglyceride, which was at least as great as in non-diabetic patients. One patient receiving placebo died of acute myocardial infarction. Three patients withdrew from the trial (two on placebo and one on active treatment). Omacor was generally well tolerated.. Omacor was found to be a safe and effective means of lowering serum triglycerides over one year in patients with CHD and combined hyperlipidaemia, whose triglycerides remained elevated despite simvastatin treatment.

Topics: Adult; Aged; Cholesterol; Coronary Disease; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Eicosapentaenoic Acid; Female; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Lipoproteins; Male; Middle Aged; Simvastatin; Triglycerides

The objective of this open-label, preliminary study was to assess the efficacy of omega-3 fatty acids for treating dyslipidemia associated with use of atypical antipsychotics.. Participants treated with atypical antipsychotics who had hypertriglyceridemia (> 200 mg/dL) and/or hypercholesterolemia (> 250 mg/dL) were enrolled in an open trial and received omega-3 fatty acids (Lovaza) for up to 16 weeks. Serum lipid profiles were re-assessed at 8 and 16 weeks.. Twenty-eight participants with dyslipidemia enrolled in the trial; 16 were evaluable with post-baseline assessments. There was an average decrease in triglyceride levels of 54.13 ± 83.44 mg/dL (P = .04). A more pronounced benefit of omega-3 supplementation was observed in participants with elevated triglyceride levels at baseline (> 200 mg/dL), compared with those with elevated cholesterol values but normal or more modestly elevated triglyceride levels at enrollment. Participants with hypertriglyceridemia at baseline (n = 10, > 200 mg/dL) experienced a mean decrease in triglyceride levels of 75.8 ± 28.71 mg/dL, a significantly larger decrease than was observed among all participants (P = .005).. Omega-3 supplementation reduced triglyceride levels but not levels of total cholesterol. Recruitment and retention in this study was challenging, and could indicate a lack of screening for dyslipidemia among atypical antipsychotic users/prescribers or could reflect the over-the- counter availability of omega-3 fatty acids.

Topics: Adult; Antipsychotic Agents; Cholesterol; Dietary Supplements; Docosahexaenoic Acids; Drug Combinations; Drug Monitoring; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Humans; Hypercholesterolemia; Hypertriglyceridemia; Hypolipidemic Agents; Male; Mental Disorders; Middle Aged; Treatment Outcome; Triglycerides

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

Topics: Dietary Supplements; Docosahexaenoic Acids; Drug Approval; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fish Oils; Humans; Hypertriglyceridemia; Hypolipidemic Agents; United States; United States Food and Drug Administration

Omega-3 fatty acids are important in treatment of severe primary hypertriglyceridemia (HTG). In 15 patients with severe primary HTG (TG >500 mg/dl despite conventional TG lowering therapy), we assessed efficacy-safety of sequential monthly treatment with Lovaza, 4 to 8 to 12 g/day.. With TG >500 mg/dl despite Type V diet, hyperinsulinemia and diabetes control, and fibric acids, Lovaza (4 g/d) was added for 1 month, and if TG remained >500 mg/dl, increased to 8 g/d for 1 month, and then to 12 g/d for 1 month, and subsequently reduced to 4 g/day for 4 months.. Primary HTG, median TG 884 mg/dl, 14 men, 1 woman, all white, age 50 ± 7 years, 12 non-diabetic, 3 with stable diabetes control. Weight and diet held stable throughout. In 5 patients, after 1, 2, and 3 months on 4 g/day, TG fell <500, mean 1390 to 234 (-83%, p<.0001), to 135 (-90%, p<.0001), and 158 mg/dl (-89%, p<.0001), with a negative TG slope, p=.0013. Non-HDLC fell from 320 to 177 (-45%, p=.001), to 152 (-53%, p=.0002), and to 163 (-49%, p=.0004), with a negative slope, p=.01. In 10 patients, with Lovaza increased from 4 to 8 to 12 g, 3 failed to respond. In 7 of these 10 patients, TG fell 37% from 1075 to 672 on 4 g (p=.006), to 577 on 8 g (-46%, p=.0009), and to 428 mg/dl (-60%, p<.0001) on 12 g/day, with a negative TG slope, p=.0018. TG on 12 g/day was lower than on 8 g/day, p =.03. Non-HDLC fell from 245 to 217 mg/dl (-11%) on 4 g/day, to 203 (-17%, p=.01) on 8 g/day, and to 192 (-22%, p=.003) on 12 g/day, with a negative slope, p=.016. Compared to pre-Lovaza baseline, no abnormal measures developed in safety tests. The 4, 8, and 12 g/d Lovaza doses were well tolerated.. Titration of Lovaza from 4 to 8 to 12 g/d safely offers an effective way to lower TG beyond conventional 4 g therapy.

Topics: Aged; Body Weight; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Humans; Hypertriglyceridemia; Hypolipidemic Agents; Male; Middle Aged; Triglycerides

Topics: Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Humans; Hypertriglyceridemia; Life Style; Metabolic Syndrome

Preclinical and clinical studies demonstrate that the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) as a triacylglycerol (TAG) or an ethyl ester are protective against cardiovascular disease. Both have significant TAG-lowering effects. We developed a concentrated ethyl ester of DHA (MATK-90, 900 mg/g) using microalgae as its source. This study evaluated the effects that different doses of MATK-90 had on lipid levels and clinical parameters in male Wistar rats fed a high-fructose diet used to induce hypertriglyceridemia (TAG > or = 300 mg/dL). Effects of MATK-90 were compared to those produced by a pharmaceutical product (Lovaza, formerly Omacor, P-OM3; 465 mg EPA + 375 mg DHA), a TAG oil used in food (DHASCO, algal-DHA, 40% DHA by weight), and a control (corn oil). Doses of MATK-90 (0.6, 1.3, 2.5, 5.0 g kg(-1) day(-1)), algal-DHA (2 g DHA kg(-1) day(-1)), and P-OM3 (5.0 g kg(-1) day(-1)) were administered by oral gavage for 28 days. A significant dose-related decrease was observed in TAG and cholesterol levels in all but the lowest dose of MATK-90 treatment group vs. control. The high-dose group of MATK-90 and the P-OM3 group produced similar reductions in TAG levels.

Topics: Animals; Body Weight; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Diet; Docosahexaenoic Acids; Drug Combinations; Eating; Eicosapentaenoic Acid; Eukaryota; Fatty Acids; Fructose; Hypertriglyceridemia; Hypolipidemic Agents; Lipid Metabolism; Male; Rats; Rats, Wistar; Triglycerides

Topics: Coronary Disease; Drug Therapy, Combination; Fatty Acids, Omega-3; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertriglyceridemia; Hypolipidemic Agents

Topics: Drug Therapy, Combination; Fatty Acids, Omega-3; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypertriglyceridemia; Hypolipidemic Agents

Topics: Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Humans; Hypertriglyceridemia; Triglycerides

Topics: Controlled Clinical Trials as Topic; Coronary Disease; Costs and Cost Analysis; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Dose-Response Relationship, Drug; Drug Combinations; Drug Interactions; Dyspepsia; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia

Topics: Death, Sudden, Cardiac; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatty Acids, Omega-3; Humans; Hypertriglyceridemia; Myocardial Infarction; Secondary Prevention; Survival Rate