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Hypertriglyceridemia: HELP
Articles from Miscellaneous institutions in Louisville
Based on 14 articles published since 2010
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These are the 14 published articles about Hypertriglyceridemia that originated from Miscellaneous institutions in Louisville during 2010-2020.
 
+ Citations + Abstracts
1 Clinical Trial Effects of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) on Atherogenic Lipid/Lipoprotein, Apolipoprotein, and Inflammatory Parameters in Patients With Elevated High-Sensitivity C-Reactive Protein (from the ANCHOR Study). 2019

Miller, Michael / Ballantyne, Christie M / Bays, Harold E / Granowitz, Craig / Doyle, Ralph T / Juliano, Rebecca A / Philip, Sephy. ·Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland. Electronic address: mmiller@som.umaryland.edu. · Department of Medicine, Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky. · Amarin Pharma Inc, Bedminster, New Jersey. ·Am J Cardiol · Pubmed #31277790.

ABSTRACT: Icosapent ethyl is pure prescription eicosapentaenoic acid approved at 4 g/day as an adjunct to diet to reduce triglycerides (TG) in adults with TG ≥500 mg/dl. Elevated high-sensitivity C-reactive protein (hsCRP) is associated with increased cardiovascular risk. The 12-week ANCHOR study randomized 702 statin-treated patients at increased cardiovascular risk with TG 200 to 499 mg/dl despite low-density lipoprotein cholesterol (LDL-C) control (40 to 99 mg/dl). This post hoc analysis assessed 246 ANCHOR patients with baseline hsCRP ≥ 2.0 mg/L randomized to icosapent ethyl 4 g/day (n = 126; approved dose) or placebo (n = 120). Without increasing LDL-C, icosapent ethyl significantly reduced median TG (-20%; p < 0.0001), non-high-density lipoprotein cholesterol (-12.3%; p < 0.0001), total cholesterol (-11.1%; p < 0.0001), high-density lipoprotein cholesterol (-5.2%; p = 0.0042), very LDL-C (-21.0%; p < 0.0001), very low-density lipoprotein TG (-22.9%; p < 0.0001), remnant lipoprotein cholesterol (-23.0%; p = 0.0125), apolipoprotein B (-7.4%; p = 0.0021), apolipoprotein C-III (-16%; p < 0.0001), oxidized LDL (-13.7%; p = 0.0020), lipoprotein-associated phospholipase A

2 Clinical Trial Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on remnant-like particle cholesterol from the MARINE and ANCHOR studies. 2016

Ballantyne, Christie M / Bays, Harold E / Philip, Sephy / Doyle, Ralph T / Braeckman, Rene A / Stirtan, William G / Soni, Paresh N / Juliano, Rebecca A. ·Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, 6565 Fannin St. MSA 601, Houston, TX 77030, USA. Electronic address: cmb@bcm.tmc.edu. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA. · Amarin Pharma Inc., Bedminster, NJ, USA. ·Atherosclerosis · Pubmed #27596132.

ABSTRACT: BACKGROUND AND AIMS: Remnant-like particle cholesterol (RLP-C) is atherogenic and may increase atherosclerotic cardiovascular disease risk. Icosapent ethyl is a high-purity prescription eicosapentaenoic acid ethyl ester (approved as an adjunct to diet to reduce triglyceride [TG] levels in adult patients with TGs ≥500 mg/dL [≥5.65 mmol/L] at 4 g/day). In the MARINE and ANCHOR studies, icosapent ethyl reduced TG and other atherogenic lipid parameter levels without increasing low-density lipoprotein cholesterol (LDL-C) levels. This exploratory analysis evaluated the effects of icosapent ethyl on calculated and directly measured RLP-C. METHODS: MARINE (TGs ≥500 and ≤2000 mg/dL [≥5.65 mmol/L and ≤22.6 mmol/L]) and ANCHOR (TGs ≥200 and <500 mg/dL [≥2.26 and <5.65 mmol/L] despite statin-controlled LDL-C) were phase 3, 12-week, double-blind studies that randomized adult patients to icosapent ethyl 4 g/day, 2 g/day, or placebo. This analysis assessed median percent change from baseline to study end in directly measured (immunoseparation assay) RLP-C levels (MARINE, n = 218; ANCHOR, n = 252) and calculated RLP-C levels in the full populations. RESULTS: Icosapent ethyl 4 g/day significantly reduced directly measured RLP-C levels -29.8% (p = 0.004) in MARINE and -25.8% (p = 0.0001) in ANCHOR versus placebo, and also reduced directly measured RLP-C levels to a greater extent in subgroups with higher versus lower baseline TG levels, in patients receiving statins versus no statins (MARINE), and in patients receiving medium/higher-intensity versus lower-intensity statins (ANCHOR). Strong correlations were found between calculated and directly measured RLP-C for baseline, end-of-treatment, and percent change values in ANCHOR and MARINE (0.73-0.92; p < 0.0001 for all). CONCLUSIONS: Icosapent ethyl 4 g/day significantly reduced calculated and directly measured RLP-C levels versus placebo in patients with elevated TG levels from the MARINE and ANCHOR studies.

3 Clinical Trial Effects of icosapent ethyl on lipoprotein particle concentration and size in statin-treated patients with persistent high triglycerides (the ANCHOR Study). 2015

Ballantyne, Christie M / Braeckman, Rene A / Bays, Harold E / Kastelein, John J / Otvos, James D / Stirtan, William G / Doyle, Ralph T / Soni, Paresh N / Juliano, Rebecca A. ·Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. Electronic address: cmb@bcm.tmc.edu. · Amarin Pharma Inc., Bedminster, NJ, USA. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA. · Academic Medical Center, Amsterdam, The Netherlands. · LipoScience, Raleigh, NC, USA. ·J Clin Lipidol · Pubmed #26073397.

ABSTRACT: BACKGROUND: Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved at a dose of 4 g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe hypertriglyceridemia (TG ≥ 500 mg/dL). OBJECTIVE: In this prespecified exploratory analysis from the ANCHOR study of patients at high cardiovascular risk with TG ≥ 200 and <500 mg/dL despite statin control of low-density lipoprotein cholesterol, we assessed the effects of IPE on lipoprotein particle concentration and size and examined correlations of atherogenic particles with apolipoprotein B (ApoB). METHODS: Nuclear magnetic resonance spectroscopy was used to measure lipoprotein particle concentration and size. RESULTS: Compared with placebo (n = 211), IPE 4 g/day (n = 216) significantly reduced concentrations of: total (12.2%, P = .0002), large (46.4%, P < .0001), and medium (12.1%, P = .0068) very-low-density lipoprotein (VLDL) particles; total (7.7%, P = .0017) and small (13.5%, P < .0001) LDL particles; and total (7.4%, P < .0001) and large (31.0%, P < .0001) high-density lipoprotein particles. Atherogenic lipoprotein particles (total VLDL and total LDL) correlated with ApoB at baseline (R(2) = 0.57) and week 12 (R(2) = 0.65) as did total LDL particle concentration at baseline (R(2) = 0.53) and week 12 (R(2) = 0.59). Compared with placebo, IPE 4 g/day significantly reduced VLDL (7.7%, P < .0001) and high-density lipoprotein (1.2%, P = .0014) particle sizes with a modest but significant increase in LDL particle size (0.5%, P = .0031). CONCLUSIONS: Compared with placebo, treatment with IPE 4 g/day for 12 weeks reduced key atherogenic lipoprotein particle concentrations. At both baseline and end of study, atherogenic lipoprotein concentrations correlated with ApoB.

4 Clinical Trial Icosapent ethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies. 2013

Bays, Harold E / Ballantyne, Christie M / Braeckman, Rene A / Stirtan, William G / Soni, Paresh N. ·Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA. HBaysMD@aol.com ·Am J Cardiovasc Drugs · Pubmed #23325450.

ABSTRACT: BACKGROUND: Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved by the US Food and Drug Administration as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. In addition to TG-lowering effects, IPE also reduces non-high-density lipoprotein cholesterol and apolipoprotein B levels without significantly increasing low-density lipoprotein cholesterol (LDL-C) in patients with very high TG levels ≥500 mg/dL (MARINE study) and in patients with well-controlled LDL-C and residually high TG levels 200-500 mg/dL (ANCHOR study). This analysis examined the effect of IPE on inflammatory markers in patients from MARINE and ANCHOR. METHODS: MARINE (N = 229) and ANCHOR (N = 702) were Phase III, double-blind studies that randomized hypertriglyceridemic patients to IPE 4 g/day, 2 g/day, or placebo. This analysis assessed the median placebo-adjusted percentage change from baseline in markers representing various stages of atherosclerotic inflammation such as intercellular adhesion molecule-1 (ICAM-1), oxidized low-density lipoprotein (Ox-LDL), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP). RESULTS: Compared to placebo, IPE 4 g/day significantly decreased Ox-LDL (13 %, p < 0.0001, ANCHOR), Lp-PLA(2) (14 %, p < 0.001, MARINE; 19 %, p < 0.0001, ANCHOR), and hsCRP levels (36 %, p < 0.01, MARINE; 22 %, p < 0.001, ANCHOR), but did not significantly change ICAM-1 and IL-6 levels. In the MARINE study, IPE 2 g/day did not significantly change ICAM-1, Ox-LDL, Lp-PLA(2), IL-6, or hsCRP levels. Also, compared to placebo in the ANCHOR study, IPE 2 g/day significantly decreased Lp-PLA(2) levels (8 %, p < 0.0001), but did not significantly change levels of other assessed inflammatory markers. CONCLUSION: Compared to placebo, in hypertriglyceridemic patients, IPE 4 g/day significantly decreased Ox-LDL, Lp-PLA(2), and hsCRP levels.

5 Clinical Trial Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study). 2012

Bays, Harold E / Braeckman, Rene A / Ballantyne, Christie M / Kastelein, John J / Otvos, James D / Stirtan, William G / Soni, Paresh N. ·Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA. hbaysmd@aol.com ·J Clin Lipidol · Pubmed #23312052.

ABSTRACT: BACKGROUND: Icosapent ethyl (IPE; formerly AMR101) is a high-purity prescription form of eicosapentaenoic acid ethyl ester. In the MARINE study we evaluated the efficacy and safety of IPE in patients with very high triglycerides (TG; ≥500 mg/dL) and previously demonstrated significant reductions in TG levels with no significant increases in low-density lipoprotein (LDL) cholesterol levels. OBJECTIVES: In this follow-up, exploratory analysis, we report the effects of IPE on lipoprotein particle concentration and size. METHODS: MARINE was a phase 3, multicenter, placebo-controlled, randomized, double-blind, 12-week study. Hypertriglyceridemic patients (N = 229) were randomized to three treatment groups: IPE 4 g/day, IPE 2 g/day, or placebo. Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy. RESULTS: Compared with placebo, IPE 4 g/day significantly reduced median concentrations of large very-low-density lipoprotein (VLDL; -27.9%; P = .0211), total LDL (-16.3%; P = .0006), small LDL (-25.6%; P < .0001), and total high-density lipoprotein (HDL; -7.4%; P = .0063) particles and reduced VLDL particle size (-8.6%; P = .0017). In this patient population with TG ≥500 mg/dL, IPE did not significantly change the overall sizes of LDL or HDL particles. CONCLUSION: IPE 4 g/day significantly reduced large VLDL, total LDL, small LDL, and total HDL particle concentrations and VLDL particle size in patients with TG ≥500 mg/dL. Changes in VLDL particle concentration and size reflect the TG-lowering effects of eicosapentaenoic acid. The reduction in LDL particle concentration with IPE is novel among ω-3 therapies and is consistent with the previously reported reduction in apolipoprotein B and lack of LDL-C increase with IPE in patients with very high TG levels. CLINICAL TRIAL REGISTRATION NUMBER: NCT01047683.

6 Clinical Trial Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). 2011

Bays, Harold E / Ballantyne, Christie M / Kastelein, John J / Isaacsohn, Jonathan L / Braeckman, Rene A / Soni, Paresh N. ·Louisville Metabolic and Atherosclerosis Research Center, Kentucky, USA. hbaysmd@aol.com ·Am J Cardiol · Pubmed #21683321.

ABSTRACT: AMR101 is an omega-3 fatty acid agent containing ≥96% eicosapentaenoic acid ethyl ester and no docosahexaenoic acid. Previous smaller studies suggested that highly purified eicosapentaenoic acid lowered triglyceride (TG) levels without increasing low-density lipoprotein (LDL) cholesterol levels. TG-lowering therapies such as fibrates, and fish oils containing both eicosapentaenoic acid and docosahexaenoic acid, can substantially increase LDL cholesterol levels when administered to patients with very high TG levels (≥500 mg/dl). The present double-blind study randomized 229 diet-stable patients with fasting TG ≥500 mg/dl and ≤2,000 mg/dl (with or without background statin therapy) to AMR101 4 g/day, AMR101 2 g/day, or placebo. The primary end point was the placebo-corrected median percentage of change in TG from baseline to week 12. The baseline TG level was 680, 657, and 703 mg/dl for AMR101 4 g/day, AMR101 2 g/day, and placebo. AMR101 4 g/day reduced the placebo-corrected TG levels by 33.1% (n = 76, p <0.0001) and AMR101 2 g/day by 19.7% (n = 73, p = 0.0051). For a baseline TG level >750 mg/dl, AMR101 4 g/day reduced the placebo-corrected TG levels by 45.4% (n = 28, p = 0.0001) and AMR101 2 g/day by 32.9% (n = 28, p = 0.0016). AMR101 did not significantly increase the placebo-corrected median LDL cholesterol levels at 4 g/day (-2.3%) or 2 g/day (+5.2%; both p = NS). AMR101 significantly reduced non-high-density lipoprotein cholesterol, apolipoprotein B, lipoprotein-associated phospholipase A(2), very low-density lipoprotein cholesterol, and total cholesterol. AMR101 was generally well tolerated, with a safety profile similar to that of the placebo. In conclusion, the present randomized, double-blind trial of patients with very high TG levels demonstrated that AMR101 significantly reduced the TG levels and improved other lipid parameters without significantly increasing the LDL cholesterol levels.

7 Article Icosapent ethyl reduces atherogenic markers in high-risk statin-treated patients with stage 3 chronic kidney disease and high triglycerides. 2019

Vijayaraghavan, Krishnaswami / Szerlip, Harold M / Ballantyne, Christie M / Bays, Harold E / Philip, Sephy / Doyle, Ralph T / Juliano, Rebecca A / Granowitz, Craig. ·a Institute of Congestive Heart Failure, Abrazo Arizona Heart Hospital , Phoenix , AZ , USA. · b Nephrology Division and Nephrology Fellowship Program, Baylor University Medical Center , Dallas , TX , USA. · c Department of Medicine, Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center , Houston , TX , USA. · d Louisville Metabolic and Atherosclerosis Research Center , Louisville , KY , USA. · e Medical Affairs, Amarin Pharma Inc ., Bedminster , NJ , USA. · f Clinical Development, Amarin Pharma Inc ., Bedminster , NJ , USA. ·Postgrad Med · Pubmed #31306043.

ABSTRACT:

8 Article Icosapent Ethyl Effects on Fatty Acid Profiles in Statin-Treated Patients With High Triglycerides: The Randomized, Placebo-controlled ANCHOR Study. 2019

Ballantyne, Christie M / Manku, Mehar S / Bays, Harold E / Philip, Sephy / Granowitz, Craig / Doyle, Ralph T / Juliano, Rebecca A. ·Department of Medicine, Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. cmb@bcm.tmc.edu. · Amarin Pharma Inc, Bedminster, NJ, USA. · Clinical Research, Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA. · Medical Affairs, Amarin Pharma Inc, Bedminster, NJ, USA. · Research and Development, Amarin Pharma Inc, Bedminster, NJ, USA. ·Cardiol Ther · Pubmed #30788718.

ABSTRACT: INTRODUCTION: Fatty acid content in plasma and red blood cells (RBCs) may provide insight into potential physiologic benefits of omega-3 fatty acids. Icosapent ethyl is a pure prescription form of eicosapentaenoic acid (EPA) ethyl ester approved by the US Food and Drug Administration at a dose of 4 g/day as an adjunct to diet to reduce triglyceride levels in adults with severe (≥ 500 mg/dl) hypertriglyceridemia. METHODS: This was a prespecified exploratory subset analysis of the ANCHOR study, which randomized 702 statin-treated patients at increased cardiovascular risk with triglycerides 200-499 mg/dl and controlled low-density lipoprotein cholesterol (40-99 mg/dl). This analysis examined effects of icosapent ethyl 4 g/day versus placebo on fatty acid levels in plasma and RBCs using a gas chromatograph assay method with flame ionization detector. RESULTS: In plasma, treatment with icosapent ethyl 4 g/day resulted in significant increases versus placebo in the mean concentrations of EPA (+ 635%; P < 0.0001) and its metabolite, docosapentaenoic acid n-3 (+ 143%; P < 0.0001) with no significant change in docosahexaenoic acid. Treatment with icosapent ethyl 4 g/day versus placebo also resulted in significant decreases in the omega-6 fatty acids linoleic acid (- 25%) and arachidonic acid (AA; - 31%), as well as the AA/EPA ratio (- 91%). Icosapent ethyl 4 g/day also decreased the omega-9 fatty acid oleic acid (- 29%) and the saturated fatty acids palmitic acid (- 23%) and stearic acid (- 16%) (all P < 0.0001). Results were similar for RBCs. CONCLUSIONS: Icosapent ethyl 4 g/day significantly increased EPA and produced other potentially beneficial shifts in fatty acids in plasma and RBCs versus placebo. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, NCT01047501 FUNDING: Amarin Pharma Inc. Plain language summary available for this article.

9 Article Usefulness of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) in Women to Lower Triglyceride Levels (Results from the MARINE and ANCHOR Trials). 2017

Mosca, Lori / Ballantyne, Christie M / Bays, Harold E / Guyton, John R / Philip, Sephy / Doyle, Ralph T / Juliano, Rebecca A. ·Columbia University Medical Center, New York, New York. Electronic address: ljm10@columbia.edu. · Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, Kentucky. · Duke University School of Medicine, Durham, North Carolina. · Amarin Pharma Inc., Bedminster, New Jersey. ·Am J Cardiol · Pubmed #27939227.

ABSTRACT: There are limited data on the efficacy and safety of triglyceride (TG)-lowering agents in women. We conducted subgroup analyses of the effects of icosapent ethyl (a high-purity prescription form of the ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid) on TG levels (primary efficacy variable) and other atherogenic and inflammatory parameters in a total of 215 women with a broad range of TG levels (200-2000 mg/dl) enrolled in two 12-week placebo-controlled trials: MARINE (n = 18; placebo, n = 18) and ANCHOR (n = 91; placebo, n = 88). Icosapent ethyl 4 g/day significantly reduced TG levels from baseline to week 12 versus placebo in both MARINE (-22.7%; p = 0.0327) and ANCHOR (-21.5%; p <0.0001) without increasing low-density lipoprotein cholesterol levels. Significant improvements were also observed in non-high-density lipoprotein cholesterol levels in MARINE (-15.7%; p = 0.0082) and ANCHOR (-14.2%; p <0.0001) and total cholesterol levels in MARINE (-14.9%; p = 0.0023) and ANCHOR (-12.1%; p <0.0001), along with significant increases of >500% in eicosapentaenoic acid levels in plasma and red blood cells (all p <0.001). Icosapent ethyl was well tolerated, with adverse-event profiles comparable with findings in the overall studies. In conclusion, icosapent ethyl 4 g/day significantly reduced TG levels and other atherogenic parameters in women without increasing low-density lipoprotein cholesterol levels compared with placebo; the clinical implications of these findings are being evaluated in the REDUCtion of Cardiovascular Events With Eicosapentaenoic Acid [EPA]-Intervention Trial (REDUCE-IT) cardiovascular outcomes study.

10 Article Icosapent ethyl: Eicosapentaenoic acid concentration and triglyceride-lowering effects across clinical studies. 2016

Bays, Harold E / Ballantyne, Christie M / Doyle, Ralph T / Juliano, Rebecca A / Philip, Sephy. ·Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA. Electronic address: hbaysmd@aol.com. · Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, 6565 Fannin, M.S. A-601, Houston, TX 77030, USA. Electronic address: cmb@bcm.tmc.edu. · Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ 07921, USA. Electronic address: ralph.doyle@amarincorp.com. · Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ 07921, USA. Electronic address: rebecca.juliano@amarincorp.com. · Amarin Pharma Inc., 1430 Route 206, Suite 200, Bedminster, NJ 07921, USA. Electronic address: sephy.philip@amarincorp.com. ·Prostaglandins Other Lipid Mediat · Pubmed #27418543.

ABSTRACT: Icosapent ethyl is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved at a dose of 4g/day as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500mg/dL) hypertriglyceridemia. This post-hoc exploratory analysis examined the relationship of icosapent ethyl dose with EPA concentrations in plasma and red blood cells (RBCs) across 3 clinical studies-a phase 1 pharmacokinetic study in healthy adult volunteers and 2 pivotal phase 3 studies (MARINE and ANCHOR) in adult patients with hypertriglyceridemia-and examined the relationship between EPA levels and TG-lowering effects in MARINE and ANCHOR. In all 3 studies, icosapent ethyl produced dose-dependent increases in the concentrations of EPA in plasma and RBCs. In both MARINE and ANCHOR, these dose-dependent EPA increases correlated with the degree of TG level lowering (all P<0.01). In patients with high TG levels (≥200mg/dL) and treated with icosapent ethyl 4g/day, the end-of-treatment plasma and RBC EPA concentrations were >170μg/mL and>70μg/mL, respectively. These studies support icosapent ethyl as producing predictable dose-dependent pharmacokinetics/pharmacodynamics, with TG level lowering dependent upon icosapent ethyl dose and EPA concentrations in plasma and RBCs.

11 Article Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on plasma apolipoprotein C-III levels in patients from the MARINE and ANCHOR studies. 2016

Ballantyne, Christie M / Bays, Harold E / Braeckman, Rene A / Philip, Sephy / Stirtan, William G / Doyle, Ralph T / Soni, Paresh N / Juliano, Rebecca A. ·Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, Houston, TX, USA. Electronic address: cmb@bcm.tmc.edu. · Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA. · Doylestown, PA, USA. · Amarin Pharma Inc., Bedminster, NJ, USA. · East Lyme, CT, USA. · Mystic, CT, USA. ·J Clin Lipidol · Pubmed #27206952.

ABSTRACT: BACKGROUND: Apolipoprotein C-III (ApoC-III) regulates lipoprotein and triglyceride (TG) metabolism and may have a causal role in cardiovascular disease. In the Multi-Center, Placebo-Controlled, Randomized, Double-Blind, 12-Week Study With an Open-Label Extension (MARINE) and ANCHOR studies, icosapent ethyl, a high-purity prescription eicosapentaenoic acid ethyl ester, reduced TG, and other atherogenic lipid parameters without increasing low-density lipoprotein cholesterol (LDL-C) compared with placebo. OBJECTIVE: To evaluate the effects of icosapent ethyl on plasma ApoC-III levels in patients from 2 phase 3 studies. METHODS: MARINE and ANCHOR were 12-week double-blind studies of icosapent ethyl in adult patients. Patients in MARINE had very high TG levels (≥500 and ≤2000 mg/dL) and patients in ANCHOR had high TG levels (≥200 and <500 mg/dL) despite statin control of LDL-C. This post hoc analysis of MARINE and ANCHOR assessed the median percent change from baseline in plasma ApoC-III levels vs placebo and includes subgroup analyses by statin use/efficacy and median ApoC-III levels. RESULTS: We assessed ApoC-III levels in 148 and 612 patients in the MARINE and ANCHOR studies, respectively. In MARINE, the approved prescription dose of icosapent ethyl (4 g/day) significantly reduced ApoC-III levels by 25.1% (P < .0001) vs placebo. In ANCHOR, icosapent ethyl 4 g/day significantly reduced ApoC-III levels by 19.2% (P < .0001) vs placebo; subanalysis by statin efficacy revealed significant reductions vs placebo in the higher-efficacy and medium-efficacy groups (24.6% and 17.2%, respectively; both P < .0001). CONCLUSION: Icosapent ethyl 4 g/day significantly reduced plasma ApoC-III levels in patients with elevated TGs from the MARINE and ANCHOR studies.

12 Article Icosabutate for the treatment of very high triglycerides: A placebo-controlled, randomized, double-blind, 12-week clinical trial. 2016

Bays, Harold E / Hallén, Jonas / Vige, Runar / Fraser, David / Zhou, Rong / Hustvedt, Svein Olaf / Orloff, David G / Kastelein, John J P. ·L-MARC Research Center, Louisville, KY, USA. · Pronova BioPharma, Lysaker, Norway. · Medpace, Inc, Cincinatti, OH, USA. · Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. Electronic address: j.j.kastelein@amc.uva.nl. ·J Clin Lipidol · Pubmed #26892135.

ABSTRACT: BACKGROUND: Icosabutate is a structurally enhanced omega-3 fatty acid molecule developed with the aim of achieving improved triglyceride (TG)-lowering efficacy, increased potency, and preserved safety compared with conventional prescription omega-3 fatty acid. OBJECTIVE: To evaluate the efficacy and safety of icosabutate 600 mg once daily in patients with very high TGs. METHODS: After a 6-8 week run-in period, men and women with TG levels ≥ 500 mg/dL and ≤ 1500 mg/dL were randomized to double-blind treatment with placebo or icosabutate 600 mg for 12 weeks. The primary end point was % change from baseline in TGs at 12 weeks. RESULTS: A total of 87 subjects were randomized. At baseline, median TG (interquartile range) levels were 611 (543-878) and 688 (596-892) mg/dL, and the median change after 12 weeks of treatment was -51% and -17%, respectively, for a placebo-corrected change of -33% (P < .001). Adjusted for placebo, icosabutate significantly reduced very low-density lipoprotein cholesterol (-36%, P < .001), remnant lipoprotein cholesterol (-34%, P < .001), apolipoprotein (Apo) C-III (-35%, P < .001), trended toward reduced non-high-density lipoprotein cholesterol (-7%, P = .064); significantly increased high-density lipoprotein cholesterol (18%, P < .001) and low-density lipoprotein cholesterol (28%, P < .001), with a trend of an increased lipoprotein (a; 10%, P = .054). No changes were observed in total cholesterol, apolipoprotein B, or apolipoprotein A1. Fasting plasma glucose was unchanged, whereas fasting plasma insulin was reduced (P = .001) with icosabutate. Icosabutate was generally well tolerated. CONCLUSION: Treatment with icosabutate once daily significantly reduced TG, very low-density lipoprotein cholesterol, and Apo C-III levels in patients with very high TG levels. This trial was registered at www.clinicaltrials.gov as NCT01893515.

13 Article Long-term up to 24-month efficacy and safety of concomitant prescription omega-3-acid ethyl esters and simvastatin in hypertriglyceridemic patients. 2010

Bays, Harold E / Maki, Kevin C / McKenney, James / Snipes, Rose / Meadowcroft, Amy / Schroyer, Rosemary / Doyle, Ralph T / Stein, Evan. ·Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA. HBaysMD@aol.com ·Curr Med Res Opin · Pubmed #20156032.

ABSTRACT: OBJECTIVE: Assess the long-term efficacy and safety of prescription omega-3-acid ethyl esters (P-OM3) coadministered with simvastatin in an extension of the Combination of Prescription Omega-3 Plus Simvastatin (COMBOS) trial. METHODS: COMBOS included hypertriglyceridemic patients (triglyceride [TG] >or=200 mg/dL and <500 mg/dL or >or=2.26 mmol/L and <5.64 mmol/L) with low density lipoprotein cholesterol (LDL-C) level no greater than 10% above the National Cholesterol Education Program, Adult Treatment Panel III treatment goal. After an 8-week lead-in phase with simvastatin 40 mg/day (which continued throughout the trial), subjects were randomized to 8 weeks of P-OM3 4 g/day or placebo. Completers were eligible to participate in a 24-month extension study. Those who received placebo + simvastatin in COMBOS switched to open-label P-OM3 + simvastatin ('Switchers'); those who received P-OM3 + simvastatin during COMBOS continued the same regimen (open-label) in the extension phase ('Non-switchers'). The primary endpoint was the difference between Non-switchers and Switchers in median percent change in non-high-density lipoprotein-cholesterol (non-HDL-C) from COMBOS end of treatment to Month 4 of the extension phase. RESULTS: At Month 4 from COMBOS end of treatment, non-HDL-C was reduced by a median of 9.4% in Switchers and increased by 0.9% in Non-switchers (p < 0.001). For the total population (combined Non-switcher + Switcher population), the median percent change from COMBOS baseline to Months 4, 12, and 24 was -8.3%, -7.3%, and -8.9%, respectively (all p < 0.001). This extension study revealed no unexpected safety findings. A limitation of this study was a gap between completion of COMBOS and enrollment in the extension phase for some patients; however, a post-hoc non-HDL-C sensitivity analysis performed at the 4-month primary endpoint revealed no influence of gap on study results. CONCLUSIONS: In this 24-month extension study, P-OM3 was generally well tolerated, and produced sustained reductions in non-HDL-C levels in simvastatin-treated patients with TG levels between 200 and 500 mg/dL (2.26 mmol/L and 5.64 mmol/L). CLINICAL TRIAL REGISTRY NUMBER: NCT00903409.

14 Article Effects of prescription omega-3-acid ethyl esters on non--high-density lipoprotein cholesterol when coadministered with escalating doses of atorvastatin. 2010

Bays, Harold E / McKenney, James / Maki, Kevin C / Doyle, Ralph T / Carter, Roderick N / Stein, Evan. ·Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Ave, Louisville, KY 40213, USA. hbaysmd@aol.com ·Mayo Clin Proc · Pubmed #20118387.

ABSTRACT: OBJECTIVE: 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. PATIENTS AND METHODS: 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 Prescription omega-3-acid ethyl esters plus atorvastatin produced significant improvements in non-HDL-C and other lipid parameters in patients with elevated non-HDL-C and triglyceride levels.