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)

被引:69
作者
Bays, Harold E. [1 ]
Braeckman, Rene A. [2 ]
Ballantyne, Christie M. [3 ,4 ]
Kastelein, John J. [5 ]
Otvos, James D. [6 ]
Stirtan, William G. [2 ]
Soni, Paresh N. [2 ]
机构
[1] Louisville Metab & Atherosclerosis Res Ctr, Louisville, KY 40213 USA
[2] Amarin Pharma Inc, Bedminster, NJ USA
[3] Baylor Coll Med, Houston, TX 77030 USA
[4] Methodist DeBakey Heart & Vasc Ctr, Houston, TX USA
[5] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands
[6] LipoScience, Raleigh, NC USA
关键词
Apolipoprotein B; Eicosapentaenoic acid; High-density lipoproteins; Hypertriglyceridemia; Intermediate-density lipoproteins; Low-density lipoproteins; Triglycerides; Very-low-density lipoproteins; EICOSAPENTAENOIC ACID; CARDIOVASCULAR-DISEASE; DOCOSAHEXAENOIC ACID; DOUBLE-BLIND; LDL; LIPIDS; RISK; MULTICENTER; CHOLESTEROL; FENOFIBRATE;
D O I
10.1016/j.jacl.2012.07.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 omega-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. (C) 2012 National Lipid Association. All rights reserved.
引用
收藏
页码:565 / 572
页数:8
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