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)
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)
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DOI：
10.1016/j.jacl.2012.07.001
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发表时间：
2012-12-01
影响因子：
4.4
通讯作者：
Soni, Paresh N.
中科院分区：
文献类型：
--
作者：
Bays, Harold E.;Braeckman, Rene A.;Soni, Paresh N.
背景：二十碳五烯酸乙酯（Icosapent ethyl，IPE;原名AMR 101）是一种高纯度的二十碳五烯酸乙酯处方药。在MARINE研究中，我们评估了IPE在甘油三酯非常高的患者中的疗效和安全性（TG; >= 500 mg/dL）和先前证明TG水平显著降低，而低密度脂蛋白（LDL）胆固醇水平没有显著增加。结论：在这个后续的探索性分析中，我们报告了IPE对脂蛋白颗粒浓度和大小的影响。MARINE是一项III期、多中心、安慰剂对照、随机、双盲、12周研究。将高胆固醇血症患者（N = 229）随机分为三个治疗组：IPE 4 g/天、IPE 2 g/天或安慰剂。结果：与安慰剂组相比，IPE 4g/天组显著降低了大极低密度脂蛋白的中位浓度（VLDL; -27.9%; P = .0211），总LDL（-16.3%; P = .0006），小LDL（-25.6%; P <0.0001）、总高密度脂蛋白（HDL; -7.4%; P = 0.0063）颗粒和减小的VLDL颗粒大小（-8.6%; P = 0.0017）。在TG >= 500 mg/dL的患者人群中，IPE没有显著改变LDL或HDL颗粒的总体尺寸。结论：IPE 4 g/天显著降低TG >= 500 mg/dL患者中的大VLDL、总LDL、小LDL和总HDL颗粒浓度以及VLDL颗粒尺寸。VLDL颗粒浓度和大小的变化反映了二十碳五烯酸降低TG的作用。在omega-3治疗中，IPE降低LDL颗粒浓度是新的，与先前报道的TG水平极高的患者中IPE降低载脂蛋白B和LDL-C增加不足一致。临床试验注册号：NCT 01047683。(C)2012年国家脂质协会。All rights reserved.
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.