Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA.
J Clin Lipidol. 2012 Nov-Dec;6(6):565-72. doi: 10.1016/j.jacl.2012.07.001. Epub 2012 Jul 24.
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.
In this follow-up, exploratory analysis, we report the effects of IPE on lipoprotein particle concentration and size.
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.
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.
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.
NCT01047683.
依泽替米贝（IPE；前身为 AMR101）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（TG；≥500mg/dL）极高的患者中的疗效和安全性，并证实其可显著降低 TG 水平，同时不会显著增加低密度脂蛋白（LDL）胆固醇水平。
在本次后续、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 是一项为期 12 周的、多中心、安慰剂对照、随机、双盲、3 组的 3 期临床试验。将高甘油三酯血症患者（N=229）随机分为三组：IPE 4g/天组、IPE 2g/天组或安慰剂组。采用核磁共振光谱法检测脂蛋白颗粒浓度和大小。
与安慰剂相比，IPE 4g/天组可显著降低大 VLDL（-27.9%；P=0.0211）、总 LDL（-16.3%；P=0.0006）、小 LDL（-25.6%；P<0.0001）和总 HDL（-7.4%；P=0.0063）颗粒的中位数浓度，并降低 VLDL 颗粒大小（-8.6%；P=0.0017）。在 TG≥500mg/dL 的患者人群中，IPE 对 LDL 或 HDL 颗粒的总体大小没有显著影响。
IPE 4g/天可显著降低 TG≥500mg/dL 患者的大 VLDL、总 LDL、小 LDL 和总 HDL 颗粒浓度以及 VLDL 颗粒大小。VLDL 颗粒浓度和大小的变化反映了二十碳五烯酸的降 TG 作用。IPE 降低 LDL 颗粒浓度是 ω-3 治疗中的一个新发现，与此前报告的 IPE 在 TG 极高的患者中降低载脂蛋白 B 且不增加 LDL-C 一致。
NCT01047683。
