【原】纯EPA显著降低女性甘油三酯

　　对于女性，降低甘油三酯药物的有效性和安全性数据有限。根据两项随机双盲安慰剂对照研究（MARINE和ANCHOR）结果，美国食品药品管理局（FDA）批准一种仅含二十碳五烯酸（EPA）的高纯度海洋鱼油制剂（EPA≥96%）用于治疗高甘油三酯血症。对此，美国哥伦比亚大学、贝勒医学院、休斯敦卫理公会德贝基心血管中心、路易斯维尔代谢与动脉粥样硬化研究中心、杜克大学等机构对MARINE和ANCHOR进行了女性亚组分析，研究结果发表于美国心脏病学会《美国心脏病杂志》。

• MARINE研究共入组高甘油三酯（500～2000mg/dl）患者229例，ANCHOR研究共入组高甘油三酯（200～500mg/dl）患者702例，均随机分配口服纯EPA或安慰剂12周，结果发现纯EPA显著降低甘油三酯、非高密度脂蛋白胆固醇、载脂蛋白B、脂蛋白相关磷脂酶A2、极低密度脂蛋白胆固醇、总胆固醇，而不增加低密度脂蛋白胆固醇。耐受性良好，安全性与安慰剂相似。

• MARINE: 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). Am J Cardiol. 2011;108(5):682-690.

• ANCHOR: Efficacy and Safety of Eicosapentaenoic Acid Ethyl Ester (AMR101) Therapy in Statin-Treated Patients With Persistent High Triglycerides (from the ANCHOR Study). Am J Cardiol. 2012;110(7):984-992.

　　本亚组分析从MARINE和ANCHOR研究入组215例甘油三酯200～2000mg/dl的女性，分析了纯EPA对甘油三酯（主要有效性变量）及其他引起动脉粥样硬化和炎症指标的影响。

• MARINE：治疗组18例、对照组18例

• ANCHOR：治疗组91例、对照组88例

　　结果发现，MARINE和ANCHOR研究的女性每天口服4g共12周的纯EPA与安慰剂相比：

• 甘油三酯显著降低22.7%（P=0.0327）和21.5%（P＜0.0001），而不增加低密度脂蛋白胆固醇。

• 非高密度脂蛋白胆固醇显著降低15.7%（P=0.0082）和14.2%（P＜0.0001）。

• 总胆固醇显著降低14.9%（P=0.0023）和12.1%（P＜0.0001）。

• 血浆和红细胞EPA显著增加＞500%（所有P＜0.001）。

• 纯EPA的耐受性良好，不良事件分布与整体研究结果相似。

　　因此，每天口服4g的纯EPA与安慰剂相比，显著降低了女性的甘油三酯和其他动脉粥样硬化指标，而不增加低密度脂蛋白胆固醇。心血管结局研究——EPA减少心血管事件干预研究（REDUCE-IT）正在评估上述结果的临床意义。

小调查

Am J Cardiol. 2017;119(3):397-403.

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

Mosca L, Ballantyne CM, Bays HE, Guyton JR, Philip S, Doyle RT Jr, Juliano RA.

Columbia University Medical Center, New York, New York; Baylor College of Medicine, 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.

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.

PMID: 27939227

DOI: 10.1016/j.amjcard.2016.10.027