Baylor College of Medicine and the Houston Methodist DeBakey Heart and Vascular Center, 6565 Fannin St. MSA 601, Houston, TX 77030, USA.
Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY, USA.
Atherosclerosis. 2016 Oct;253:81-87. doi: 10.1016/j.atherosclerosis.2016.08.005. Epub 2016 Aug 20.
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.
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.
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).
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.
残粒样颗粒胆固醇（RLP-C）具有致动脉粥样硬化作用，可能增加动脉粥样硬化性心血管疾病风险。依泽替米贝是一种高纯度的二十碳五烯酸乙酯处方药（批准作为饮食辅助疗法，用于降低甘油三酯（TG）水平，适用人群为 TG 水平≥500mg/dL[≥5.65mmol/L]的成年患者，每日 4g）。在 MARINE 和 ANCHOR 研究中，依泽替米贝降低了 TG 和其他致动脉粥样硬化脂质参数水平，而 LDL-C 水平没有增加。这项探索性分析评估了依泽替米贝对计算和直接测量的 RLP-C 的影响。
MARINE（TGs≥500 且≤2000mg/dL[≥5.65mmol/L 且≤22.6mmol/L]）和 ANCHOR（TGs≥200 且<500mg/dL[≥2.26 且<5.65mmol/L]，尽管 LDL-C 受到他汀类药物的控制）是两项为期 12 周、双盲、III 期研究，将成年患者随机分为依泽替米贝 4g/天、2g/天或安慰剂组。该分析评估了直接测量（免疫分离测定法）RLP-C 水平的基线至研究结束时的中位数百分比变化（MARINE，n=218；ANCHOR，n=252）以及全人群中计算的 RLP-C 水平。
依泽替米贝 4g/天与安慰剂相比，在 MARINE 中直接测量的 RLP-C 水平显著降低了-29.8%（p=0.004），在 ANCHOR 中降低了-25.8%（p=0.0001），并且在基线 TG 水平较高与较低的亚组中，在服用他汀类药物与未服用他汀类药物的患者中（MARINE），以及在服用中/高强度他汀类药物与低强度他汀类药物的患者中（ANCHOR），依泽替米贝也更能降低直接测量的 RLP-C 水平。在 ANCHOR 和 MARINE 中，计算的和直接测量的 RLP-C 的基线、治疗结束和百分比变化值之间存在很强的相关性（0.73-0.92；p<0.0001）。
依泽替米贝 4g/天与 MARINE 和 ANCHOR 研究中升高的 TG 水平患者的安慰剂相比，显著降低了计算的和直接测量的 RLP-C 水平。
