Abstract

Background: Remnant-like particle cholesterol (RLP-C) represents the cholesterol carried by partially catabolized triglyceride (TG)-rich lipoproteins such as very-low-density lipoproteins (VLDL) in the fasted state and chylomicron remnants in the post-prandial state. Increased RLP-C levels are atherogenic and may increase the risk of atherosclerotic cardiovascular disease. Long-chain polyunsaturated omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid reduce RLP-C levels. Icosapent ethyl (IPE) is a high-purity prescription form of EPA ethyl ester approved to reduce TG levels in patients with severe (>=500 mg/dL) hypertriglyceridemia. Objective: To evaluate the effects of IPE on RLP-C levels in patients from the MARINE and ANCHOR studies. Methods: MARINE (TG >=500 and <=2000 mg/dL; N=229) and ANCHOR (TG >=200 and <500 mg/dL despite statin control of low-density lipoprotein cholesterol; N=702) were both 12-week, phase 3, double-blind studies that randomized patients to IPE 4 g/day, 2 g/day, or placebo. This analysis assessed the median percentage change from baseline to study end in RLP-C levels compared with placebo. Serum RLP-C was measured with an immunoseparation assay (Polymedco). Results: In both the MARINE (n=218 with RLP-C data) and ANCHOR (n=252 with RLP-C data) studies, compared with placebo, IPE 4 g/day (Table) and 2 g/day reduced RLP-C levels. Compared with placebo, the approved IPE dose of 4 g/day also reduced RLP-C to a greater extent in subgroups with higher baseline TG levels, reduced RLP-C in statin-treated patients in the MARINE study, and reduced RLP-C in patients receiving moderate- to high-intensity statins in the ANCHOR study. Conclusions: Compared with placebo, IPE reduced RLP-C levels in patients in the MARINE and ANCHOR studies, including significant reductions in RLP-C in hypertriglyceridemic patients with TG >=200 mg/dL or >=500 mg/dL receiving statin therapy.

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