Icosapent ethyl (eicosapentaenoic acid ethyl ester): Effects on remnant-like particle cholesterol from the MARINE and ANCHOR studies.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on plasma and red blood cell fatty acids in patients with very high triglyceride levels (results from the MARINE study).

INTRODUCTION: Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester. We evaluated IPE's effects on plasma and red blood cell (RBC) fatty acids (FA) and the relationship to triglyceride (TG) lowering. MATERIALS AND METHODS: This was a predefined, exploratory analysis (N=229) of FA plasma concentration and RBC membrane content from the double-blind, placebo-controlled MARINE study. RESULTS: Mean placebo-adjusted plasma EPA levels increased from baseline by 792% and 402% and the arachidonic acid/EPA plasma ratio decreased from baseline by 99% and 88% with IPE 4 g/day and 2 g/day, respectively (all P<.0001). Overall, the fractional pool of omega-3 FAs increased; there was a decrease or no change for omega-6 FAs. The increase in EPA levels with increased IPE dose corresponded with the TG-lowering effect. Similar FA shifts were observed in RBCs. CONCLUSIONS: IPE significantly increased plasma and RBC FAs, which correlated to TG lowering.

Icosapent ethyl for the treatment of hypertriglyceridemia.

INTRODUCTION: Icosapent ethyl (IPE; Vascepa) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester recently approved in 2012 to reduce triglyceride (TG) levels in adult patients with severe (≥ 500 mg/dL) hypertriglyceridemia. Elevated TG levels are associated with increased risk for coronary heart disease. Currently available TG-lowering agents (fibrates, niacins, omega-3 fatty acid products containing both EPA and docosahexaenoic acid [DHA]) may be associated with adverse effects such as flushing, hepatotoxicity, myopathy, elevated glucose levels, and/or increases in low-density lipoprotein cholesterol (LDL-C). AREAS COVERED: This review describes IPE chemistry, pharmacokinetics, and clinical studies. In two Phase III randomized, placebo-controlled trials, one in patients with very high TG levels (≥ 500 mg/dL; MARINE) and the other in statin-treated patients at high cardiovascular risk with well-controlled LDL-C and residual high TG levels (≥ 200 to < 500 mg/dL; ANCHOR), IPE lowered levels of TG, non-high-density lipoprotein cholesterol, and other atherogenic lipoproteins without increasing LDL-C levels. EXPERT OPINION: IPE is safe and effective for managing high TG levels, and it offers a new alternative with potential benefits over currently available treatments for dyslipidemia. The ongoing cardiovascular outcomes REDUCE-IT trial will provide valuable information on the efficacy of IPE to prevent cardiovascular events in high-risk patients already taking statins.

PX3.102, a novel chinese herb extract, diminishes chronic airway allograft rejection.

More effective immunosuppressants are needed to improve lung-transplantation survival. PX3.102 is a novel immunosuppressant isolated from a mixture of traditional Chinese herbs. We tested its protective role on chronic lung rejection in the heterotopic tracheal transplant model. C57BL/6 mice received BALB/c tracheal grafts and were treated with PX3.102, cyclosporine A, or vehicle. PX3.102 improved tracheal allograft lumen patency (*P<0.01 vs. vehicle and P=0.14 vs. cyclosporine A) but not epithelialization (P>0.2 vs. vehicle). Subsequent in vitro studies demonstrated that PX3.10 was toxic to fully differentiated human tracheal epithelial cells in a dose-dependent manner. PX3.102 markedly suppressed antigen-specific lymphocyte proliferation in vitro at a concentration 10 times lower than cyclosporine A. In conclusion, PX3.102, a promising and potent immunosuppressant, although exhibiting toxicity to airway epithelial cells at high doses, is effective in inhibiting chronic airway allograft rejection.