title: Icosapent ethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies.
abstract: BACKGROUND
  Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid ethyl ester approved by the US Food and Drug Administration as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. In addition to TG-lowering effects, IPE also reduces non-high-density lipoprotein cholesterol and apolipoprotein B levels without significantly increasing low-density lipoprotein cholesterol (LDL-C) in patients with very high TG levels ≥500 mg/dL (MARINE study) and in patients with well-controlled LDL-C and residually high TG levels 200-500 mg/dL (ANCHOR study). This analysis examined the effect of IPE on inflammatory markers in patients from MARINE and ANCHOR.
  
  
  METHODS
  MARINE (N = 229) and ANCHOR (N = 702) were Phase III, double-blind studies that randomized hypertriglyceridemic patients to IPE 4 g/day, 2 g/day, or placebo. This analysis assessed the median placebo-adjusted percentage change from baseline in markers representing various stages of atherosclerotic inflammation such as intercellular adhesion molecule-1 (ICAM-1), oxidized low-density lipoprotein (Ox-LDL), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP).
  
  
  RESULTS
  Compared to placebo, IPE 4 g/day significantly decreased Ox-LDL (13 %, p < 0.0001, ANCHOR), Lp-PLA(2) (14 %, p < 0.001, MARINE; 19 %, p < 0.0001, ANCHOR), and hsCRP levels (36 %, p < 0.01, MARINE; 22 %, p < 0.001, ANCHOR), but did not significantly change ICAM-1 and IL-6 levels. In the MARINE study, IPE 2 g/day did not significantly change ICAM-1, Ox-LDL, Lp-PLA(2), IL-6, or hsCRP levels. Also, compared to placebo in the ANCHOR study, IPE 2 g/day significantly decreased Lp-PLA(2) levels (8 %, p < 0.0001), but did not significantly change levels of other assessed inflammatory markers.
  
  
  CONCLUSIONS
  Compared to placebo, in hypertriglyceridemic patients, IPE 4 g/day significantly decreased Ox-LDL, Lp-PLA(2), and hsCRP levels.
authors: Louisville Metabolic and Atherosclerosis Research Center, 3288 Illinois Avenue, Louisville, KY 40213, USA. HBaysMD@aol.com
authors: Harold E
authors: HE
authors: Bays
authors: Christie M
authors: CM
authors: Ballantyne
authors: Rene A
authors: RA
authors: Braeckman
authors: William G
authors: WG
authors: Stirtan
authors: Paresh N
authors: PN
authors: Soni
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D004952:Esters; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood* / Q000188:drug therapy* / Q000453:epidemiology; D007249:Inflammation / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D018836:Inflammation Mediators / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D004952:Esters; D018836:Inflammation Mediators; D015118:Eicosapentaenoic Acid