title: Icosapent ethyl, a pure EPA omega-3 fatty acid: effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study).
abstract: BACKGROUND
  Icosapent ethyl (IPE; formerly AMR101) is a high-purity prescription form of eicosapentaenoic acid ethyl ester. In the MARINE study we evaluated the efficacy and safety of IPE in patients with very high triglycerides (TG; ≥500 mg/dL) and previously demonstrated significant reductions in TG levels with no significant increases in low-density lipoprotein (LDL) cholesterol levels.
  
  
  OBJECTIVE
  In this follow-up, exploratory analysis, we report the effects of IPE on lipoprotein particle concentration and size.
  
  
  METHODS
  MARINE was a phase 3, multicenter, placebo-controlled, randomized, double-blind, 12-week study. Hypertriglyceridemic patients (N = 229) were randomized to three treatment groups: IPE 4 g/day, IPE 2 g/day, or placebo. Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy.
  
  
  RESULTS
  Compared with placebo, IPE 4 g/day significantly reduced median concentrations of large very-low-density lipoprotein (VLDL; -27.9%; P = .0211), total LDL (-16.3%; P = .0006), small LDL (-25.6%; P < .0001), and total high-density lipoprotein (HDL; -7.4%; P = .0063) particles and reduced VLDL particle size (-8.6%; P = .0017). In this patient population with TG ≥500 mg/dL, IPE did not significantly change the overall sizes of LDL or HDL particles.
  
  
  CONCLUSIONS
  IPE 4 g/day significantly reduced large VLDL, total LDL, small LDL, and total HDL particle concentrations and VLDL particle size in patients with TG ≥500 mg/dL. Changes in VLDL particle concentration and size reflect the TG-lowering effects of eicosapentaenoic acid. The reduction in LDL particle concentration with IPE is novel among ω-3 therapies and is consistent with the previously reported reduction in apolipoprotein B and lack of LDL-C increase with IPE in patients with very high TG levels.
  
  
  BACKGROUND
  NCT01047683.
authors: Louisville Metabolic and Atherosclerosis Research Center, Louisville, KY 40213, USA. hbaysmd@aol.com
authors: Harold E
authors: HE
authors: Bays
authors: Rene A
authors: RA
authors: Braeckman
authors: Christie M
authors: CM
authors: Ballantyne
authors: John J
authors: JJ
authors: Kastelein
authors: James D
authors: JD
authors: Otvos
authors: William G
authors: WG
authors: Stirtan
authors: Paresh N
authors: PN
authors: Soni
mesh_terms: D000328:Adult; D001055:Apolipoproteins B / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003327:Coronary Disease / Q000473:pathology / Q000517:prevention & control; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000188:drug therapy / Q000473:pathology; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*
chemical_list: D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; C035276:eicosapentaenoic acid ethyl ester; D015118:Eicosapentaenoic Acid