title: Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200-500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study.
abstract: BACKGROUND
  Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester indicated as an adjunct to diet to reduce triglyceride (TG) levels in adult patients with severe (≥500 mg/dL) hypertriglyceridemia. ANCHOR was a 12-week, phase 3 study that evaluated the efficacy and safety of IPE in patients (N = 702) with residual high fasting TG levels (≥200 and <500 mg/dL) despite having optimized low-density lipoprotein cholesterol (LDL-C) levels (≥40 and <100 mg/dL) on statin therapy. Among patients randomized to IPE (4 g/day or 2 g/day) or placebo, 514 (73%) had diabetes mellitus.
  
  
  METHODS
  A post hoc subgroup analysis of the ANCHOR study was conducted to assess the effects of IPE on median placebo-adjusted percent change from baseline in efficacy end point parameters in 3 subgroups: total (all subjects with diabetes-overall median baseline glycosylated hemoglobin A₁c [A₁c] = 6.8%), better-controlled diabetes (below median baseline A1c), and less-controlled diabetes (above median baseline A1c).
  
  
  RESULTS
  Baseline efficacy parameters were similar among all groups except high-sensitivity C-reactive protein (hsCRP), which was higher in the total and less-controlled diabetes groups. Compared with placebo, IPE 4 g/day significantly reduced TG, non-high-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol (VLDL-C), lipoprotein-associated phospholipase A2, apolipoprotein B (Apo B), total cholesterol, high-density lipoprotein cholesterol, VLDL-TG, oxidized LDL, and remnant-like particle cholesterol in all 3 diabetes groups, LDL-C in the total diabetes group, and hsCRP in the total and less-controlled diabetes groups. Decreases in hsCRP and Apo B were much greater in patients with less-controlled diabetes. There were no significant increases in fasting plasma glucose, A1c, insulin, or homeostasis model assessment-estimated insulin resistance in any group.
  
  
  CONCLUSIONS
  IPE 4 g/day significantly improved lipid and lipid-related parameters without worsening glycemic control in patients with diabetes and mixed dyslipidemia, with possibly greater effects among those with less-controlled diabetes.
  
  
  BACKGROUND
  Clinicaltrials.gov Identifier NCT01047501.
authors.forename: Eliot A
authors.initials: EA
authors.lastname: Brinton
authors.forename: Christie M
authors.initials: CM
authors.lastname: Ballantyne
authors.forename: Harold E
authors.initials: HE
authors.lastname: Bays
authors.forename: John J
authors.initials: JJ
authors.lastname: Kastelein
authors.forename: Rene A
authors.initials: RA
authors.lastname: Braeckman
authors.forename: Paresh N
authors.initials: PN
authors.lastname: Soni
mesh_terms: D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015118:Eicosapentaenoic Acid / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D018836:Inflammation Mediators / Q000097:blood*; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood*
chemical_list: D015415:Biomarkers; D008078:Cholesterol, LDL; D015118:Eicosapentaenoic Acid; D006442:Glycated Hemoglobin; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D000960:Hypolipidemic Agents; D018836:Inflammation Mediators; D014280:Triglycerides; C517652:hemoglobin A1c protein, human; C035276:eicosapentaenoic acid ethyl ester