title: Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance.
abstract: BACKGROUND
  Once-daily, oral ETC-1002 reduces low-density lipoprotein cholesterol (LDL-C) and has beneficial effects on other cardiometabolic risk factors but has not been examined in statin intolerant patients.
  
  
  OBJECTIVE
  To study the efficacy and safety of ETC-1002 (a novel LDL-C-lowering agent) in patients with hypercholesterolemia and a history of statin intolerance.
  
  
  METHODS
  Patients intolerant to at least 1 statin were entered into this multicenter, double-blind, 8-week trial. Participants were required to have a history of muscle complaints that developed during statin treatment and resolved within 4 weeks of statin discontinuation. Patients (n = 56) were randomized in a 2:1 ratio to ETC-1002 60 mg daily or placebo. The ETC-1002 dose was increased at 2-week intervals to 120 mg, 180 mg, and 240 mg. The primary end point was the percentage change from baseline to week 8 in calculated LDL-C.
  
  
  RESULTS
  ETC-1002 reduced LDL-C 28.7% more than placebo (95% confidence interval, -35.4 to -22.1; P < .0001). ETC-1002 significantly reduced non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Triglycerides and high-density lipoprotein cholesterol did not change with ETC-1002 treatment. Sixty-two percent of patients receiving ETC-1002 and none in the placebo group achieved the 2004 National Cholesterol Education Program Adult Treatment Panel III LDL-C goal (P < .0001). Muscle-related adverse events occurred with similar frequency in the placebo and ETC-1002 treatment groups, causing no discontinuations in ETC-1002-treated patients.
  
  
  CONCLUSIONS
  ETC-1002 appears to be effective at reducing LDL-C and was well tolerated in patients with statin-associated muscle complaints. Longer and larger studies are required to confirm the absence of muscle side effects.
authors.affiliation: Department of Cardiology, Hartford Hospital, Hartford, CT, USA. Electronic address: paul.thompson@hhchealth.org.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Thompson
authors.affiliation: PMG Research of Raleigh, Raleigh, NC, USA.
authors.forename: John
authors.initials: J
authors.lastname: Rubino
authors.affiliation: Department of Cardiology, Wilmington Health, Wilmington, NC, USA; PMG Research of Wilmington, Wilmington, NC, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Janik
authors.affiliation: Esperion Therapeutics, Inc., Ann Arbor, MI, USA.
authors.forename: Diane E
authors.initials: DE
authors.lastname: MacDougall
authors.affiliation: United BioSource Corporation, Ann Arbor, MI, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: McBride
authors.affiliation: Esperion Therapeutics, Inc., Ann Arbor, MI, USA.
authors.forename: Janice R
authors.initials: JR
authors.lastname: Margulies
authors.affiliation: Esperion Therapeutics, Inc., Ann Arbor, MI, USA.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Newton
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D008078:Cholesterol, LDL / Q000097:blood; D003998:Dicarboxylic Acids / Q000008:administration & dosage*; D004311:Double-Blind Method; D005227:Fatty Acids / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D008078:Cholesterol, LDL; D003998:Dicarboxylic Acids; D005227:Fatty Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides; C581236:8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
keywords: ETC-1002; Hypercholesterolemia; LDL-cholesterol; Muscle complaints; Statin intolerance