title: Reductions in serum levels of LDL cholesterol, apolipoprotein B, triglycerides and lipoprotein(a) in hypercholesterolaemic patients treated with the liver-selective thyroid hormone receptor agonist eprotirome.
abstract: BACKGROUND
  Liver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia.
  
  
  METHODS
  We performed a multicentre, randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of eprotirome, a liver-selective thyroid hormone receptor agonist, in 98 patients with primary hypercholesterolaemia. After previous drug wash-out and dietary run-in, patients received 100 or 200 μg day(-1) eprotirome or placebo for 12 weeks. The primary end-point was change in serum LDL cholesterol; secondary end-points included changes in other lipid parameters and safety measures.
  
  
  RESULTS
  Eprotirome treatment at 100 and 200 μg daily reduced serum LDL cholesterol levels by 23 ± 5% and 31 ± 4%, respectively, compared with 2 ± 6% for placebo (P < 0.0001). Similar reductions were seen in non-HDL cholesterol and apolipoprotein (apo) B, whereas serum levels of HDL cholesterol and apo A-I were unchanged. There were also considerable reductions in serum triglycerides and lipoprotein(a), in particular in patients with elevated levels at baseline. There was no evidence of adverse effects on heart or bone and no changes in serum thyrotropin or triiodothyronine, although the thyroxine level decreased. Low-grade increases in liver enzymes were evident in most patients.
  
  
  CONCLUSIONS
  In hypercholesterolaemic patients, the liver-selective thyromimetic eprotirome decreased serum levels of atherogenic lipoproteins without signs of extra-hepatic side effects. Selective stimulation of hepatic thyroid hormone receptors may be an attractive way to modulate lipid metabolism in hyperlipidaemia.
authors.affiliation: Department of Endocrinology, Metabolism and Diabetes, Center for Biosciences, Karolinska Institutet At Karolinska University Hospital Huddinge, Stockholm, Sweden.|Center for Biosciences, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Angelin
authors.affiliation: Karo Bio AB, Huddinge, Sweden.
authors.forename: Jens D
authors.initials: JD
authors.lastname: Kristensen
authors.affiliation: Department of Endocrinology, Metabolism and Diabetes, Center for Biosciences, Karolinska Institutet At Karolinska University Hospital Huddinge, Stockholm, Sweden.|Center for Biosciences, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Eriksson
authors.affiliation: Karo Bio AB, Huddinge, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Carlsson
authors.affiliation: New York University School of Medicine, New York, NY, USA.
authors.forename: Irwin
authors.initials: I
authors.lastname: Klein
authors.affiliation: The Faculty of Health Sciences, Linköping University and Stockholm Heart Center, Linköping, Sweden.
authors.forename: Anders G
authors.initials: AG
authors.lastname: Olsson
authors.affiliation: Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, Aurora, CO, USA.
authors.forename: E
authors.initials: E
authors.lastname: Chester Ridgway
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Ladenson
mesh_terms: D000813:Anilides / Q000008:administration & dosage* / Q000009:adverse effects; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001055:Apolipoproteins B / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism; D008078:Cholesterol, LDL / Q000187:drug effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D008875:Middle Aged; D013972:Thyrotropin / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014284:Triiodothyronine / Q000378:metabolism
chemical_list: C526273:3-((3,5-dibromo-4-(4-hydroxy-3-(1-methylethyl)phenoxy)phenyl)amino)-3-oxopropanoic acid; D000813:Anilides; D000924:Anticholesteremic Agents; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D014280:Triglycerides; D014284:Triiodothyronine; D013972:Thyrotropin
keywords: cholesterol; hypercholesterolaemia; lipoprotein; liver; thyroid