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

Authors

  • Bo Angelin,

    Corresponding author
    1. Department of Endocrinology, Metabolism and Diabetes, Center for Biosciences, Karolinska Institutet At Karolinska University Hospital Huddinge, Stockholm, Sweden
    2. Center for Biosciences, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
    • Correspondence: Dr. Bo Angelin, Department of Endocrinology, Metabolism, and Diabetes C2-94, Karolinska University Hospital Huddinge, S-141 86 Stockholm, Sweden. (fax: +46 8 711 0710; e-mail: bo.angelin@ki.se).

    Search for more papers by this author
  • Jens D. Kristensen,

    1. Karo Bio AB, Huddinge, Sweden
    Search for more papers by this author
  • Mats Eriksson,

    1. Department of Endocrinology, Metabolism and Diabetes, Center for Biosciences, Karolinska Institutet At Karolinska University Hospital Huddinge, Stockholm, Sweden
    2. Center for Biosciences, Department of Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
    Search for more papers by this author
  • Bo Carlsson,

    1. Karo Bio AB, Huddinge, Sweden
    Search for more papers by this author
  • Irwin Klein,

    1. New York University School of Medicine, New York, NY, USA
    Search for more papers by this author
  • Anders G. Olsson,

    1. The Faculty of Health Sciences, Linköping University and Stockholm Heart Center, Linköping, Sweden
    Search for more papers by this author
  • E. Chester Ridgway,

    1. Division of Endocrinology, Metabolism and Diabetes, University of Colorado School of Medicine, Aurora, CO, USA
    Search for more papers by this author
  • Paul W. Ladenson

    1. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Search for more papers by this author

  • This study was sponsored by Karo Bio AB, Huddinge, Sweden.

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 (< 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.

Conclusion

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.

Ancillary