This study was sponsored by Karo Bio AB, Huddinge, Sweden.
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
Article first published online: 16 MAY 2014
© 2014 The Association for the Publication of the Journal of Internal Medicine
Journal of Internal Medicine
Volume 277, Issue 3, pages 331–342, March 2015
How to Cite
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. J Intern Med 2015; 277: 331–342., , , , , , , (Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm; Karo Bio AB, Huddinge, Sweden; New York University School of Medicine, New York, NY, USA; Linköping University and Stockholm Heart Center, Sweden; University of Colorado School of Medicine, Aurora, CO, USA; The Johns Hopkins University School of Medicine, Baltimore, MD, USA).
- Issue published online: 13 FEB 2015
- Article first published online: 16 MAY 2014
- Accepted manuscript online: 22 APR 2014 10:51PM EST
- Swedish Research Council
Liver-selective thyromimetic agents could provide a new approach for treating dyslipidaemia.
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.
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.
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.