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

Bo Angelin, Jens D. Kristensen, Mats Eriksson, Bo Carlsson, Irwin Klein, Anders G. Olsson, E. Chester Ridgway, Paul W Ladenson

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish (US)
Pages (from-to)331-342
Number of pages12
JournalJournal of Internal Medicine
Volume277
Issue number3
DOIs
StatePublished - Mar 1 2015

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Thyroid Hormone Receptors
Lipoprotein(a)
Apolipoproteins B
LDL Cholesterol
Triglycerides
Hormones
Liver
Serum
Placebos
Safety
Apolipoprotein A-I
Triiodothyronine
Thyrotropin
Dyslipidemias
Hypercholesterolemia
Hyperlipidemias
Thyroxine
Lipid Metabolism
Double-Blind Method
HDL Cholesterol

Keywords

  • Cholesterol
  • Hypercholesterolaemia
  • Lipoprotein
  • Liver
  • Thyroid

ASJC Scopus subject areas

  • Internal Medicine
  • Medicine(all)

Cite this

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. / Angelin, Bo; Kristensen, Jens D.; Eriksson, Mats; Carlsson, Bo; Klein, Irwin; Olsson, Anders G.; Chester Ridgway, E.; Ladenson, Paul W.

In: Journal of Internal Medicine, Vol. 277, No. 3, 01.03.2015, p. 331-342.

Research output: Contribution to journalArticle

Angelin, Bo ; Kristensen, Jens D. ; Eriksson, Mats ; Carlsson, Bo ; Klein, Irwin ; Olsson, Anders G. ; Chester Ridgway, E. ; Ladenson, Paul W. / 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. In: Journal of Internal Medicine. 2015 ; Vol. 277, No. 3. pp. 331-342.
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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. 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.",
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AU - Angelin, Bo

AU - Kristensen, Jens D.

AU - Eriksson, Mats

AU - Carlsson, Bo

AU - Klein, Irwin

AU - Olsson, Anders G.

AU - Chester Ridgway, E.

AU - Ladenson, Paul W

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N2 - 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. 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.

AB - 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. 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.

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KW - Hypercholesterolaemia

KW - Lipoprotein

KW - Liver

KW - Thyroid

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