Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia.

Dyslipidemia increases the risk of atherosclerotic cardiovascular disease and is incompletely reversed by statin therapy alone in many patients. Thyroid hormone lowers levels of serum low-density lipoprotein (LDL) cholesterol and has other potentially favorable actions on lipoprotein metabolism. Consequently, thyromimetic drugs hold promise as lipid-lowering agents if adverse effects can be avoided.
We performed a randomized, placebo-controlled, double-blind, multicenter trial to assess the safety and efficacy of the thyromimetic compound eprotirome (KB2115) in lowering the level of serum LDL cholesterol in patients with hypercholesterolemia who were already receiving simvastatin or atorvastatin. In addition to statin treatment, patients received either eprotirome (at a dose of 25, 50, or 100 microg per day) or placebo. Secondary outcomes were changes in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Patients were monitored for potential adverse thyromimetic effects on the heart, bone, and pituitary.
The addition of placebo or eprotirome at a dose of 25, 50, or 100 microg daily to statin treatment for 12 weeks reduced the mean level of serum LDL cholesterol from 141 mg per deciliter (3.6 mmol per liter) to 127, 113, 99, and 94 mg per deciliter (3.3, 2.9, 2.6, and 2.4 mmol per liter), respectively, (mean reduction from baseline, 7%, 22%, 28%, and 32%). Similar reductions were seen in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Eprotirome therapy was not associated with adverse effects on the heart or bone. No change in levels of serum thyrotropin or triiodothyronine was detected, although the thyroxine level decreased in patients receiving eprotirome.
In this 12-week trial, the thyroid hormone analogue eprotirome was associated with decreases in levels of atherogenic lipoproteins in patients receiving treatment with statins. (ClinicalTrials.gov number, NCT00593047.)
AuthorsPaul W Ladenson, Jens D Kristensen, E Chester Ridgway, Anders G Olsson, Bo Carlsson, Irwin Klein, John D Baxter, Bo Angelin
JournalThe New England journal of medicine (N Engl J Med) Vol. 362 Issue 10 Pg. 906-16 (Mar 11 2010) ISSN: 1533-4406 [Electronic] United States
PMID20220185 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Copyright2010 Massachusetts Medical Society
Chemical References
  • 3-((3,5-dibromo-4-(4-hydroxy-3-(1-methylethyl)phenoxy)phenyl)amino)-3-oxopropanoic acid
  • Anilides
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins
  • Thyroid Hormones
  • Triglycerides
  • Triiodothyronine
  • Adult
  • Anilides (adverse effects, therapeutic use)
  • Cholesterol, LDL (blood)
  • Double-Blind Method
  • Drug Therapy, Combination
  • Dyslipidemias (blood, drug therapy)
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
  • Lipoproteins (blood)
  • Male
  • Middle Aged
  • Thyroid Hormones (blood)
  • Triglycerides (blood)
  • Triiodothyronine (analogs & derivatives)

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