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Use of the Thyroid Hormone Analogue Eprotirome in Statin-Treated Dyslipidemia
Johns Hopkins University.
Karo Bio AB.
University of Colorado.
Linköping University, Department of Medical and Health Sciences, Internal Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Department of Endocrinology and Gastroenterology UHL.
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2010 (English)In: Obstetrical and Gynecological Survey, ISSN 0029-7828, E-ISSN 1533-9866, Vol. 65, no 8, 512-513 p.Article in journal, Editorial material (Other academic) Published
Abstract [en]

Statins effectively reduce levels of serum cholesterol and lower the risk of cardiovascular disease, but have limited effectiveness if stringent goals for serum low-density lipoprotein (LDL) cholesterol levels are not met or adverse effects develop, requiring a dose reduction or drug discontinuation. Previous studies have shown that thyroid hormone and some of its metabolites reduce levels of serum LDL cholesterol and have potentially favorable actions on other lipoproteins. The studies were discontinued because of reports of adverse effects on heart and bone, and possible deaths. In a recent report, eprotirome, a thyromimetic compound with minimal uptake in nonhepatic-tissues, was shown to reduce levels of serum total and LDL cholesterol and apolipoprotein B without apparent side effects in patients not receiving statin therapy. This randomized, placebo-controlled, double-blind, multicenter trial investigated the safety and efficacy of eprotirome in lowering the level of serum LDL cholesterol in patients with hypercholesterolemia who already were receiving simvastatin or atorvastatin. The aim of the study was to determine whether adding eprotirome to statin therapy would provide additional lipid-lowering actions without producing adverse extrahepatic thyromimetic effects. Patients were randomly assigned to receive daily oral doses of 25, 50, or 100 mcg of eprotirome or a placebo for 12 weeks. The primary study outcome was changes in serum LDL cholesterol. The potential adverse thyromimetic effects on the heart, bone, and pituitary were examined. Treatment of patients for 12 weeks already receiving statins with either placebo or eprotirome at a dose of 25, 50, or 100 mu g reduced the mean level of serum LDL cholesterol from 141 mg per deciliter (3.6 mmol per liter) at baseline to 127, 113, 99, and 94 mg per deciliter (3.3, 2.9, 2.6, and 2.4 mmol per liter), respectively; this represented a mean reduction from baseline of 7%, 22%, 28%, and 32%, respectively. Similar reductions were found in the secondary study outcomes, which included serum levels of apolipoprotein B, triglycerides, and Lp(a) lipoprotein. No evidence of adverse effects of eprotirome on the heart, bone, or pituitary was noted. Although reductions in serum levels of thyroxine occurred in some patients who received eprotirome, there were no changes in levels of thyrotropin or triiodothyronine. These findings demonstrate that the addition of eprotirome to statin therapy produces substantial further reductions in serum LDL cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B. The drug appears to have an excellent safety profile.

Place, publisher, year, edition, pages
Lippincott Williams & Wilkins, 2010. Vol. 65, no 8, 512-513 p.
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Obstetrics, Gynecology and Reproductive Medicine
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URN: urn:nbn:se:liu:diva-61179DOI: 10.1097/OGX.0b013e3181f07bedISI: 000283264700019Scopus ID: 2-s2.0-78049377970OAI: oai:DiVA.org:liu-61179DiVA: diva2:361039
Available from: 2010-11-08 Created: 2010-11-05 Last updated: 2017-12-12Bibliographically approved

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Olsson, Anders G

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Internal MedicineFaculty of Health SciencesDepartment of Endocrinology and Gastroenterology UHL
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