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

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

Research output: Contribution to journalArticlepeer-review

Abstract

Background: 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. Methods: 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 μg 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. Results: The addition of placebo or eprotirome at a dose of 25, 50, or 100 μg 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. Conclusions: 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.)

Original languageEnglish (US)
Pages (from-to)906-916
Number of pages11
JournalNew England Journal of Medicine
Volume362
Issue number10
DOIs
StatePublished - Mar 11 2010

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia'. Together they form a unique fingerprint.

Cite this