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


RESULTS
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.


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.)
Ladenson
Paul W
PW
Division of Endocrinology and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.
Kristensen
Jens D
JD
Ridgway
E Chester
EC
Olsson
Anders G
AG
Carlsson
Bo
B
Klein
Irwin
I
Baxter
John D
JD
Angelin
Bo
B
D000328:Adult; D000813:Anilides / Q000009:adverse effects / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D013963:Thyroid Hormones / Q000097:blood; D014280:Triglycerides / Q000097:blood; D014284:Triiodothyronine / Q000031:analogs & derivatives
C526273:3-((3,5-dibromo-4-(4-hydroxy-3-(1-methylethyl)phenoxy)phenyl)amino)-3-oxopropanoic acid; D000813:Anilides; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008074:Lipoproteins; D013963:Thyroid Hormones; D014280:Triglycerides; D014284:Triiodothyronine