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.)