Dr. John Baxter, director of the Genomic Medicine Program at The Methodist Hospital Research Institute, Houston, TX, and co-author for the study, stated that, "Our study has shown a dramatic reduction in the dangerous fats that cause heart disease, the number one killer of Americans."
"For patients taking a statin, this drug can further lower LDL cholesterol by 25 percent -- on top of what the statin is doing. It is also as potent in lowering triglycerides as any current medication available today," Baxter added. "It also lowers Lp(a), which is an under recognized factor that also causes atherosclerosis and is a common cause of heart attack in young people. Thus, eprotirome could be a major complement to the only current medication for this condition, niacin, which causes flushing side effects."
While statins remain the gold standard for cholesterol reduction today, they are still limited in helping patients reach strident goals set to reduce a patient's risk for heart disease and heart attack, and they can have significant side effects, Baxter added.
Results from the study show that eprotirome could be used in addition to statins to help patients who have not been able to reach their cholesterol goals, or could be used to reduce the statin dose to decrease statin side effects including muscle pain and bone loss.
The phase II clinical trial evaluated eprotirome, a liver selective thyroid hormone receptor agonist, and its ability to further reduce serum LDL cholesterol levels in statin-treated patients.
The study was a randomized, placebo-controlled, double-blind multi-center trial that lasted three months. It was designed to assess the safety and efficacy of eprotirome (KB2115) in lowering the serum concentration of LDL cholesterol and other atherogenic lipids in patients with high cholesterol who are already taking simvastatin or atorvastatin.
In all, 329 patients were screened for the study, of which 189 were randomized and included in the trial. In addition to statin treatment, they received either eprotirome 25, 50, or 100 mcg per day or placebo. Primary outcome was LDL cholesterol and secondary outcomes were changes in serum apo B, triglyceride, and Lp(a) concentrations. Safety monitoring included assessments of potential adverse thyroid hormone-like effects on the heart, bone, and pituitary.
The addition of eprotirome to statin treatment for 12 weeks resulted in placebo-adjusted reductions in serum LDL-cholesterol concentrations of -15 percent, -20 percent, and -26 percent with daily 25 mcg, 50 mcg and 100 mcg eprotirome, respectively. Similar reductions were seen in serum apo B (-14 percent, -19 percent, and -24 percent), triglycerides (-20 percent, -20 percent, and -37 percent), and Lp(a) (-17 percent, -22 percent, and -34 percent). These effects on atherogenic lipid variables were similar in magnitude to those found in a previous study where eprotirome was given as monotherapy, indicating a full additive effect on top of statins. Eprotirome therapy was clinically very well tolerated without adverse cardiac or bone or pituitary effects. The frequency, pattern and intensity of adverse events were similar in placebo and eprotirome-treated patients.
NEJM, March 11, 2010