Results from a new study showed that coadministration of Zetia (ezetimibe) and fenofibrate significantly reduced LDL ("bad") cholesterol (LDL-C), non-high density lipoprotein cholesterol (non-HDL-C) and apo B1 in patients with mixed hyperlipidemia and high LDL cholesterol when compared to fenofibrate alone.
The study, presented today at the 2004 American Heart Association Scientific Sessions, also showed that significant increases in HDL cholesterol and decreases in trigycerides (TG) similar to those seen with fenofibrate alone were seen in patients on Zetia co-administered with fenofibrate. The treatment with Zetia and fenofibrate for 12 weeks was also well-tolerated with a safety profile comparable to fenofibrate monotherapy. The label for Zetia indicates that the safety and effectiveness of Zetia with fibrates have not been established, therefore co-administration with fibrates is not recommended.
"This is the first large study to indicate that co-administration of Zetia and fenofibrate significantly lowers LDL cholesterol and non-HDL cholesterol more than fenofibrate alone in a mixed hyperlipidemia population. This study revealed that when diet changes alone were not sufficient in mixed hyperlipidemia, the co-administration of ezetimibe and fenofibrate significantly lowered LDL cholesterol, compared to fenofibrate alone. Zetia co-administered with fenofibrate also improved HDL cholesterol and triglyceride levels similar to fenofibrate alone," said Mason Wright Freeman, M.D., chief, Lipid Metabolism Unit, Massachusetts General Hospital. "Mixed hyperlipidemia is a metabolic disorder characterized by elevated LDL cholesterol, non HDL-C and TG and reduced levels of HDL cholesterol. Co-administration of Zetia and fenofibrate is not indicated for use in the label for Zetia, however further studies in these populations are certainly warranted to confirm these findings."
In a multicenter, randomized, double-blind, placebo-controlled, parallel arm trial, 619 patients were randomized in a 3:3:3:1 ratio to one of four daily treatments for 12 weeks: Zetia 10 mg (n=185), fenofibrate 160 mg (n=188), Zetia 10 mg plus fenofibrate 160 mg (n=183) and placebo (n=63). The study population was comprised of 619 patients, ages 18 to 75 with mixed hyperlipidemia after a six to eight week washout and dietary run-in period. Baseline LDL cholesterol levels ranged from 130 to 220 mg/dL (100 to 180 mg/dL for patients with type 2 diabetes) and triglycerides (TG) from 200 to 500 mg/dL; patients with a history of coronary heart disease (CHD), CHD-equivalent disease (except for type 2 diabetes) or CHD risk greater than 20 percent (except for type 2 diabetes) as defined by NCEP ATP III criteria were excluded.
The primary endpoint of this study compared the LDL cholesterol lowering efficacy of Zetia plus fenofibrate versus fenofibrate alone. After 12 weeks, the co-administration of Zetia and fenofibrate significantly reduced LDL cholesterol, non-HDL cholesterol, and apo B to a greater extent than Zetia alone or fenofibrate alone (p<0.001). Zetia and fenofibrate co-administration and fenofibrate alone both significantly increased HDL cholesterol levels by 19 percent and significantly reduced TG levels by 44 percent. Treatment with Zetia coadministered with fenofibrate, Zetia alone, and fenofibrate alone were all well-tolerated. Treatment with Zetia with fenofibrate was well tolerated over the 12 week study.