ZETIA(R) with fenofibrate provided complementary lipid lowering efficacy

Ezetimibe and fenofibrate treatment well-tolerated over 12 weeks -


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 B 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."


ZETIA co-administered with fenofibrate provided significant LDL cholesterol reduction compared to fenofibrate alone


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