Effects of Ezetimibe, A New Cholesterol Absorption Inhibitor, on Plasma Lipids in Patients with Primary Hypercholesterolemia - Effects of Ezetimibe, A New Cholesterol Absorption Inhibitor, on Plasma Lipids in Patients with Primary Hypercholesterolemia

Description:

The goal of this study was to assess the safety and efficacy of the cholesterol absorption blocker agent ezetimibe (Zetia) in men and women with primary hypercholesterolemia.

Study Design

Study Design:

Patients Enrolled: 827
Female: 54

Patient Populations:

>18 years with and LDL-C of at least 130 mg/dl and triglycerides <350 mg/dl.

Primary Endpoints:

percentage reduction in direct LDL-C

Drug/Procedures Used:

A multicenter randomized double blind controlled trial comparing ezetimibe 10 mg/d with placebo in mean and women >18 years with and LDL-C of at least 130 mg/dl and triglycerides <350 mg/dl. Adequate wash out of lipid altering agents and an NCEP step I or stricter diet was provided and maintained during the 4 week single blind placebo run-in and 12-week double-blind treatment phase with a 3:1 ratio of active drug to placebo. Primary endpoint was percentage reduction in direct LDL-C.

Principal Findings:

827 patients were randomized (622 active drug) with an average age of 57 years, 32% > 64 years, 54% female, average BMI 29kg/m2, and prior lipid lowering drug use in 25%. Mean baseline LDL-C was 163mg/dl, apo B 161mg/dl, apo A-1 151mg/dl, HDL-C 50mg/dl, and triglycerides 160mg/dl. Ezetimibe reduced LDL-C by 18% compared with a 0.8% increase with placebo, reduced apo B by 15%, LDL-C:HDL-C by 18%, and Lp (a) by 7.5%, and increased HDL2-C by 5% (all p<0.01 vs baseline with no effect by placebo). The effect on LDL-C was not influenced by gender, age, menopause, BMI, diabetes, baseline lipids, or the number of risk factors. Treatment adverse events were reported in 61% on ezetimibe and 65% on placebo. Ezetimibe had no effect on plasma cortisol before and after corticotropin stimulation and no effect on the levels on lipid soluble vitamins.

Interpretation:

Among men and women with primary hypercholesterolemia, Ezetimibe significantly reduces LDL-C and favorably affects other lipids, is well tolerated, and an effective new option for lipid management. Ezetimibe can be used alone in statin intolerant patients and is particularly useful in combination with the statins. The combination of ezetimibe 10mg with the starting dose of a statin provides about the same LDL-C lowering as a quadrupling of the statin dose, the advantage being possibly less hepatotoxicity and possibly cost saving. The cost of ezetimibe is about $35/month. Of course it has none of the non-lipid benefits of the statins, but the increase in HDL2-C is an unexpected gain.

References:

Knopp RH, Gitter H, Truit T, et al, for the Ezetimibe Study Group. Effects of Ezetimibe, A New Cholesterol Absorption Inhibitor, on Plasma Lipids in Patients with Primary Hypercholesterolemia. Eur Heart J 2003;24:729-41.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Homozygous Familial Hypercholesterolemia, Hypertriglyceridemia, Lipid Metabolism, Nonstatins, Statins, Diet

Keywords: Apolipoprotein A-I, Cost Savings, Hypercholesterolemia, Vitamins, Menopause, Cholesterol, Body Mass Index, Azetidines, Diet, Triglycerides, Hydrocortisone, Diabetes Mellitus


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