Long-term safety and tolerability of ezetimibe coadministered with simvastatin in hypercholesterolemic patients: a randomized, 12-month double-blind extension study.

Objectives: To assess the long-term safety and tolerability and to further evaluate the effect of ezetimibe plus simvastatin on LDL-C, HDL-C, and triglyceride levels in subjects with primary hypercholesterolemia.

Methods: This was a 12-month, double-blind, placebo-controlled extension study that enrolled patients with primary hypercholesterolemia who had successfully completed the 12-week, double-blind, placebo-controlled trial of ezetimibe coadministered with simvastatin. The initial dose administered to patients in the extension was ezetimibe 10 mg coadministered with simvastatin 10 mg with the option to up-titrate statin dosage if LDL-C goals were not met.

Simvastatin with or without ezetimibe in familial hypercholesterolemia.

Background: Ezetimibe, a cholesterol-absorption inhibitor, reduces levels of low-density lipoprotein (LDL) cholesterol when added to statin treatment. However, the effect of ezetimibe on the progression of atherosclerosis remains unknown.

Methods: We conducted a double-blind, randomized, 24-month trial comparing the effects of daily therapy with 80 mg of simvastatin either with placebo or with 10 mg of ezetimibe in 720 patients with familial hypercholesterolemia.

Effects of ezetimibe, simvastatin, atorvastatin, and ezetimibe-statin therapies on non-cholesterol sterols in patients with primary hypercholesterolemia.

Background: Levels of cholesterol are regulated by its synthesis, absorption, and elimination. Plasma levels of phytosterols (e.g.

Zetia: inhibition of Niemann-Pick C1 Like 1 (NPC1L1) to reduce intestinal cholesterol absorption and treat hyperlipidemia.

Zetia (ezetimibe) is a selective cholesterol absorption inhibitor, which potently inhibits the absorption of biliary and dietary cholesterol from the small intestine without affecting the absorption of fat-soluble vitamins, triglycerides or bile acids. Ezetimibe reduces the small intestinal enterocyte uptake and absorption of cholesterol by binding to Niemann-Pick C1 Like 1 (NPC1L1), which keeps cholesterol in the intestinal lumen for excretion. Ezetimibe undergoes glucuronidation to a single metabolite and localizes at the intestinal wall, where it binds with higher affinity for NPC1L1 than ezetimibe to prevent cholesterol absorption.

Projected coronary heart disease risk benefit with ezetimibe.

Low density lipoprotein (LDL) cholesterol and total cholesterol (TC) are the primary clinical parameters of interest for any cholesterol intervention. Clinicians are interested in how the reduction of these lipid parameters as well as increases in high density lipoprotein (HDL) relate to changes in coronary heart disease (CHD) risk. The objective of this analysis was to estimate the additional CHD risk reduction that could potentially be provided by co-administration of ezetimibe with statin therapy.

Pharmacodynamic and pharmacokinetic interaction between fenofibrate and ezetimibe.

Objective: The cholesterol absorption inhibitor, ezetimibe, significantly decreases low-density lipoprotein-cholesterol (LDL-C) levels in patients with primary hypercholesterolemia. The pharmacodynamic, pharmacokinetic, and safety profiles of ezetimibe and fenofibrate were evaluated alone and after co-administration in 32 subjects with primary hypercholesterolemia.

Research Design And Methods: This was a randomized, evaluator (single)-blind, placebo-controlled, parallel-group study.

Effects of ezetimibe on the pharmacodynamics and pharmacokinetics of lovastatin.

Background: Ezetimibe is a cholesterol absorption inhibitor which decreases low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. This study investigated the potential for pharmacodynamic and/or pharmacokinetic interactions between ezetimibe and lovastatin.

Methods: In a randomized, evaluator (single)-blind, placebo-controlled, parallel-group study, 48 healthy men with hypercholesterolemia (screening LDL-C >or= 130 mg/dL) who were stabilized and maintained on a National Cholesterol Education Program (NCEP) Step I diet were randomized to one of the following six oral treatments once daily for 14 days: lovastatin 20 mg; lovastatin 20 mg plus ezetimibe 5, 10, or 20 mg; lovastatin 40 mg plus ezetimibe 10mg; or placebo.

Effect of ezetimibe coadministered with atorvastatin in 628 patients with primary hypercholesterolemia: a prospective, randomized, double-blind trial.

Background: Despite the established efficacy of statins, many patients do not achieve recommended LDL cholesterol (LDL-C) goals. Contributing factors may be inadequate dosing, increased risk for adverse effects with high-dose monotherapy, and increased potential for intolerance and adverse effects with combinations of available agents.

Methods And Results: In a double-blind study, 628 patients with baseline LDL-C 145 to 250 mg/dL and triglycerides < or =350 mg/dL were randomly assigned to receive 1 of the following for 12 weeks: ezetimibe (10 mg/d); atorvastatin (10, 20, 40, or 80 mg/d); ezetimibe (10 mg) plus atorvastatin (10, 20, 40, or 80 mg/d); or placebo.

Efficacy and safety of ezetimibe coadministered with lovastatin in primary hypercholesterolemia.

This multicenter, randomized, double-blind, placebo-controlled clinical study assessed the efficacy and safety of ezetimibe administered with lovastatin in primary hypercholesterolemia. After dietary stabilization, a 2- to 12-week washout period, and a 4-week single-blind placebo lead-in period, 548 patients with low-density lipoprotein (LDL) cholesterol > or =145 mg/dl (3.75 mmol/L) and < or =250 mg/dl (6.

Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia.

Objectives: The purpose of this study was to assess the efficacy and safety of ezetimibe administered with simvastatin in patients with primary hypercholesterolemia.

Background: Despite the availability of statins, many patients do not achieve lipid targets. Combination therapy with lipid-lowering agents that act via a complementary pathway may allow additional patients to achieve recommended cholesterol goals.

Efficacy and safety of a potent new selective cholesterol absorption inhibitor, ezetimibe, in patients with primary hypercholesterolemia.

The efficacy and safety of ezetimibe, a new cholesterol absorption inhibitor, was evaluated in this randomized, double-blind, placebo-controlled trial of 892 patients with primary hypercholesterolemia. After > or =2 weeks on the National Cholesterol Education Program (NCEP) Step I or a stricter diet and a 4- to 8-week single-blind placebo lead-in, patients with low-density lipoprotein (LDL) cholesterol 130 to 250 mg/dl and triglycerides < or =350 mg/dl were randomized 3:1 to receive ezetimibe 10 mg or placebo orally each morning for 12 weeks. The primary efficacy end point was the percent reduction in direct plasma LDL cholesterol from baseline to end point.

Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin.

Aims: The primary aims of these two single-centre, randomized, evaluator-blind, placebo/positive-controlled, parallel-group studies were to evaluate the potential for pharmacodynamic and pharmacokinetic interaction between ezetimibe 0.25, 1, or 10 mg and simvastatin 10 mg (Study 1), and a pharmacodynamic interaction between ezetimibe 10 mg and simvastatin 20 mg (Study 2). Evaluation of the tolerance of the coadministration of ezetimibe and simvastatin was a secondary objective.