Journal Article

Dose-comparison study of the combination of ezetimibe and simvastatin (Vytorin) versus atorvastatin in patients with hypercholesterolemia: The Vytorin Versus Atorvastatin (VYVA) Study

Palmisano, Joanne, Abate, Nicola, Yuan, Zhong, Ballantyne, Christie M., King, Thomas R.

2005

Overview

Low-density lipoprotein cholesterol (LDL-C) is the primary therapeutic target in the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines. This study tested the hypothesis that ezetimibe/simvastatin, a lipid-lowering agent that inhibits both intestinal cholesterol absorption and cholesterol synthesis, provides greater LDL-C reductions than atorvastatin across dose ranges. This multicenter, double-blind, 6-week parallel-group study randomized 1902 patients with LDL-C above ATP III goal to atorvastatin (10, 20, 40, or 80 mg) or to ezetimibe/simvastatin (10/10, 10/20, 10/40, or 10/80 mg). Patients were stratified by prerandomization LDL-C level. At each milligram-equivalent statin dose comparison, and averaged across doses, ezetimibe/simvastatin provided greater LDL-C reductions (47%-59%) than atorvastatin (36%-53%). Ezetimibe/simvastatin 10/40 and 10/80 mg also provided significantly greater high-density lipoprotein cholesterol (HDL-C) increases than atorvastatin 40 and 80 mg. Triglyceride reductions were similar for all comparisons. More ezetimibe/simvastatin than atorvastatin patients with coronary heart disease (CHD) or CHD risk equivalents attained the ATP III LDL-C goal of <100 mg/dL and the optional LDL-C target of <70 mg/dL. C-reactive protein reductions were similar between treatment groups. Consecutive elevations in alanine aminotransferase and/or aspartate aminotransferase occurred in significantly more atorvastatin patients than ezetimibe/simvastatin patients. No myopathy or liver-related adverse events led to study discontinuation with either drug. Ezetimibe/simvastatin was more effective than atorvastatin in lowering LDL-C at each dose comparison and provided greater increases in HDL-C at the 40- and 80-mg statin dose. Ezetimibe/simvastatin is a highly efficacious, well-tolerated treatment option for hypercholesterolemic patients.

• Publisher: Mosby, Inc,Elsevier,Elsevier Limited
• Subject: Adult / Aged / Anticholesteremic Agents - administration & dosage / Azetidines - administration & dosage / Biological and medical sciences / C-Reactive Protein - drug effects / C-Reactive Protein - metabolism / Cardiology. Vascular system / Cardiovascular disease / Cholesterol / Cholesterol, HDL - drug effects / Cholesterol, HDL - metabolism / Cholesterol, LDL - drug effects / Cholesterol, LDL - metabolism / Disorders of blood lipids. Hyperlipoproteinemia / Double-Blind Method / Drug dosages / Drug therapy / Drug Therapy, Combination / Ezetimibe / Female / Humans / Hypercholesterolemia - drug therapy / Hypercholesterolemia - metabolism / Kinases / Male / Medical sciences / Metabolic diseases / Middle Aged / Population / Simvastatin - administration & dosage / Statins