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

• Published in: The American heart journal Vol. 149; no. 3; pp. 464 - 473
• Main Authors: Ballantyne, Christie M., Abate, Nicola, Yuan, Zhong, King, Thomas R., Palmisano, Joanne
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.03.2005; Elsevier; Elsevier Limited
• Subjects: 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; Human; Simvastatin; Metabolic diseases; Cardiovascular disease; Lipids; Hyperlipoproteinemia; Lipoprotein; Posology; Cholesterol; Hypercholesterolemia; Heart disease; Atorvastatin; Dyslipemia; Dose; Comparative study
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/j.ahj.2004.11.023

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.