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

doi:10.1016/j.ahj.2004.11.023

American Heart Journal

Volume 149, Issue 3, March 2005, Pages 464-473

https://doi.org/10.1016/j.ahj.2004.11.023 Get rights and content

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Section snippets

Study design

This multicenter, double-blind, randomized, active-controlled, 8-arm parallel-group study (10 weeks, with 4-week placebo/diet run-in period followed by 6 weeks of active treatment) was designed to evaluate the efficacy and safety of ezetimibe/simvastatin versus atorvastatin monotherapy across their respective dose ranges in patients with hypercholesterolemia. The protocol was approved by appropriate institutional review boards, and all patients provided written informed consent before

Patients

Of 4343 patients screened, a total of 1902 patients (951 each to ezetimibe/simvastatin and to atorvastatin) from 216 sites in the United States were randomized in a 1:1:1:1:1:1:1:1 ratio to each of the 8 treatment arms. Patients were primarily excluded from randomization for failure to meet eligibility criteria (1953), withdrawal of consent (282), and loss to follow-up during the placebo/diet run-in phase (75). Of the 1902 patients randomized, 1847 (97.1%) completed the study; 55 (2.9%)

Discussion

In this study, dual inhibition of cholesterol biosynthesis and absorption provided by ezetimibe/simvastatin was overall the more-effective option in reduction of LDL-C and for attainment of LDL-C treatment goals compared with atorvastatin. Averaged across the dose range, and at each milligram-equivalent statin dose comparison, patients treated with ezetimibe/simvastatin demonstrated significantly greater reductions in LDL-C compared with patients treated with atorvastatin monotherapy. A

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

Background

Methods

Results

Conclusions

Section snippets

Study design

Patients

Discussion

Am. J. Cardiol.

Am. J. Cardiol.

J. Am. Coll. Cardiol.

Am. J. Cardiol.

Am. J. Cardiol.

Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)

JAMA

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