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J Am Coll Cardiol, 2002; 40:2125-2134
© 2002 by the American College of Cardiology Foundation
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CLINICAL STUDY

Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia

Michael H. Davidson, MD, FACC*,*, Thomas McGarry, MD, FACC{dagger}, Robert Bettis, MD{ddagger}, Lorenzo Melani, MD, PhD§, Leslie J. Lipka, MD, PhD, FACC§, Alexandre P. LeBeaut, MD§, Ramachandran Suresh, PhD§, Steven Sun, PhD§, Enrico P. Veltri, MD, FACC§ Ezetimibe Study Group

* Chicago Center for Clinical Research, Chicago, Illinois, USA
{dagger} Oklahoma Foundation for Cardiovascular Research, Oklahoma City, Oklahoma, USA
{ddagger} Clinical Research Advantage, Edmonds Family Medicine Clinic, Edmonds, Washington, USA
§ Schering-Plough Research Institute, Kenilworth, New Jersey, USA

Manuscript received April 11, 2002; revised manuscript received September 6, 2002, accepted September 20, 2002.

* Reprint requests and correspondence: Dr. Michael H. Davidson, Chicago Center for Clinical Research, 515 North State Street, Suite 2700, Chicago, Illinois 60610-4324 USA.
mdavidson{at}protocare.com

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.

METHODS: After dietary stabilization, a 2- to 12-week washout period, and a 4-week, single-blind, placebo lead-in period, patients with baseline low-density lipoprotein cholesterol (LDL-C) ≥145 mg/dl to ≤250 mg/dl and triglycerides (TG) ≤350 mg/dl were randomized to one of the following 10 groups administered daily for 12 consecutive weeks: ezetimibe 10 mg; simvastatin 10, 20, 40, or 80 mg; ezetimibe 10 mg plus simvastatin 10, 20, 40, or 80 mg; or placebo. The primary efficacy variable was percentage reduction from baseline to end point in direct LDL-C for the pooled ezetimibe plus simvastatin groups versus pooled simvastatin groups.

RESULTS: Ezetimibe plus simvastatin significantly improved LDL-C (p < 0.01), high-density lipoprotein cholesterol (HDL-C) (p = 0.03), and TG (p < 0.01) compared with simvastatin alone. Ezetimibe plus simvastatin (pooled doses) provided an incremental 13.8% LDL-C reduction, 2.4% HDL-C increase, and 7.5% TG reduction compared with pooled simvastatin alone. Coadministration of ezetimibe and simvastatin provided LDL-C reductions of 44% to 57%, TG reductions of 20% to 28%, and HDL-C increases of 8% to 11%, depending on the simvastatin dose. Ezetimibe 10 mg plus simvastatin 10 mg and simvastatin 80 mg alone each provided a 44% LDL-C reduction. The coadministration of ezetimibe with simvastatin was well tolerated, with a safety profile similar to those of simvastatin and of placebo.

CONCLUSIONS: When coadministered with simvastatin, ezetimibe provided significant incremental reductions in LDL-C and TG, as well as increases in HDL-C. Coadministration of ezetimibe with simvastatin was well tolerated and comparable to statin alone.

Abbreviations and Acronyms
  ALT
  alanine aminotransferase
  AST
  aspartate aminotransferase
  CPK
  creatine phosphokinase
  HDL-C
  high-density lipoprotein cholesterol
  LDL-C
  low-density lipoprotein cholesterol
  NCEP ATP
  National Cholesterol Education Program Adult Treatment Panel
  TC
  total cholesterol
  TG
  triglycerides
  ULN
  upper limit of normal




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