title: Ezetimibe coadministered with simvastatin in patients with primary hypercholesterolemia.
abstract: OBJECTIVE
  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) > or =145 mg/dl to < or =250 mg/dl and triglycerides (TG) < or =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.
authors.affiliation: Chicago Center for Clinical Research, Illinois 60610, USA. mdavidson@protocare.com
authors.forename: Michael H
authors.initials: MH
authors.lastname: Davidson
authors.forename: Thomas
authors.initials: T
authors.lastname: McGarry
authors.forename: Robert
authors.initials: R
authors.lastname: Bettis
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Melani
authors.forename: Leslie J
authors.initials: LJ
authors.lastname: Lipka
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: LeBeaut
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Suresh
authors.forename: Steven
authors.initials: S
authors.lastname: Sun
authors.forename: Enrico P
authors.initials: EP
authors.lastname: Veltri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001384:Azetidines / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D008055:Lipids; D019821:Simvastatin; D000069438:Ezetimibe