title: Ezetimibe/simvastatin 10/40 mg versus atorvastatin 40 mg in high cardiovascular risk patients with primary hypercholesterolemia: a randomized, double-blind, active-controlled, multicenter study.
abstract: BACKGROUND
  A considerable number of patients with severely elevated LDL-C do not achieve recommended treatment targets, despite treatment with statins. Adults at high cardiovascular risk with hypercholesterolemia and LDL-C ≥ 2.59 and ≤ 4.14 mmol/L (N = 250), pretreated with atorvastatin 20 mg were randomized to ezetimibe/simvastatin 10/40 mg or atorvastatin 40 mg for 6 weeks. The percent change in LDL-C and other lipids was assessed using a constrained longitudinal data analysis method with terms for treatment, time, time-by-treatment interaction, stratum, and time-by-stratum interaction. Percentage of subjects achieving LDL-C < 1.81 mmol/L, < 2.00 mmol/L, or < 2.59 mmol/L was assessed using a logistic regression model with terms for treatment and stratum. Tolerability was assessed.
  
  
  RESULTS
  Switching to ezetimibe/simvastatin resulted in significantly greater changes in LDL-C (-26.81% vs.-11.81%), total cholesterol (-15.97% vs.-7.73%), non-HDL-C (-22.50% vs.-10.88%), Apo B (-17.23% vs.-9.53%), and Apo A-I (2.56% vs.-2.69%) vs. doubling the atorvastatin dose (all p ≤ 0.002), but not HDL-C, triglycerides, or hs-CRP. Significantly more subjects achieved LDL-C < 1.81 mmol/L (29% vs. 5%), < 2.00 mmol/L (38% vs. 9%) or < 2.59 mmol/L (69% vs. 41%) after switching to ezetimibe/simvastatin vs. doubling the atorvastatin dose (all p < 0.001). The overall safety profile appeared generally comparable between treatment groups.
  
  
  CONCLUSIONS
  In high cardiovascular risk subjects with hypercholesterolemia already treated with atorvastatin 20 mg but not at LDL-C < 2.59 mmol/L, switching to combination ezetimibe/simvastatin 10/40 mg provided significantly greater LDL-C lowering and greater achievement of LDL-C targets compared with doubling the atorvastatin dose to 40 mg. Both treatments were generally well-tolerated.
  
  
  BACKGROUND
  Registered at clinicaltrials.gov: NCT00782184.
authors.affiliation: School of Medicine and Health Sciences, Monash University, 80100 Johor Bahru, Malaysia. pkhling@yahoo.co.uk
authors.forename: Paul Kah
authors.initials: PK
authors.lastname: Hing Ling
authors.forename: Fernando
authors.initials: F
authors.lastname: Civeira
authors.forename: Andrei Gheorghe
authors.initials: AG
authors.lastname: Dan
authors.forename: Mary E
authors.initials: ME
authors.lastname: Hanson
authors.forename: Rachid
authors.initials: R
authors.lastname: Massaad
authors.forename: Celine Le Bailly
authors.initials: Cle B
authors.lastname: De Tilleghem
authors.forename: Christopher
authors.initials: C
authors.lastname: Milardo
authors.forename: Joseph
authors.initials: J
authors.lastname: Triscari
mesh_terms: D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D001384:Azetidines / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D004311:Double-Blind Method; D004338:Drug Combinations; D000069438:Ezetimibe; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D019821:Simvastatin / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D004338:Drug Combinations; D006538:Heptanoic Acids; D008055:Lipids; D011758:Pyrroles; D002097:C-Reactive Protein; D000069059:Atorvastatin; D019821:Simvastatin; D000069438:Ezetimibe