title: Consistency of lipid-altering effects of ezetimibe/simvastatin across gender, race, age, baseline low density lipoprotein cholesterol levels, and coronary heart disease status: results of a pooled retrospective analysis.
abstract: BACKGROUND
  The combination tablet containing ezetimibe and simvastatin (EZE/SIMVA), inhibits both the intestinal absorption and endogenous production of cholesterol, providing significantly greater low-density lipoprotein cholesterol (LDL-C) lowering than EZE or SIMVA alone. The purpose of this pooled analysis was to evaluate the consistency of efficacy (i.e., between-treatment difference) of EZE/SIMVA versus SIMVA within several selected subgroups of patients with primary hypercholesterolemia.
  
  
  METHODS
  For the present analysis, data were pooled from three similarly designed, 12-week, randomized, double-blind, placebo-controlled factorial studies consisting of 3083 patients with primary hypercholesterolemia (n = 311 in placebo group; n = 302 in EZE group; n = 1234 in pooled SIMVA group; n = 1236 in pooled EZE/SIMVA group). In these clinical studies, primary hypercholesterolemia was defined as an LDL-C value between 145 and 250 mg/dL inclusive and a triglyceride (TG) level of less than 350 mg/dL. The results for the pooled SIMVA and pooled EZE/SIMVA groups were used for the present analyses. The pooled analyses focused on the consistency of the between-treatment differences (i.e., incremental effect) for EZE/SIMVA (pooled across doses) versus SIMVA (pooled across doses) on various lipid and non-lipid parameters within different patient subgroups defined according to gender, race (Caucasian, Non-Caucasian), baseline age (< 65, > or = 65 years), baseline LDL-C (< 160, > or = 160 mg/dL), and coronary heart disease (CHD) history. Tolerability was also examined for pooled EZE/SIMVA and pooled SIMVA within these selected subgroups. In a modified intention-to-treat analysis, an ANOVA model was used for testing the consistency of pooled treatment effects on lipid and non-lipid parameters within each selected subgroup.
  
  
  RESULTS
  For the entire cohort, baseline lipid profiles were similar for the patients in the pooled EZE/SIMVA group compared with those in the pooled SIMVA group. Treatment with EZE/SIMVA led to significant (p < 0.001) incremental improvements in LDL-C, non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B, TG and high sensitivity C-reactive protein compared to SIMVA, across the entire cohort. These changes were consistent within each of the selected subgroups. Moreover, more patients attained LDL-C goal levels < 100 mg/dL with EZE/SIMVA than with SIMVA in the entire cohort and this was consistent across all subgroups, except baseline LDL-C. In this pooled retrospective analysis, treatment with EZE/SIMVA was generally well tolerated across subgroups, with a safety profile similar to SIMVA monotherapy. Although this pooled analysis was performed on a large cohort of patients with primary hypercholesterolemia, the results of this analysis were specific for this select patient population and generalizations to other populations should be applied with caution.
  
  
  CONCLUSIONS
  The enhanced lipid-altering effects of EZE/SIMVA versus those of SIMVA observed in the entire cohort were consistent within all subgroups examined. EZE/SIMVA represents an effective and well-tolerated therapeutic option for the treatment of a wide range of patient subgroups with primary hypercholesterolemia.
authors.affiliation: Lipid Clinic, Medical Department, Rikshospitalet, Oslo, Norway. leiv.ose@klinmed.uio.no
authors.forename: Leiv
authors.initials: L
authors.lastname: Ose
authors.forename: Arvind
authors.initials: A
authors.lastname: Shah
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Jennifer
authors.initials: J
authors.lastname: Rotonda
authors.forename: Darbie
authors.initials: D
authors.lastname: Maccubbin
authors.forename: Diane
authors.initials: D
authors.lastname: Tribble
authors.forename: Enrico
authors.initials: E
authors.lastname: Veltri
authors.forename: Yale
authors.initials: Y
authors.lastname: Mitchel
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001384:Azetidines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D008078:Cholesterol, LDL / Q000187:drug effects; D017326:Clinical Trials, Phase III as Topic; D003327:Coronary Disease / Q000208:ethnology; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000208:ethnology; D008074:Lipoproteins / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012307:Risk Factors; D012737:Sex Factors; D019821:Simvastatin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D001384:Azetidines; D008078:Cholesterol, LDL; D008074:Lipoproteins; D019821:Simvastatin; D000069438:Ezetimibe