title: Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs. statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials.
abstract: OBJECTIVE
  This post hoc analysis compared the lipid-altering efficacy and safety of ezetimibe 10 mg plus statin (EZE/statin) vs. statin monotherapy in hypercholesterolaemic patients with and without diabetes.
  
  
  METHODS
  A pooled analysis of 27 previously published, randomized, double-blind, active- or placebo-controlled clinical trials comprising 21 794 adult patients with (n = 6541) and without (n = 15253) diabetes receiving EZE/statin or statin alone for 4-24 weeks evaluated percentage change from baseline in lipids and other parameters. Consistency of the treatment effect across the subgroups was tested using treatment × subgroup interaction. No multiplicity adjustments were made.
  
  
  RESULTS
  Treatment effects within both subgroups were generally consistent with the overall population. EZE/statin was more effective than statin alone in improving low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs), non-HDL-C, apolipoprotein (apo) B and high-sensitivity C-reactive protein (hs-CRP) in the overall population and both subgroups. Patients with diabetes achieved significantly larger reductions in LDL-C, TC and non-HDL-C compared with non-diabetic patients. Incidences of adverse events or creatine kinase elevations were similar between groups. A small but significantly higher incidence of alanine aminotransferase or aspartate aminotransferase elevations was seen in patients receiving EZE/statin (0.6%) vs. statin monotherapy (0.3%) in the overall population.
  
  
  CONCLUSIONS
  Treatment with EZE/statin vs. statin monotherapy provided significantly larger reductions in LDL-C, TC, TG, non-HDL-C, apo B and hs-CRP and significantly greater increases in HDL-C, with a similar safety profile in patients with and without diabetes. Reductions in LDL-C, TC and non-HDL-C were larger in patients with diabetes than in patients without diabetes.
authors.affiliation: Division of Endocrinology, Keenan Research Centre in the Li Ka Shing Knowledge Institute of St. Michael's Hospital, University of Toronto, Toronto, Canada. leiterl@smh.ca
authors.forename: L A
authors.initials: LA
authors.lastname: Leiter
authors.forename: D J
authors.initials: DJ
authors.lastname: Betteridge
authors.forename: M
authors.initials: M
authors.lastname: Farnier
authors.forename: J R
authors.initials: JR
authors.lastname: Guyton
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.forename: A
authors.initials: A
authors.lastname: Shah
authors.forename: A O
authors.initials: AO
authors.lastname: Johnson-Levonas
authors.forename: P
authors.initials: P
authors.lastname: Brudi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001384:Azetidines / Q000008:administration & dosage* / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D019821:Simvastatin / Q000008:administration & dosage* / Q000494:pharmacology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin; D000069438:Ezetimibe