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

Diabetes Obes Metab. 2011 Jul;13(7):615-28. doi: 10.1111/j.1463-1326.2011.01383.x.

Abstract

Aim: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticholesteremic Agents / administration & dosage*
  • Anticholesteremic Agents / pharmacology
  • Azetidines / administration & dosage*
  • Azetidines / pharmacology
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Therapy, Combination
  • Ezetimibe
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Simvastatin / administration & dosage*
  • Simvastatin / pharmacology
  • Treatment Outcome
  • Young Adult

Substances

  • Anticholesteremic Agents
  • Azetidines
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin
  • Ezetimibe