Long-term effects of ezetimibe-plus-statin therapy on low-density lipoprotein cholesterol levels as compared with double-dose statin therapy in patients with coronary artery disease

Atherosclerosis. 2012 Oct;224(2):454-6. doi: 10.1016/j.atherosclerosis.2012.07.036. Epub 2012 Aug 4.

Abstract

Objective: To assess the mechanism of long-term LDL-C-lowering effect of ezetimibe-plus-statin.

Methods: Coronary artery disease patients whose LDL-C ≥ 70 mg/dL after treatment with atorvastatin 10 mg/day or rosuvastatin 2.5 mg/day were randomly assigned to receive ezetimibe 10 mg/day + statin (n = 78) or double-dose statin (n = 72) for 52 weeks.

Results: Greater LDL-C reduction was observed and maintained until 52 weeks in ezetimibe-plus-statin, while LDL-C levels re-increased after 12 weeks in double-dose statin. Although lathosterol/TC increased, campesterol/TC decreased more in ezetimibe-plus-statin. In contrast, lathosterol/TC unchanged and campesterol/TC increased, increasing campesterol/lathosterol ratio for 52 weeks in double-dose statin. Plasma PCSK9 levels were higher in double-dose statin than in ezetimibe-plus-statin at 12 weeks, but similar at 52 weeks.

Conclusion: Although the difference in PCSK9 between 2 groups was transient, that in both campesterol and lathosterol persisted until 52 weeks. These results demonstrated simultaneous inhibition of cholesterol absorption and synthesis provides stable and greater decrease in LDL-C levels.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anticholesteremic Agents / administration & dosage*
  • Anticholesteremic Agents / adverse effects
  • Atorvastatin
  • Azetidines / administration & dosage*
  • Azetidines / adverse effects
  • Biomarkers / blood
  • Cholesterol / analogs & derivatives
  • Cholesterol / blood
  • Cholesterol, LDL / blood*
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / drug therapy*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Ezetimibe
  • Female
  • Fluorobenzenes / administration & dosage*
  • Fluorobenzenes / adverse effects
  • Heptanoic Acids / administration & dosage*
  • Heptanoic Acids / adverse effects
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Japan
  • Male
  • Middle Aged
  • Phytosterols / blood
  • Proprotein Convertase 9
  • Proprotein Convertases / blood
  • Prospective Studies
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Pyrroles / administration & dosage*
  • Pyrroles / adverse effects
  • Rosuvastatin Calcium
  • Serine Endopeptidases / blood
  • Sulfonamides / administration & dosage*
  • Sulfonamides / adverse effects
  • Time Factors
  • Treatment Outcome

Substances

  • Anticholesteremic Agents
  • Azetidines
  • Biomarkers
  • Cholesterol, LDL
  • Fluorobenzenes
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Phytosterols
  • Pyrimidines
  • Pyrroles
  • Sulfonamides
  • campesterol
  • lathosterol
  • Rosuvastatin Calcium
  • Cholesterol
  • Atorvastatin
  • PCSK9 protein, human
  • Proprotein Convertase 9
  • Proprotein Convertases
  • Serine Endopeptidases
  • Ezetimibe