Effect of Ezetimibe on Stabilization and Regression of Intracoronary Plaque - The ZIPANGU Study

Circ J. 2017 Oct 25;81(11):1611-1619. doi: 10.1253/circj.CJ-17-0193. Epub 2017 Jun 8.


Background: Diminishing yellow color is associated with plaque stabilization. We assessed the hypothesis that a combination of ezetimibe and statin provides more effective plaque stabilization and regression than statin alone as assessed by plaque color.Methods and Results:Stable coronary artery disease patients (n=131) who underwent elective percutaneous coronary intervention and had yellow plaques were randomized to combination therapy (atorvastatin 10-20 mg and ezetimibe 10 mg/day; Group C) or statin monotherapy (atorvastatin 10-20 mg; Group M). Changes in plaque color and plaque volume during 9 months were assessed by angioscopy and intravascular ultrasound. Low-density lipoprotein cholesterol (LDL-C) decreased from 103±28 to 63±18 mg/dL in Group C (P<0.001) and from 100±28 to 75±17 mg/dL in Group M (P<0.001). Yellow color grade decreased significantly in both Group M (2.1±1.1 vs. 1.7±1.0, P=0.005) and Group C (2.2±1.2 vs. 1.8±1.2, P=0.002), but did not differ between the groups. %plaque volume did not change in Group M (48.5±10.2% vs. 48.2±10.4%, P=0.4), but decreased significantly in Group C (50.0±9.8% vs. 49.3±9.8%, P=0.03).

Conclusions: Compared with statin monotherapy, combination therapy with ezetimibe further reduced LDL-C levels. Significant plaque volume reduction was achieved by the combination therapy, but not statin monotherapy; however, plaque stabilization was similarly achieved by both therapies. Furthermore, reduction in plaque volume was dependent on reduction in LDL-C, regardless of whether it was achieved by statin alone or statin plus ezetimibe.

Keywords: Angioscopy; Ezetimibe; Intravascular ultrasound (IVUS); Plaque regression; Plaque stabilization.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Atorvastatin / pharmacology
  • Atorvastatin / therapeutic use
  • Cholesterol, LDL / blood
  • Cholesterol, LDL / drug effects
  • Color
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / pathology
  • Drug Therapy, Combination / methods*
  • Drug Therapy, Combination / standards
  • Ezetimibe / pharmacology*
  • Ezetimibe / therapeutic use
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / drug therapy*
  • Plaque, Atherosclerotic / pathology


  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Atorvastatin
  • Ezetimibe