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

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

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Cardiovascular Division, Osaka National Hospital.
Division of Cardiology, Department of Medicine, Nihon University School of Medicine.
Cardiovascular Center, Osaka Gyoumeikan Hospital.
Department of Cardiovascular Medicine, Ehime Prefectural Imabari Hospital.
Division of Coronary Heart Disease, Hyogo College of Medicine.
Department of Cardiology, Hyogo Prefectural Awaji Medical Center.
Division of Cardiovascular Medicine, Akabane Central General Hospital.



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).


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.


Angioscopy; Ezetimibe; Intravascular ultrasound (IVUS); Plaque regression; Plaque stabilization

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