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

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.