Effects of Ezetimibe-Statin Combination Therapy on Coronary Atherosclerosis in Acute Coronary Syndrome

Background: The results of previous clinical trials on the effects of ezetimibe-statin combination therapy on atherosclerosis are inconsistent, and the anti-atherosclerotic effect of ezetimibe remains controversial. Methods and Results: We conducted a prospective, randomized open-label study at 10 centers. One hundred and twenty-eight statin-naive patients with acute coronary syndrome (ACS) undergoing intravascular ultrasound (IVUS)-guided percutaneous coronary intervention were randomized to receive either 2 mg/day pitavastatin plus 10 mg/day ezetimibe, or 2 mg/day pitavastatin. One hundred and 3 patients had evaluable IVUS of non-culprit coronary lesions at baseline and at follow-up. The primary endpoint was the percentage change in non-culprit coronary plaque volume (PV) and lipid PV on integrated backscatter IVUS. Mean low-density lipoprotein cholesterol was reduced from 123 mg/dL to 64 mg/dL in the combination therapy group (n=50) and 126 mg/dL to 87 mg/dL in the statin alone group (n= 53; between-group difference, 16.9%, P<0.0001). The percent change in PV was -5.1% in the combination therapy group and -6.2% in the statin alone group (P=0.66), although both groups had reduction of PV compared with baseline (both P<0.01). The percent change in lipid PV did not differ between the groups (4.3 vs. -3.0%, P=0.37). Conclusions: In statin-naive patients with ACS, combined therapy with ezetimibe and statin did not result in a significant change in coronary plaque regression or tissue component compared with statin alone.