Effect of combination therapy of ezetimibe and rosuvastatin on regression of coronary atherosclerosis in Japanese patients with stable coronary artery disease

Abstract

Background: Recent clinical trials have demonstrated that intensive low-density lipoprotein-cholesterol (LDL-C) lowering therapy by strong statins could prevent recurrent cardiovascular event and have beneficial regressive effects on coronary plaques. Otherwise, the use of ezetimibe in combination with statin has been reported to provide greater reduction in LDL-C level than statin monotherapy. However, it is not established whether additional LDL-C lowering achieved with the addition of ezetimibe to statin monotherapy will lead to further reduction in coronary plaque volume. Methods: In this prospective, open-label, randomized study, 40 patients with stable coronary artery disease (CAD) requiring percutaneous coronary intervention (PCI), whose LDL-C levels were higher than 100 mg/dl, were divided into combination therapy group (n=21, rosuvastatin 5mg plus ezetimibe 10mg daily) or statin monotherapy group (n=19, rosuvastatin 5mg daily). Serial volumetric intravascular ultrasound (IVUS) analysis were performed at baseline and after 6 months of follow-up for a non-PCI site. Results: LDL-C level was significantly decreased by 54.1% in the combination group (from 132.7±31.7 mg/dl to 59.5±17.1 mg/dl, p<0.001) vs. 42.1% in the monotherapy group (from 122.0±15.7 mg/dl to 69.1±19.7 mg/dl, p<0.001). Plaque volume (PV) was significantly reduced in the combination group (14.2±12.9% decrease) compared with the monotherapy group (2.1±17.0% decrease; p=0.016). Moreover, percent change in PV showed a significantly positive correlation with percent change and nominal change of LDL-C (r=0.403, p=0.011, and r=0.418, p=0.008, respectively), and percent change of non high-density lipoprotein cholesterol (r=0.380, p=0.024). It also showed a significant positive correlation with follow-up small dense LDL level (r=0.455, p=0.006). Conclusions: Aggressive LDL-C lowering therapy by ezetimibe in addition to statin may exert significant regression of coronary plaque volume compared with usual-dose statin monotherapy in patients with stable CAD.