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

Abstract

(IVUS), respectively, in the TWINS 3 and TOGETHAR 4 studies.In the present ZIPANGU (ezetimibe clinical investigation for regression of intracoronary plaque evaluated by angioscopy and ultrasound) study, we compared the effect of combination therapy (statin+ezetimibe) and monotherapy (statin alone) through examination of the plaque stabilization effect by angioscopy and the plaque regression effect by IVUS. Methods Study DesignThis study was a multicenter, prospective, randomized, L ow-density lipoprotein cholesterol (LDL-C)-lowering therapy has been shown to be effective for primary and secondary prevention of cerebrovascular and cardiovascular diseases. Ezetimibe, an inhibitor of the Niemann-Pick C1-like 1 cholesterol transporter, is a relatively new drug for LDL-C-lowering therapy. 1 Combination therapy with a statin and ezetimibe produced better clinical outcomes than statin monotherapy in the IMPROVE-IT (Improved Reduction of Outcomes; Vytorin Efficacy International Trial) study. 2 However, the plaque stabilization and regression effects of these 2 therapies have not been adequately evaluated. We previously investigated the plaque stabilization effect and plaque regression effect of statin therapies by angioscopy and intravascular ultrasound 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.

Vulnerable Plaque, Characteristics, Detection, and Potential Therapies

“…Ezetimibe ameliorates endothelial dysfunction and atherosclerosis regression in coronary arteries [126]. Results from an ezetimibe clinical investigation on the regression of intracoronary plaque evaluated by angioscopy and ultrasound (ZIPANGU) in patients with stable CVD have suggested that ezetimibe and atorvastatin are more effective for plaque regression than statin alone [165]. Antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9) are used to lower LDL in the management of atherosclerotic CVD risk [161,164].…”

Intensive statin versus low-dose statin + ezetimibe treatment for fibrous cap thickness of coronary vulnerable plaques

“…[ 23 ] However, whether the combination therapy had a superior effect on stabilizing coronary VP, especially increasing the FCT remains unclear. [ 24 – 26 ] Few studies have evaluated the effect of combination therapy on the FCT of VPs. One study showed that when ezetimibe was combined with statin, it could further increase the FCT more than statin monotherapy [ 27 ] ; this finding is similar to our result.…”

Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease: Implications for Evaluation and Targets for Treatment of Dyslipidemia Based on Recent Guidelines

“…Ezetimibe decreases small intestine cholesterol absorption by inhibiting the Niemann-Pick C1-Like 1 (NPC1L1) transporter [172,177]. While the exact mechanisms of the effect of ezetimibe on atherosclerosis by itself are not as well defined as the effects of statins on atherosclerotic plaque progression and stabilization, the addition of ezetimibe to statins has been shown to regress plaque burden, reduce plaque volume, and promote plaque stabilization [178,179]. PSCK9 works by interacting in with hepatic LDLR and enhancing the degradation of the receptor by hepatic lysosomes, with PSCK9 inhibitors thus mitigating the PSCK9-mediated turnover of hepatic LDLR and prolonging LDLR lifespan and uptake of circulating LDL-C [180].…”