title: Rationale and design of a randomized clinical study to investigate the effect of ezetimibe, a cholesterol absorption inhibitor, on the regression of intracoronary plaque evaluated by non-obstructive angioscopy and ultrasound: The ZIPANGU study.
abstract: OBJECTIVE
  It is well recognized that low-density lipoprotein cholesterol (LDL-C)-lowering therapy is effective for primary and secondary prevention of cerebrovascular/cardiovascular disease. Ezetimibe, an inhibitor of the Niemann-Pick C1-Like 1 cholesterol transporter, is a relatively new drug for LDL-C-lowering therapy in addition to statins. However, comparison between an aggressive LDL-C-lowering therapy with a combination of statin and ezetimibe versus a standard LDL-C-lowering therapy with statin alone is still unclear in terms of their effects on stabilization and volume regression of coronary plaque. The ZIPANGU (Ezetimibe clinical investigation for the regression of intracoronary plaque evaluated by angioscopy and ultrasound) study is aimed at comparing these two types of therapy based on indices of plaque characteristics using non-obstructive coronary angioscopy and intravascular ultrasound.
  
  
  METHODS
  The study is a multi-center, prospective, randomized, open-label, blinded-endpoint trial. Through a centralized enrollment method, patients will be allocated to either monotherapy with atorvastatin alone or to combination therapy with atorvastatin (maximum: 20mg/day) and ezetimibe (10mg/day). The target LDL-C level will be <100mg/dL for the monotherapy group and <70mg/dL for the combination therapy group. At the baseline and the follow-up period of 9 months, non-obstructive coronary angioscopy and intravascular ultrasound will be performed to compare the changes in plaque color and volume between the two groups.
  
  
  CONCLUSIONS
  The ZIPANGU study will clarify whether combination therapy with statins and ezetimibe is better for stabilizing coronary plaque as secondary prevention than monotherapy by statins alone. The study will give new insights into lipid-lowering guidelines in Japan.
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: hiro.takafumi@nihon-u.ac.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Hiro
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirayama
authors.affiliation: Cardiovascular Division, Osaka Police Hospital, Osaka, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ueda
authors.affiliation: Cardiovascular Center, Amagasaki Central Hospital, Amagasaki, Japan.
authors.forename: Sei
authors.initials: S
authors.lastname: Komatsu
authors.affiliation: Department of Cardiovascular Medicine, Ehime Prefectural Imabari Hospital, Imabari, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuoka
authors.affiliation: Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
authors.forename: Tadateru
authors.initials: T
authors.lastname: Takayama
authors.affiliation: Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center Hospital, Suita, Japan.
authors.forename: Masaharu
authors.initials: M
authors.lastname: Ishihara
authors.affiliation: Hyogo Prefectural Awaji Medical Center, Sumoto, Japan.
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Division of Cardiovascular Medicine, Keiai Hospital, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Saito
authors.affiliation: Cardiovascular Center, Amagasaki Central Hospital, Amagasaki, Japan; Second Research Team, J-MIC Committee, Japan Health Promotion Foundation, Tokyo, Japan.
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Kodama
mesh_terms: D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000069059:Atorvastatin; D001384:Azetidines / Q000008:administration & dosage / Q000627:therapeutic use*; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D000069438:Ezetimibe; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007564:Japan; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D012107:Research Design; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional
chemical_list: D000924:Anticholesteremic Agents; D001384:Azetidines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D000069438:Ezetimibe
keywords: Atherosclerosis; Ezetimibe; Intravascular ultrasound; LDL-cholesterol; Non-obstructive coronary angioscopy