Takafumi Hiro1, Atsushi Hirayama2, Yasunori Ueda3, Sei Komatsu4, Hiroshi Matsuoka5, Tadateru Takayama2, Masaharu Ishihara6, Takatoshi Hayashi7, Satoshi Saito8, Kazuhisa Kodama9. 1. Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. Electronic address: hiro.takafumi@nihon-u.ac.jp. 2. Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan. 3. Cardiovascular Division, Osaka Police Hospital, Osaka, Japan. 4. Cardiovascular Center, Amagasaki Central Hospital, Amagasaki, Japan. 5. Department of Cardiovascular Medicine, Ehime Prefectural Imabari Hospital, Imabari, Japan. 6. Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center Hospital, Suita, Japan. 7. Hyogo Prefectural Awaji Medical Center, Sumoto, Japan. 8. Division of Cardiovascular Medicine, Keiai Hospital, Tokyo, Japan. 9. Cardiovascular Center, Amagasaki Central Hospital, Amagasaki, Japan; Second Research Team, J-MIC Committee, Japan Health Promotion Foundation, Tokyo, Japan.
Abstract
BACKGROUND AND PURPOSE: 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.
RCT Entities:
BACKGROUND AND PURPOSE: 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.