PMID- 29402522 OWN - NLM STAT- MEDLINE DCOM- 20190226 LR - 20220318 IS - 1879-114X (Electronic) IS - 0149-2918 (Linking) VI - 40 IP - 2 DP - 2018 Feb TI - A Phase III, Multicenter, Randomized, Double-blind, Active Comparator Clinical Trial to Compare the Efficacy and Safety of Combination Therapy With Ezetimibe and Rosuvastatin Versus Rosuvastatin Monotherapy in Patients With Hypercholesterolemia: I-ROSETTE (Ildong Rosuvastatin & Ezetimibe for Hypercholesterolemia) Randomized Controlled Trial. PG - 226-241.e4 LID - S0149-2918(18)30007-9 [pii] LID - 10.1016/j.clinthera.2017.12.018 [doi] AB - PURPOSE: Combination therapy with ezetimibe and statins is recommended in cases of statin intolerance or insufficiency. The objective of this study was to compare the efficacy and safety of combination therapy with ezetimibe and rosuvastatin versus those of rosuvastatin monotherapy in patients with hypercholesterolemia. METHODS: I-ROSETTE (Ildong ROSuvastatin & ezETimibe for hypercholesTElolemia) was an 8-week, double-blind, multicenter, Phase III randomized controlled trial conducted at 20 hospitals in the Republic of Korea. Patients with hypercholesterolemia who required medical treatment according to National Cholesterol Education Program Adult Treatment Panel III guidelines were eligible for participation in the study. Patients were randomly assigned to receive ezetimibe 10 mg/rosuvastatin 20 mg, ezetimibe 10 mg/rosuvastatin 10 mg, ezetimibe 10 mg/rosuvastatin 5 mg, rosuvastatin 20 mg, rosuvastatin 10 mg, or rosuvastatin 5 mg in a 1:1:1:1:1:1 ratio. The primary end point was the difference in the mean percent change from baseline in LDL-C level after 8 weeks of treatment between the ezetimibe/rosuvastatin and rosuvastatin treatment groups. All patients were assessed for adverse events (AEs), clinical laboratory data, and vital signs. FINDINGS: Of 396 patients, 389 with efficacy data were analyzed. Baseline characteristics among 6 groups were similar. After 8 weeks of double-blind treatment, the percent changes in adjusted mean LDL-C levels at week 8 compared with baseline values were -57.0% (2.1%) and -44.4% (2.1%) in the total ezetimibe/rosuvastatin and total rosuvastatin groups, respectively (P < 0.001). The LDL-C-lowering efficacy of each of the ezetimibe/rosuvastatin combinations was superior to that of each of the respective doses of rosuvastatin. The mean percent change in LDL-C level in all ezetimibe/rosuvastatin combination groups was >50%. The number of patients who achieved target LDL-C levels at week 8 was significantly greater in the ezetimibe/rosuvastatin group (180 [92.3%] of 195 patients) than in the rosuvastatin monotherapy group (155 [79.9%] of 194 patients) (P < 0.001). There were no significant differences in the incidence of overall AEs, adverse drug reactions, and serious AEs; laboratory findings, including liver function test results and creatinine kinase levels, were comparable between groups. IMPLICATIONS: Fixed-dose combinations of ezetimibe/rosuvastatin significantly improved lipid profiles in patients with hypercholesterolemia compared with rosuvastatin monotherapy. All groups treated with rosuvastatin and ezetimibe reported a decrease in mean LDL-C level >50%. The safety and tolerability of ezetimibe/rosuvastatin therapy were comparable with those of rosuvastatin monotherapy. ClinicalTrials.gov identifier: NCT02749994. CI - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Hong, Soon Jun AU - Hong SJ AD - Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea. FAU - Jeong, Han Saem AU - Jeong HS AD - Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea. FAU - Ahn, Jeong Cheon AU - Ahn JC AD - Division of Cardiology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea. FAU - Cha, Dong-Hun AU - Cha DH AD - Division of Cardiology, Department of Internal Medicine, Bundang CHA Hospital, CHA University College of Medicine, Seongnam, Republic of Korea. FAU - Won, Kyung Heon AU - Won KH AD - Division of Cardiology, Department of Internal Medicine, Seoul Medical Center, Seoul, Republic of Korea. FAU - Kim, Weon AU - Kim W AD - Cardiovascular Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea. FAU - Cho, Sang Kyoon AU - Cho SK AD - Division of Cardiology, Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Republic of Korea. FAU - Kim, Seok-Yeon AU - Kim SY AD - Division of Cardiology, Department of Internal Medicine, Seoul Medical Center, Seoul, Republic of Korea. FAU - Yoo, Byung-Su AU - Yoo BS AD - Division of Cardiology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. FAU - Sung, Ki Chul AU - Sung KC AD - Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. FAU - Rha, Seung-Woon AU - Rha SW AD - Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea. FAU - Shin, Joon-Han AU - Shin JH AD - Department of Cardiology, Ajou University Medical Center, Suwon, Republic of Korea. FAU - Han, Kyoo Rok AU - Han KR AD - Division of Cardiology, Department of Internal Medicine, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Republic of Korea. FAU - Chung, Wook Sung AU - Chung WS AD - Division of Cardiology, Department of Internal Medicine, The Catholic University, Seoul, Republic of Korea. FAU - Hyon, Min Su AU - Hyon MS AD - Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Hospital, Seoul, Republic of Korea. FAU - Lee, Han Cheol AU - Lee HC AD - Division of Cardiology, Department of Internal Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. FAU - Bae, Jang-Ho AU - Bae JH AD - Division of Cardiology Heart Center, Konyang University Hospital, Daejeon. FAU - Rhee, Moo-Yong AU - Rhee MY AD - Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, Republic of Korea. FAU - Kwan, Jun AU - Kwan J AD - Division of Cardiology, Department of Internal Medicine, Inha University Hospital, Incheon, Republic of Korea. FAU - Jeon, Dong Woon AU - Jeon DW AD - Division of Cardiology, Department of Internal Medicine, NHIS Ilsan Hospital, Goyang, Republic of Korea. FAU - Yoo, Ki Dong AU - Yoo KD AD - Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea St. Vincent's Hospital, Suwon, Republic of Korea. FAU - Kim, Hyo-Soo AU - Kim HS AD - Division of Cardiology, Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: usahyosoo@gmail.com. LA - eng SI - ClinicalTrials.gov/NCT02749994 PT - Clinical Trial, Phase III PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PL - United States TA - Clin Ther JT - Clinical therapeutics JID - 7706726 RN - 0 (Anticholesteremic Agents) RN - 0 (Cholesterol, LDL) RN - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors) RN - 83MVU38M7Q (Rosuvastatin Calcium) RN - EOR26LQQ24 (Ezetimibe) SB - IM MH - Aged MH - Anticholesteremic Agents/*administration & dosage/therapeutic use MH - Cholesterol, LDL/blood MH - Double-Blind Method MH - Drug Therapy, Combination MH - Ezetimibe/*administration & dosage/therapeutic use MH - Female MH - Humans MH - Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage/therapeutic use MH - Hypercholesterolemia/*drug therapy MH - Male MH - Middle Aged MH - Republic of Korea MH - Rosuvastatin Calcium/*administration & dosage MH - Treatment Outcome OTO - NOTNLM OT - ezetimibe OT - hypercholesterolemia OT - rosuvastatin OT - singe-pill combination EDAT- 2018/02/07 06:00 MHDA- 2019/02/27 06:00 CRDT- 2018/02/07 06:00 PHST- 2017/09/16 00:00 [received] PHST- 2017/11/16 00:00 [revised] PHST- 2017/12/22 00:00 [accepted] PHST- 2018/02/07 06:00 [pubmed] PHST- 2019/02/27 06:00 [medline] PHST- 2018/02/07 06:00 [entrez] AID - S0149-2918(18)30007-9 [pii] AID - 10.1016/j.clinthera.2017.12.018 [doi] PST - ppublish SO - Clin Ther. 2018 Feb;40(2):226-241.e4. doi: 10.1016/j.clinthera.2017.12.018.