Soon Jun Hong1, Han Saem Jeong1, Jeong Cheon Ahn2, Dong-Hun Cha3, Kyung Heon Won4, Weon Kim5, Sang Kyoon Cho6, Seok-Yeon Kim4, Byung-Su Yoo7, Ki Chul Sung8, Seung-Woon Rha9, Joon-Han Shin10, Kyoo Rok Han11, Wook Sung Chung12, Min Su Hyon13, Han Cheol Lee14, Jang-Ho Bae15, Moo-Yong Rhee16, Jun Kwan17, Dong Woon Jeon18, Ki Dong Yoo19, Hyo-Soo Kim20. 1. Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea. 2. Division of Cardiology, Department of Internal Medicine, Korea University Ansan Hospital, Ansan, Republic of Korea. 3. Division of Cardiology, Department of Internal Medicine, Bundang CHA Hospital, CHA University College of Medicine, Seongnam, Republic of Korea. 4. Division of Cardiology, Department of Internal Medicine, Seoul Medical Center, Seoul, Republic of Korea. 5. Cardiovascular Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea. 6. Division of Cardiology, Department of Internal Medicine, Bundang Jesaeng Hospital, Seongnam, Republic of Korea. 7. Division of Cardiology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea. 8. Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. 9. Cardiovascular Center, Korea University Guro Hospital, Seoul, Republic of Korea. 10. Department of Cardiology, Ajou University Medical Center, Suwon, Republic of Korea. 11. Division of Cardiology, Department of Internal Medicine, Kangdong Sacred Heart Hospital, College of Medicine, Hallym University, Seoul, Republic of Korea. 12. Division of Cardiology, Department of Internal Medicine, The Catholic University, Seoul, Republic of Korea. 13. Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Hospital, Seoul, Republic of Korea. 14. Division of Cardiology, Department of Internal Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Republic of Korea. 15. Division of Cardiology Heart Center, Konyang University Hospital, Daejeon. 16. Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, Republic of Korea. 17. Division of Cardiology, Department of Internal Medicine, Inha University Hospital, Incheon, Republic of Korea. 18. Division of Cardiology, Department of Internal Medicine, NHIS Ilsan Hospital, Goyang, Republic of Korea. 19. Division of Cardiology, Department of Internal Medicine, The Catholic University of Korea St. Vincent's Hospital, Suwon, Republic of Korea. 20. 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.
Abstract
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.
RCT Entities:
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.
Authors: Fadia Tohme Shaya; Krystal Sing; Robert Milam; Fasahath Husain; Michael A Del Aguila; Miraj Y Patel Journal: Am J Cardiovasc Drugs Date: 2020-06 Impact factor: 3.571