Young-June Yang1, Sang-Hak Lee2, Byung Soo Kim3, Yun-Kyeong Cho4, Hyun-Jai Cho5, Kyoung Im Cho6, Seok-Yeon Kim7, Jae Kean Ryu8, Jin-Man Cho9, Joong-Il Park10, Jong-Seon Park11, Chang Gyu Park12, Woo Jung Chun13, Myung-A Kim14, Dong-Kyu Jin15, Namho Lee16, Byung Jin Kim17, Kwang Kon Koh18, Jon Suh19, Seung-Hwan Lee20, Byoung-Kwon Lee21, Seung-Jin Oh22, Han-Young Jin23, Youngkeun Ahn24, Sang-Gon Lee25, Jang-Ho Bae26, Woo Jung Park27, Sang-Chol Lee28, Han Cheol Lee29, Jaewon Lee30, Cheolwon Park30, Backhwan Lee30, Yangsoo Jang31. 1. Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. 2. Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. Electronic address: shl1106@yuhs.ac. 3. Division of Cardiology, Department of Internal Medicine, Daedong Hospital, Busan, Korea. 4. Division of Cardiology, Keimyung University Dongsan Medical Center, Daegu, Korea. 5. Cardiovascular Center and Cardiovascular Research Institute, Seoul National University College of Medicine, Seoul, Korea. 6. Division of Cardiology, Department of Internal Medicine, Cardiovascular Research Institute, Kosin University School of Medicine, Busan, Korea. 7. Department of Cardiology, Seoul Medical Center, Seoul, Korea. 8. Department of Cardiology, Daegu Catholic University Medical Center, Daegu, Korea. 9. Department of Cardiology, Kyunghee University East-West Neo Medical Center, Seoul, Korea. 10. Division of Cardiology, Department of Internal Medicine, Veterans Health Service Medical Center, Seoul, Korea. 11. Department of Medicine, Yeungnam University Medical Center, Daegu, Korea. 12. Department of Cardiology, Korea University Guro Hospital, Seoul, Korea. 13. Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea. 14. Division of Cardiology, Department of Internal Medicine, SMG-SNU Seoul Boramae Hospital, Seoul, Korea. 15. Division of Cardiology, Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Korea. 16. Cardiology Division, Kangnam Sacred Heart Hospital, Hallym University Medical Center, Seoul, Korea. 17. Division of Cardiology, Department of Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea. 18. Department of Cardiology, Gachon University Gil Medical Center, Incheon, Korea. 19. Department of Cardiology, Soonchunhyang University Hospital Bucheon, Bucheon, Korea. 20. Division of Cardiology, Wonju College of Medicine, Yonsei University, Wonju, Korea. 21. Division of Cardiology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. 22. Division of Cardiology, Department of Internal Medicine, NHIS Ilsan Hospital, Goyang, Korea. 23. Division of Cardiology, Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea. 24. Department of Cardiology, Heart Research Center of Chonnam National University, Gwangju, Korea. 25. Department of Cardiology, Ulsan University College of Medicine, Ulsan, Korea. 26. Division of Cardiology, Department of Internal Medicine, Konyang University Hospital, Daejeon, Korea. 27. Division of Cardiology, Department of Internal Medicine, Hallym University Medical Center, Anyang, Korea. 28. Division of Cardiology, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 29. Division of Cardiology, Department of Internal Medicine, Pusan National University School of Medicine, Medical Research Institute, Pusan National University Hospital, Busan, Korea. 30. Research & Development Division, Alvogen Korea Co., Ltd., Seoul, Korea. 31. Division of Cardiology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea; Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. Electronic address: jangys1212@yuhs.ac.
Abstract
PURPOSE: The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk. METHODS: This was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 337 patients were screened. After a 4-week run-in period, 245 of these patients with high or moderately high risk as defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines were randomly assigned. Patients received 1 of 6 regimens for 8 weeks as follows: (1) rosuvastatin 5 mg, (2) rosuvastatin 5 mg/ezetimibe 10 mg, (3) rosuvastatin 10 mg, (4) rosuvastatin 10 mg/ezetimibe 10 mg, (5) rosuvastatin 20 mg, or (6) rosuvastatin 20 mg/ezetimibe 10 mg. The primary outcome variable was percentage change in the level of LDL-C at week 8 of drug treatment. Secondary outcome variables included percentage changes of other lipid variables and achievement rates of LDL-C targets. Tolerability analyses were also performed. FINDINGS: The percentage change of LDL-C ranged from -45% to -56% (mean, -51%) in the monotherapy groups and from -58% to -63% (mean, -60%) in the combination therapy groups. The percentage change was greater in the pooled combination therapy group than in the counterpart (P < 0.001 for the pooled groups); this difference was more obvious for regimens with a lower statin dose. The percentage reductions of total cholesterol and triglycerides were greater in the combination groups than in the monotherapy groups. The LDL-C target achievement rates were 64% to 87% (mean, 73%) in the monotherapy groups and 87% to 95% (mean, 91%) in the combination groups (P = 0.01 for the pooled groups). The rates were significantly greater in patients receiving the combination therapy than in the monotherapy at lower doses of rosuvastatin. The proportions of patients with various adverse events were not significantly different between the groups. IMPLICATIONS: Rosuvastatin/ezetimibe combination therapy has better efficacy and target achievement rates than rosuvastatin monotherapy in patients with high cardiovascular risk.
RCT Entities:
PURPOSE: The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk. METHODS: This was a 12-week, randomized, double-blind, placebo-controlled, multicenter study. A total of 337 patients were screened. After a 4-week run-in period, 245 of these patients with high or moderately high risk as defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines were randomly assigned. Patients received 1 of 6 regimens for 8 weeks as follows: (1) rosuvastatin 5 mg, (2) rosuvastatin 5 mg/ezetimibe 10 mg, (3) rosuvastatin 10 mg, (4) rosuvastatin 10 mg/ezetimibe 10 mg, (5) rosuvastatin 20 mg, or (6) rosuvastatin 20 mg/ezetimibe 10 mg. The primary outcome variable was percentage change in the level of LDL-C at week 8 of drug treatment. Secondary outcome variables included percentage changes of other lipid variables and achievement rates of LDL-C targets. Tolerability analyses were also performed. FINDINGS: The percentage change of LDL-C ranged from -45% to -56% (mean, -51%) in the monotherapy groups and from -58% to -63% (mean, -60%) in the combination therapy groups. The percentage change was greater in the pooled combination therapy group than in the counterpart (P < 0.001 for the pooled groups); this difference was more obvious for regimens with a lower statin dose. The percentage reductions of total cholesterol and triglycerides were greater in the combination groups than in the monotherapy groups. The LDL-C target achievement rates were 64% to 87% (mean, 73%) in the monotherapy groups and 87% to 95% (mean, 91%) in the combination groups (P = 0.01 for the pooled groups). The rates were significantly greater in patients receiving the combination therapy than in the monotherapy at lower doses of rosuvastatin. The proportions of patients with various adverse events were not significantly different between the groups. IMPLICATIONS: Rosuvastatin/ezetimibe combination therapy has better efficacy and target achievement rates than rosuvastatin monotherapy in patients with high cardiovascular risk.