Yang Young-June, Lee Sang-Hak, Kim Byung Soo, Cho Yun-Kyeong, Cho Hyun-Jai, Cho Kyoung Im, Kim Seok-Yeon, Ryu Jae Kean, Cho Jin-Man, Park Joong-Il, Park Jong-Seon, Park Chang Gyu, Chun Woo Jung, Kim Myung-A, Jin Dong-Kyu, Lee Namho, Kim Byung Jin, Koh Kwang Kon, Suh Jon, Lee Seung-Hwan, Lee Byoung-Kwon, Oh Seung-Jin, Jin Han-Young, Ahn Youngkeun, Lee Sang-Gon, Bae Jang-Ho, Park Woo Jung, Lee Sang-Chol, Lee Han Cheol, Lee Jaewon, Park Cheolwon, Lee Backhwan, Jang Yangsoo
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.
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.
Clin Ther. 2017 Jan;39(1):107-117. doi: 10.1016/j.clinthera.2016.11.014. Epub 2016 Dec 19.
The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk.
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.
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.
Rosuvastatin/ezetimibe combination therapy has better efficacy and target achievement rates than rosuvastatin monotherapy in patients with high cardiovascular risk.
本研究旨在评估瑞舒伐他汀/依折麦布联合治疗对韩国心血管高危患者的疗效和耐受性。
这是一项为期12周的随机、双盲、安慰剂对照、多中心研究。共筛选了337例患者。经过4周的导入期后，根据美国国家胆固醇教育计划成人治疗小组III指南定义，将其中245例高危或中度高危患者随机分组。患者接受以下6种治疗方案中的一种，为期8周：（1）瑞舒伐他汀5毫克；（2）瑞舒伐他汀5毫克/依折麦布10毫克；（3）瑞舒伐他汀10毫克；（4）瑞舒伐他汀10毫克/依折麦布10毫克；（5）瑞舒伐他汀20毫克；或（6）瑞舒伐他汀20毫克/依折麦布10毫克。主要结局变量是药物治疗第8周时低密度脂蛋白胆固醇（LDL-C）水平的百分比变化。次要结局变量包括其他血脂变量的百分比变化以及LDL-C目标达成率。还进行了耐受性分析。
单药治疗组LDL-C的百分比变化范围为-45%至-56%（平均-51%），联合治疗组为-58%至-63%（平均-60%）。联合治疗合并组的百分比变化大于相应的单药治疗组（合并组P<0.001）；这种差异在他汀类药物剂量较低的治疗方案中更为明显。联合治疗组总胆固醇和甘油三酯的百分比降低幅度大于单药治疗组。单药治疗组LDL-C目标达成率为64%至87%（平均73%），联合治疗组为87%至95%（平均91%）（合并组P=0.01）。在较低剂量瑞舒伐他汀治疗时，接受联合治疗的患者的达标率显著高于单药治疗患者。各组间各种不良事件患者的比例无显著差异。
在心血管高危患者中，瑞舒伐他汀/依折麦布联合治疗比瑞舒伐他汀单药治疗具有更好的疗效和目标达成率。
