Yi Yong Jin, Kim Hyo Jin, Jo Sang Kyung, Kim Sung Gyun, Song Young Rim, Chung Wookyung, Han Kum Hyun, Lee Chang Hwa, Hwang Young-Hwan, Oh Kook-Hwan
Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Internal Medicine, Korea University Medical College, Seoul, Republic of Korea.
Clin Ther. 2014 Aug 1;36(8):1182-90. doi: 10.1016/j.clinthera.2014.06.005. Epub 2014 Jul 2.
Evening administration of the conventional immediate-release (IR) formulation of simvastatin is recommended because of its short half-life (1.9 hours). In a healthy population, morning administration of a controlled-release (CR) formulation of simvastatin was shown to have equivalent lipid-lowering efficacy and a safety profile similar to that of evening doses of IR simvastatin. The present study aimed to verify noninferiority and to compare the safety of morning administration of CR simvastatin with that of evening administration of IR simvastatin in patients with chronic kidney disease (CKD) who have dyslipidemia.
The present study was a prospective, multicenter, double-blind, Phase IV trial with an active comparator. We randomly assigned 122 patients with CKD and dyslipidemia to 1 of 2 drug administration groups: morning administration of CR simvastatin 20 mg (test group) and evening administration of IR simvastatin 20 mg (control group). After 8 weeks, the treatment outcomes and adverse effects of the 2 treatments were compared.
The mean (SD) percentage of change in serum LDL-C at the end of treatment was -35.1% (15.7%) for the test group and -35.6% (14.6%) for the control group. The difference between the 2 groups was not significant (P = 0.858). The 95% CI of the difference in the percentage of change of LDL-C between the test and control groups was -6.0 to 5.0. There was no difference in the percentage of change of total cholesterol (-24.3% [12.5%] vs -26.5% [12.0%], P = 0.317), triglyceride (-10.6% [35.1%] vs -12.4% [33.2%], P = 0.575) and HDL-C (10.2% [20.7%] vs 4.5% [11.4%], P = 0.064). Treatment-related adverse events were similar in both groups (10 events in the test group vs 8 events in the control group, P = 0.691).
The efficacy of morning administration of CR simvastatin was noninferior to evening administration of IR simvastatin in patients with CKD. Furthermore, the safety profile analysis showed no significant difference between the 2 treatments. Morning administration of CR simvastatin is expected to increase patient compliance and therefore better control of dyslipidemia in CKD patients.
由于辛伐他汀传统速释（IR）制剂的半衰期较短（1.9小时），故推荐在晚上服用。在健康人群中，辛伐他汀控释（CR）制剂早晨给药显示出与晚上服用IR辛伐他汀等效的降脂疗效及相似的安全性。本研究旨在验证非劣效性，并比较慢性肾脏病（CKD）合并血脂异常患者早晨服用CR辛伐他汀与晚上服用IR辛伐他汀的安全性。
本研究是一项前瞻性、多中心、双盲、有活性对照的IV期试验。我们将122例CKD合并血脂异常患者随机分为2个给药组之一：早晨服用20mg CR辛伐他汀（试验组）和晚上服用20mg IR辛伐他汀（对照组）。8周后，比较两种治疗的疗效和不良反应。
治疗结束时，试验组血清低密度脂蛋白胆固醇（LDL-C）变化的平均（标准差）百分比为-35.1%（15.7%），对照组为-35.6%（14.6%）。两组间差异无统计学意义（P = 0.858）。试验组与对照组LDL-C变化百分比差异的95%置信区间为-6.0至5.0。总胆固醇变化百分比（-24.3% [12.5%] 对 -26.5% [12.0%]，P = 0.317）、甘油三酯变化百分比（-10.6% [35.1%] 对 -12.4% [33.2%]，P = 0.575）和高密度脂蛋白胆固醇（HDL-C）变化百分比（10.2% [20.7%] 对 4.5% [11.4%]，P = 0.064）均无差异。两组治疗相关不良事件相似（试验组10例，对照组8例，P = 0.691）。
CKD患者早晨服用CR辛伐他汀的疗效不劣于晚上服用IR辛伐他汀。此外，安全性分析显示两种治疗间无显著差异。早晨服用CR辛伐他汀有望提高患者依从性，从而更好地控制CKD患者的血脂异常。
