Dujovne Carlos A, Ettinger Mark P, McNeer J Frederick, Lipka Leslie J, LeBeaut Alexandre P, Suresh Ramachandran, Yang Bo, Veltri Enrico P
Kansas Foundation for Clinical Pharmacology, Radiant Research-Kansas City, 12200 W. 106th Street, Suite 330, Overland Park, KS 66215, USA.
Am J Cardiol. 2002 Nov 15;90(10):1092-7. doi: 10.1016/s0002-9149(02)02798-4.
The efficacy and safety of ezetimibe, a new cholesterol absorption inhibitor, was evaluated in this randomized, double-blind, placebo-controlled trial of 892 patients with primary hypercholesterolemia. After > or =2 weeks on the National Cholesterol Education Program (NCEP) Step I or a stricter diet and a 4- to 8-week single-blind placebo lead-in, patients with low-density lipoprotein (LDL) cholesterol 130 to 250 mg/dl and triglycerides < or =350 mg/dl were randomized 3:1 to receive ezetimibe 10 mg or placebo orally each morning for 12 weeks. The primary efficacy end point was the percent reduction in direct plasma LDL cholesterol from baseline to end point. A total of 434 men and 458 women (ages 18 to 85 years) received randomized treatment (666 ezetimibe 10 mg, 226 placebo). Demographics and baseline characteristics were similar between treatment groups. Ezetimibe significantly reduced direct LDL cholesterol by a mean of 16.9%, compared with an increase of 0.4% with placebo (p <0.01). Subgroup analysis indicated that response to ezetimibe was generally consistent across all subgroups, regardless of risk-factor status, gender, age, race, or baseline lipid profile. Ezetimibe effects on LDL cholesterol occurred early (2 weeks) and persisted throughout the 12-week treatment period. Compared with placebo, ezetimibe 10 mg also significantly improved calculated LDL cholesterol, apolipoprotein B, total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, and HDL(3) cholesterol (p <0.01). Ezetimibe was well tolerated. There were no differences in laboratory or clinical safety parameters, or gastrointestinal, liver, or muscle side effects from that of placebo. Ezetimibe 10 mg/day is well tolerated, reduces LDL cholesterol approximately 17%, and improves other key lipid parameters.
在这项针对892例原发性高胆固醇血症患者的随机、双盲、安慰剂对照试验中，对新型胆固醇吸收抑制剂依折麦布的疗效和安全性进行了评估。在遵循美国国家胆固醇教育计划（NCEP）第一步或更严格饮食方案≥2周以及4至8周的单盲安慰剂导入期后，将低密度脂蛋白（LDL）胆固醇水平为130至250mg/dl且甘油三酯≤350mg/dl的患者按3:1随机分组，分别每日早晨口服依折麦布10mg或安慰剂，为期12周。主要疗效终点是直接血浆LDL胆固醇从基线至终点的降低百分比。共有434名男性和458名女性（年龄18至85岁）接受随机治疗（666例接受依折麦布10mg，226例接受安慰剂）。各治疗组的人口统计学和基线特征相似。依折麦布使直接LDL胆固醇平均显著降低16.9%，而安慰剂组则升高了0.4%（p<0.01）。亚组分析表明，无论危险因素状态、性别、年龄、种族或基线血脂水平如何，依折麦布在所有亚组中的反应总体一致。依折麦布对LDL胆固醇的作用在早期（2周）即出现，并在整个12周治疗期持续存在。与安慰剂相比，10mg依折麦布还显著改善了计算得出的LDL胆固醇、载脂蛋白B、总胆固醇、甘油三酯、高密度脂蛋白（HDL）胆固醇和HDL(3)胆固醇（p<0.01）。依折麦布耐受性良好。实验室或临床安全性参数以及胃肠道、肝脏或肌肉副作用与安慰剂组无差异。每日10mg依折麦布耐受性良好，可使LDL胆固醇降低约17%，并改善其他关键血脂参数。
