Catapano Alberico L, Davidson Michael H, Ballantyne Christie M, Brady William E, Gazzara Russell A, Tomassini Joanne E, Tershakovec Andrew M
University of Milan, Milan, Italy.
Curr Med Res Opin. 2006 Oct;22(10):2041-53. doi: 10.1185/030079906X132721.
To assess the lipid-altering efficacy and safety of ezetimibe/simvastatin single tablet product compared with rosuvastatin at the approved usual starting, next highest, and maximum doses.
Double-blind, multicenter, 6-week, parallel-group study in hypercholesterolemic patients (n = 2959). Patients were randomized based on stratification by low-density lipoprotein cholesterol (LDL-C) levels to ezetimibe/simvastatin or rosuvastatin, respectively, at the usual starting (10/20 or 10 mg/day), the next highest (10/40 or 20 mg/day), and maximum doses (10/80 or 40 mg/day).
At all doses and across doses, ezetimibe/simvastatin reduced LDL-C levels significantly more (52-61%) than rosuvastatin (46-57%; p < or = 0.001). Significantly greater percentages of all patients (p < 0.001) and high risk patients (p < or = 0.005) attained LDL-C levels < 70 mg/dL (1.8 mmol/L) following ezetimibe/simvastatin treatment compared with rosuvastatin at the prespecified doses and across doses. Ezetimibe/simvastatin also produced significantly greater reductions in total cholesterol (p < 0.001), non-high-density lipoprotein cholesterol (p < 0.001), lipid ratios (p < or = 0.003), and apolipoprotein B (p < 0.05). Reductions in triglycerides were significantly greater with ezetimibe/simvastatin than rosuvastatin at the usual starting (p = 0.004) and next highest (p = 0.006) doses, and across all doses (p < 0.001). Increases in high-density lipoprotein cholesterol, and decreases in high sensitivity C reactive protein (hsCRP) were similar between treatment groups. Safety profiles were comparable for both treatments; however, the percent of patients with proteinuria was significantly higher following rosuvastatin treatment than ezetimibe/simvastatin, respectively at 10 mg versus 10/20 mg/day (p = 0.004) and 40 mg versus 10/80 mg/day (p < 0.001).
Ezetimibe/simvastatin was more effective than rosuvastatin in LDL-C lowering, and provided greater or comparable improvements in other lipid measures and hsCRP at the approved usual starting, next highest, and maximum doses in hypercholesterolemic patients. Although the doses compared in this study were not equivalent on a milligram basis, the results provide clinically relevant information regarding the use of these drugs for initial therapy and for subsequent use at higher doses when appropriate. Both treatments were generally well-tolerated; however, this study was not powered nor of sufficient duration to assess the prevalence of rare clinical adverse effects. Overall, ezetimibe/simvastatin offers an effective and tolerable treatment option for lipid management. An assessment of its full clinical benefit awaits evaluation in longer-term clinical studies.
评估依折麦布/辛伐他汀单片制剂与瑞舒伐他汀在批准的常用起始剂量、次高剂量和最大剂量下的调脂疗效及安全性。
对2959例高胆固醇血症患者进行双盲、多中心、为期6周的平行组研究。患者根据低密度脂蛋白胆固醇（LDL-C）水平分层，分别随机接受依折麦布/辛伐他汀或瑞舒伐他汀治疗，剂量分别为常用起始剂量（10/20或10毫克/天）、次高剂量（10/40或20毫克/天）和最大剂量（10/80或40毫克/天）。
在所有剂量及各剂量组中，依折麦布/辛伐他汀降低LDL-C水平的幅度（52 - 61%）均显著大于瑞舒伐他汀（46 - 57%；p≤0.001）。与瑞舒伐他汀在预设剂量及各剂量组相比，接受依折麦布/辛伐他汀治疗的所有患者（p < 0.001）及高危患者（p≤0.005）达到LDL-C水平<70毫克/分升（1.8毫摩尔/升）的百分比显著更高。依折麦布/辛伐他汀还能显著更大幅度地降低总胆固醇（p < 0.001）、非高密度脂蛋白胆固醇（p < 0.001）、脂质比率（p≤0.003）和载脂蛋白B（p < 0.05）。在常用起始剂量（p = 0.004）、次高剂量（p = 0.006）及所有剂量组（p < 0.001）中，依折麦布/辛伐他汀降低甘油三酯的幅度均显著大于瑞舒伐他汀。治疗组间高密度脂蛋白胆固醇的升高及高敏C反应蛋白（hsCRP）的降低相似。两种治疗的安全性相当；然而，瑞舒伐他汀治疗后蛋白尿患者的百分比显著高于依折麦布/辛伐他汀，分别为10毫克/天与10/20毫克/天（p = 0.004）以及40毫克/天与10/80毫克/天（p < 0.001）。
在高胆固醇血症患者中，依折麦布/辛伐他汀在降低LDL-C方面比瑞舒伐他汀更有效，并且在批准的常用起始剂量、次高剂量和最大剂量下，在其他血脂指标及hsCRP方面提供了更大或相当的改善。尽管本研究中比较的剂量在毫克基础上并不等效，但结果提供了关于这些药物用于初始治疗以及在适当情况下后续使用更高剂量的临床相关信息。两种治疗总体耐受性良好；然而，本研究没有足够的样本量和时长来评估罕见临床不良反应的发生率。总体而言，依折麦布/辛伐他汀为血脂管理提供了一种有效且可耐受的治疗选择。其全面临床益处的评估有待在长期临床研究中进行。
