Illingworth D R, Crouse J R, Hunninghake D B, Davidson M H, Escobar I D, Stalenhoef A F, Paragh G, Ma P T, Liu M, Melino M R, O'Grady L, Mercuri M, Mitchel Y B
Division of Endocrinology, Diabetes, & Clinical Nutrition (L465), Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, Oregon 97201, USA.
Curr Med Res Opin. 2001;17(1):43-50.
At higher doses, simvastatin has been shown to produce significantly greater increases in high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I than atorvastatin. To extend and confirm these findings, a 36-week, randomized, double-blind, dose-titration study was performed in 826 hypercholesterolemic patients to compare the effects of simvastatin and atorvastatin on HDL cholesterol, apo A-I, and clinical and laboratory safety. PRIMARY HYPOTHESIS: Simvastatin, across a range of doses, will be more effective than atorvastatin at raising HDL cholesterol and apo A-I levels.
A total of 826 hypercholesterolemic patients were enrolled in this double-blind, randomized, parallel, 36-week, dose-escalation study. Patients randomized to simvastatin received 40 mg/day for the first 6 weeks, 80 mg/day for the next 6 weeks, and remained on 80 mg/day for the final 24 weeks. Patients randomized to atorvastatin received 20 mg/day for the first 6 weeks, 40 mg/day for the next 6 weeks, and 80 mg/day for the remaining 24 weeks.
During the first 12 weeks of the study, simvastatin increased HDL cholesterol and apo A-I more than the comparative doses of atorvastatin, while producing slightly lower reductions in low-density lipoprotein (LDL) cholesterol and triglycerides. At the maximal dose comparison, simvastatin 80 mg and atorvastatin 80 mg, the HDL cholesterol and apo A-I differences favoring simvastatin were larger than at the lower doses. In addition, at the maximal dose comparison, the incidence of drug-related clinical adverse experiences was approximately two-fold higher with atorvastatin 80 mg than with simvastatin 80 mg (23 versus 12%, p < 0.001), due predominantly to a greater incidence of gastrointestinal symptoms with atorvastatin (10 versus 3%, p < 0.001). The incidence of clinically significant alanine aminotransferase elevations was also higher with atorvastatin 80 mg than with simvastatin 80 mg (3.8 versus 0.5%, p < 0.010), especially in women (6.0 versus 0.6%).
At the doses compared in this study, simvastatin led to greater increases in HDL cholesterol and apo A-I levels than atorvastatin. At the maximum dose comparison, there were fewer drug-related gastrointestinal symptoms and clinically significant aminotransferase elevations with simvastatin.
已表明，与阿托伐他汀相比，更高剂量的辛伐他汀能显著更大程度地升高高密度脂蛋白（HDL）胆固醇和载脂蛋白（apo）A-I。为扩展并证实这些发现，对826例高胆固醇血症患者进行了一项为期36周的随机、双盲、剂量滴定研究，以比较辛伐他汀和阿托伐他汀对HDL胆固醇、apo A-I以及临床和实验室安全性的影响。主要假设：在一系列剂量范围内，辛伐他汀在升高HDL胆固醇和apo A-I水平方面比阿托伐他汀更有效。
总共826例高胆固醇血症患者参与了这项双盲、随机、平行、为期36周的剂量递增研究。随机分配至辛伐他汀组的患者在最初6周接受40mg/天，接下来6周接受80mg/天，并在最后24周维持80mg/天。随机分配至阿托伐他汀组的患者在最初6周接受20mg/天，接下来6周接受40mg/天，在剩余24周接受80mg/天。
在研究的前12周，与阿托伐他汀的对比剂量相比，辛伐他汀升高HDL胆固醇和apo A-I的幅度更大，同时低密度脂蛋白（LDL）胆固醇和甘油三酯的降低幅度略小。在最大剂量对比中，辛伐他汀80mg和阿托伐他汀80mg，有利于辛伐他汀的HDL胆固醇和apo A-I差异比低剂量时更大。此外，在最大剂量对比中，80mg阿托伐他汀的药物相关临床不良事件发生率比80mg辛伐他汀高约两倍（23%对12%，p<0.001），主要是因为阿托伐他汀的胃肠道症状发生率更高（10%对3%，p<0.001）。80mg阿托伐他汀的临床显著丙氨酸氨基转移酶升高发生率也比80mg辛伐他汀高（3.8%对0.5%，p<0.010），尤其是在女性中（6.0%对0.6%）。
在本研究比较的剂量下，辛伐他汀比阿托伐他汀能更大程度地升高HDL胆固醇和apo A-I水平。在最大剂量对比中，辛伐他汀的药物相关胃肠道症状和临床显著的转氨酶升高较少。
