Davidson Michael H, Ose Leiv, Frohlich Jiri, Scott Russell S, Dujovne Carlos A, Escobar Ivan D, Bertolami Marcelo C, Cihon Frank, Maccubbin Darbie L, Mercuri Michele
Chicago Center for Clinical Research, Chicago, Illinois 60610, USA.
Clin Cardiol. 2003 Nov;26(11):509-14. doi: 10.1002/clc.4960261106.
In addition to lowering plasma levels of low-density lipoprotein cholesterol (LDL-C), statins also raise high-density lipoprotein cholesterol (HDL-C).
Recent studies have shown that treatment with simvastatin results in larger increases in HDL-C than those seen with atorvastatin. The results of three clinical studies are analyzed, comparing the effects of simvastatin and atorvastatin on HDL-C and apolipoprotein A-I (apo A-I) in the total cohort and in several subgroups of hypercholesterolemic patients. The three studies were all multicenter, randomized clinical trials that included simvastatin (20-80 mg) and atorvastatin (10-80 mg) treatment arms. The subgroup analyses performed were gender; age (< 65 and > or = 65 years); baseline HDL-C (male: < 40 or > or = 40 mg/dl; female: < 45 or > or = 45 mg/dl), baseline LDL-C (< 160 or > or = 160 mg/dl), and baseline triglycerides (< 200 or > or = 200 mg/dl).
Both drugs produced similar increases in HDL-C levels at low doses; however, at higher drug doses (40 and 80 mg), HDL-C showed a significantly greater increase with simvastatin than with atorvastatin (p < 0.05 to < 0.001). Therefore, while HDL-C remained consistently elevated across all doses of simvastatin, there appeared to be a pattern of decreasing HDL-C with an increasing dose of atorvastatin. A similar negative dose response pattern was also observed with apo A-I in atorvastatin-treated patients, suggesting a reduction in the number of circulating HDL particles at higher doses. Both drugs reduced LDL-C and triglycerides in a dose-dependent fashion, with atorvastatin showing slightly greater effects. The differential effects of atorvastatin and simvastatin on HDL-C and apo A-I were observed for both the whole study cohorts and all subgroups examined; thus, no consistent treatment-by-subgroup interactions were observed.
The data presented show that, across different hypercholesterolemic patient subgroups, simvastatin increases HDL-C and apo A-I more than atorvastatin at higher doses, with evidence of a negative dose response effect on HDL-C and apo A-I with atorvastatin, but not simvastatin.
除了降低血浆低密度脂蛋白胆固醇（LDL-C）水平外，他汀类药物还能提高高密度脂蛋白胆固醇（HDL-C）水平。
最近的研究表明，与阿托伐他汀相比，辛伐他汀治疗能使HDL-C有更大幅度的升高。分析了三项临床研究的结果，比较了辛伐他汀和阿托伐他汀对总队列以及高胆固醇血症患者几个亚组中HDL-C和载脂蛋白A-I（apo A-I）的影响。这三项研究均为多中心随机临床试验，包括辛伐他汀（20 - 80毫克）和阿托伐他汀（10 - 80毫克）治疗组。所进行的亚组分析包括性别；年龄（<65岁和≥65岁）；基线HDL-C（男性：<40或≥40毫克/分升；女性：<45或≥45毫克/分升）、基线LDL-C（<160或≥160毫克/分升）以及基线甘油三酯（<200或≥200毫克/分升）。
两种药物在低剂量时使HDL-C水平升高的幅度相似；然而，在较高药物剂量（40和80毫克）时，辛伐他汀使HDL-C升高的幅度显著大于阿托伐他汀（p<0.05至<0.001）。因此，虽然辛伐他汀所有剂量下HDL-C均持续升高，但阿托伐他汀似乎呈现出随着剂量增加HDL-C降低的趋势。在接受阿托伐他汀治疗的患者中，apo A-I也观察到类似的负剂量反应模式，表明高剂量时循环HDL颗粒数量减少。两种药物均以剂量依赖方式降低LDL-C和甘油三酯，阿托伐他汀的效果略强。在整个研究队列和所有检查的亚组中均观察到阿托伐他汀和辛伐他汀对HDL-C和apo A-I的不同影响；因此，未观察到一致的亚组与治疗的相互作用。
所呈现的数据表明，在不同的高胆固醇血症患者亚组中，高剂量时辛伐他汀比阿托伐他汀更能提高HDL-C和apo A-I水平，有证据表明阿托伐他汀对HDL-C和apo A-I有负剂量反应效应，而辛伐他汀则没有。
