一种新型HMG-CoA还原酶抑制剂阿托伐他汀在高甘油三酯血症患者中的疗效与安全性。

Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia.

作者信息

Bakker-Arkema R G, Davidson M H, Goldstein R J, Davignon J, Isaacsohn J L, Weiss S R, Keilson L M, Brown W V, Miller V T, Shurzinske L J, Black D M

机构信息

Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co, Ann Arbor, Mich 48105-1047, USA.

出版信息

JAMA. 1996 Jan 10;275(2):128-33.

PMID:8531308

Abstract

OBJECTIVE

To assess the lipid-lowering effect of atorvastatin (a new 3-hydroxy-3-methylglutaryl coenzyme A [HMG-CoA] reductase inhibitor) on levels of serum triglycerides and other lipoprotein fractions in patients with primary hypertriglyceridemia, determine if atorvastatin causes a redistribution of triglycerides in various lipoprotein fractions, and assess its safety by reporting adverse events and clinical laboratory measurements.

DESIGN

Randomized double-blind, placebo-controlled, parallel-group, multicenter trial.

SETTING

Community- and university-based research centers.

PATIENTS

A total of 56 patients (aged 26 to 74 years) with a mean baseline triglyceride level of 6.80 mmol/L (603.3 mg/dL) and a mean baseline low-density lipoprotein cholesterol (LDL-C) level of 3.07 mmol/L (118.7 mg/dL).

INTERVENTIONS

Cholesterol-lowering diet (National Institutes of Health National Cholesterol Education Program Step I Diet) and either 5 mg, 20 mg, or 80 mg of atorvastatin, or placebo.

MAIN OUTCOME MEASURES

Percent change from baseline in total triglycerides for three dose levels of atorvastatin compared with placebo.

RESULTS

Mean reductions in total triglycerides between 5 mg, 20 mg, and 80 mg of atorvastatin and placebo after 4 weeks of treatment were -26.5%, -32.4%, -45.8%, and -8.9%, respectively. Mean reductions in LDL-C were -16.7%, -33.2%, -41.4%, and -1.4%, respectively, and very low-density lipoprotein cholesterol (VLDL-C) were -34.3%, -45.9%, -57.7%, and -5.5%, respectively. Similar mean changes in total apolipoprotein B (apo B) (-16.9%, -32.8%, -41.7%, and +1.0%), apo B in LDL (-14.8%, -29.8%, -42.0%, and -3.1%), and apo B in VLDL (-23.8%, -35.8%, -34.4%, and +11.7%) were observed. In addition, comparable mean changes in LDL triglycerides (-22.5%, -30.7%, -39.9%, and +3.9%) and VLDL triglycerides (-28.1%, -34.0%, -47.3%, and -10.8%) were seen.

CONCLUSIONS

In atorvastatin treatment groups, total serum triglyceride levels decreased in a dose-dependent manner, reductions in the 20-mg and 80-mg groups were statistically significant (P < .05) compared with placebo. Atorvastatin did not cause a redistribution of triglycerides but consistently lowered triglycerides in all lipoprotein fractions. Atorvastatin was well tolerated.

摘要

目的

评估阿托伐他汀（一种新型3-羟基-3-甲基戊二酰辅酶A [HMG-CoA]还原酶抑制剂）对原发性高甘油三酯血症患者血清甘油三酯水平及其他脂蛋白组分的降脂作用，确定阿托伐他汀是否会导致甘油三酯在不同脂蛋白组分中的重新分布，并通过报告不良事件和临床实验室检测评估其安全性。

设计

随机双盲、安慰剂对照、平行组、多中心试验。

地点

社区及大学研究中心。

患者

共56例患者（年龄26至74岁），平均基线甘油三酯水平为6.80 mmol/L（603.3 mg/dL），平均基线低密度脂蛋白胆固醇（LDL-C）水平为3.07 mmol/L（118.7 mg/dL）。

干预措施

降胆固醇饮食（美国国立卫生研究院国家胆固醇教育计划第一步饮食），以及5 mg、20 mg或80 mg阿托伐他汀，或安慰剂。

主要观察指标

与安慰剂相比，阿托伐他汀三个剂量水平的总甘油三酯较基线的变化百分比。

结果

治疗4周后，5 mg、20 mg和80 mg阿托伐他汀组与安慰剂组相比，总甘油三酯的平均降低幅度分别为-26.5%、-32.4%、-45.8%和-8.9%。LDL-C的平均降低幅度分别为-16.7%、-33.2%、-41.4%和-1.4%，极低密度脂蛋白胆固醇（VLDL-C）的平均降低幅度分别为-34.3%、-45.9%、-57.7%和-5.5%。观察到总载脂蛋白B（apo B）（-16.9%、-32.8%、-41.7%和+1.0%）、LDL中的apo B（-14.8%、-29.8%、-42.0%和-3.1%）以及VLDL中的apo B（-23.8%、-35.8%、-34.4%和+11.7%）有类似的平均变化。此外，LDL甘油三酯（-22.5%、-30.7%、-39.9%和+3.9%）和VLDL甘油三酯（-28.1%、-34.0%、-47.3%和-10.8%）也有相当的平均变化。