瑞舒伐他汀可降低伴有脂蛋白脂酶缺乏症（弗雷德里克森 III 型高脂蛋白血症）的患者的非高密度脂蛋白胆固醇和脂蛋白残粒。

Rosuvastatin reduces non-high-density lipoprotein cholesterol and lipoprotein remnants in patients with dysbetalipoproteinemia (Fredrickson type III hyperlipoproteinemia).

机构信息

Lipidology Division of Internal Medicine, Groote Schuur Hospital and University of Cape Town, Lipid Laboratory, 5th Floor, Christiaan Barnard Building, UCT Faculty of Health Sciences, Anzio Road, 7925 Observatory Cape Town, South Africa.

出版信息

J Clin Lipidol. 2008 Dec;2(6):418-25. doi: 10.1016/j.jacl.2008.10.002. Epub 2008 Nov 1.

DOI:10.1016/j.jacl.2008.10.002

PMID:21291775

Abstract

BACKGROUND

Dysbetalipoproteinemia is an uncommon genetic disorder characterized by accumulation of plasma remnant lipoproteins, severe mixed dyslipidemia, elevated apolipoprotein E levels, accelerated atherosclerosis, and premature cardiovascular disease.

OBJECTIVE

To evaluate the efficacy and safety of rosuvastatin in patients with dysbetalipoproteinemia.

METHODS

Following a 6-week washout, 32 patients with dysbetalipoproteinemia received rosuvastatin 10 mg, rosuvastatin 20 mg, and pravastatin 40 mg, each for 6 weeks in a randomized, double-blind, three-way crossover design. Patients subsequently entered an 18-week open-label phase in which the rosuvastatin dosage could be increased from 20 mg to a maximum of 40 mg at 6 weekly intervals to reach National Cholesterol Education Program goals for non-high-density lipoprotein cholesterol (non-HDL-C) and optimal triglyceride (TG). Fibrates (except gemfibrozil) could be added if patients were not at goal on rosuvastatin 40 mg. The primary efficacy variable was percent change from baseline in non-HDL-C during the double-blind phase. The prespecified efficacy criterion was for the 95% confidence interval (CI) of non-HDL-C to lie entirely below -25% for any rosuvastatin dose.

RESULTS

Following drug washout, median total cholesterol was 8.86 mmol/L, non-HDL-C 7.61 mmol/L, and TG 5.69 mmol/L. After 6-week treatment, median change in non-HDL-C was -48.2% (95% CI -56.7% to -45.6%) for rosuvastatin 10 mg, -56.4% (95% CI -61.4% to -48.5%) for rosuvastatin 20 mg, and -35.1% (95% CI -41.6% to -29.6%) for pravastatin 40 mg. Rosuvastatin increased HDL-C and apolipoprotein A-I and substantially reduced total, very low-, intermediate-, and low-density lipoprotein cholesterol and TG, and corresponding apolipoproteins. Efficacy was maintained in the open-label phase, with reduction in non-HDL-C of -61.5%, -62.8% and -65.8% at weeks 24, 30 and 36, respectively. All treatments were well tolerated.

CONCLUSION

Rosuvastatin 10 and 20 mg favorably modify the dyslipidemia of patients with dysbetalipoproteinemia.

摘要

背景

β-脂蛋白血症是一种罕见的遗传性疾病，其特征为血浆残粒脂蛋白堆积、严重混合性血脂异常、载脂蛋白 E 水平升高、动脉粥样硬化加速以及心血管疾病的过早发生。

目的

评估瑞舒伐他汀治疗β-脂蛋白血症患者的疗效和安全性。

方法

在为期 6 周的洗脱期后，32 例β-脂蛋白血症患者接受瑞舒伐他汀 10mg、瑞舒伐他汀 20mg 和普伐他汀 40mg 治疗，采用随机、双盲、三交叉设计，每 6 周为一个周期，共治疗 6 周。随后患者进入为期 18 周的开放标签阶段，瑞舒伐他汀的剂量可在 6 周的间隔内从 20mg 增加至最大 40mg，以达到非高密度脂蛋白胆固醇（非-HDL-C）和最佳甘油三酯（TG）的国家胆固醇教育计划目标。如果患者服用瑞舒伐他汀 40mg 仍未达到目标，可加用贝特类药物（除外吉非贝齐）。主要疗效变量是非-HDL-C 在双盲阶段的基线百分比变化。预先指定的疗效标准是瑞舒伐他汀任何剂量的非-HDL-C 95%置信区间（CI）完全低于-25%。

结果

药物洗脱后，总胆固醇中位数为 8.86mmol/L，非-HDL-C 中位数为 7.61mmol/L，TG 中位数为 5.69mmol/L。经过 6 周的治疗，瑞舒伐他汀 10mg、瑞舒伐他汀 20mg 和普伐他汀 40mg 组非-HDL-C 的中位变化分别为-48.2%（95%CI-56.7%至-45.6%）、-56.4%（95%CI-61.4%至-48.5%）和-35.1%（95%CI-41.6%至-29.6%）。瑞舒伐他汀增加了高密度脂蛋白胆固醇和载脂蛋白 A-I，显著降低了总胆固醇、极低密度脂蛋白胆固醇、中间密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯以及相应的载脂蛋白。在开放标签阶段疗效得到维持，第 24、30 和 36 周时非-HDL-C 的降低分别为-61.5%、-62.8%和-65.8%。所有治疗均耐受良好。