在伴有 2 型糖尿病的混合型血脂异常患者中，联合应用低剂量或中等剂量他汀类药物与非诺贝特酸的疗效和安全性：来自三项随机、对照、双盲试验的汇总亚组分析结果。

Efficacy and safety of fenofibric acid co-administered with low- or moderate-dose statin in patients with mixed dyslipidemia and type 2 diabetes mellitus: results of a pooled subgroup analysis from three randomized, controlled, double-blind trials.

机构信息

Baylor College of Medicine, Houston, Texas, USA.

出版信息

Am J Cardiovasc Drugs. 2010;10(2):73-84. doi: 10.2165/10061630-000000000-00000.

DOI:10.2165/10061630-000000000-00000

PMID:20136164

Abstract

BACKGROUND

Monotherapy with lipid-modifying medication is frequently insufficient to normalize lipid abnormalities in patients with mixed dyslipidemia and type 2 diabetes mellitus.

OBJECTIVE

To evaluate the efficacy and safety of fenofibric acid + statin combination therapy in this population.

STUDY DESIGN

A pooled, subgroup analysis of three randomized, controlled, double-blind, 12-week trials.

SETTING

Multiple clinical research facilities in the US and Canada.

PATIENTS

Patients with mixed dyslipidemia and type 2 diabetes (n = 586).

INTERVENTION

Fenofibric acid (Trilipix) 135 mg monotherapy; low-, moderate-, or high-dose statin monotherapy (rosuvastatin [Crestor] 10, 20, or 40 mg; simvastatin [Zocor] 20, 40, or 80 mg; or atorvastatin [Lipitor] 20, 40, or 80 mg); or fenofibric acid + low- or moderate-dose statin.

MAIN OUTCOME MEASURE

Mean percentage changes in lipid parameters, percentages of patients achieving optimal serum lipid/apolipoprotein levels, and incidence of adverse events.

RESULTS

Fenofibric acid + low-dose statin resulted in significantly (p < 0.001) greater mean percentage changes in high-density lipoprotein cholesterol (HDL-C) [16.8%] and triglycerides (-43.9%) than low-dose statin monotherapy (4.7% and -18.1%, respectively) and significantly (p < 0.001) greater reductions in low-density lipoprotein cholesterol (LDL-C) [-34.0%] than fenofibric acid monotherapy (-5.3%). Similarly, fenofibric acid + moderate-dose statin resulted in significantly (p < or = 0.011) greater mean percentage changes in HDL-C (16.3%) and triglycerides (-43.4%) than moderate-dose statin monotherapy (8.7% and -24.2%, respectively) and significantly (p < 0.001) greater reductions in LDL-C (-32.6%) than fenofibric acid monotherapy (-5.3%). Compared with low- or moderate-dose statin, fenofibric acid + low- or moderate-dose statin resulted in over 5-fold higher percentages of patients achieving optimal levels of LDL-C, non-HDL-C, apolipoprotein B, HDL-C, and triglycerides simultaneously. Incidence of adverse events was generally similar among treatments.

CONCLUSION

Fenofibric acid + statin combination therapy in patients with mixed dyslipidemia and type 2 diabetes was well tolerated and resulted in more comprehensive improvement in the lipid/apolipoprotein profile than either monotherapy. [Clinical trials are registered at www.clinicaltrials.gov: NCT00300482, NCT00300456, and NCT00300469].

摘要

背景

对于同时患有混合性血脂异常和 2 型糖尿病的患者，单独使用调脂药物通常不足以使血脂异常正常化。

目的

评估在该人群中使用非诺贝特酸联合他汀类药物的疗效和安全性。

研究设计

三项随机、对照、双盲、12 周试验的汇总、亚组分析。

地点

美国和加拿大的多个临床研究机构。

患者

患有混合性血脂异常和 2 型糖尿病的患者（n = 586）。

干预措施

非诺贝特酸（力平脂）135 mg 单药治疗；低、中、高剂量他汀类药物单药治疗（瑞舒伐他汀[可定]10、20 或 40 mg；辛伐他汀[舒降之]20、40 或 80 mg；或阿托伐他汀[立普妥]20、40 或 80 mg）；或非诺贝特酸+低或中剂量他汀类药物。

主要观察指标

血脂参数的平均百分比变化、达到最佳血清血脂/载脂蛋白水平的患者百分比以及不良事件的发生率。

结果

非诺贝特酸+低剂量他汀类药物治疗与低剂量他汀类药物单药治疗相比（分别为 4.7%和-18.1%），显著（p < 0.001）增加了高密度脂蛋白胆固醇（HDL-C）（16.8%）和甘油三酯（-43.9%）的平均百分比变化，与非诺贝特酸单药治疗相比（分别为-5.3%），显著（p < 0.001）降低了低密度脂蛋白胆固醇（LDL-C）（-34.0%）。同样，非诺贝特酸+中剂量他汀类药物治疗与中剂量他汀类药物单药治疗相比（分别为 8.7%和-24.2%），显著（p < 0.011）增加了 HDL-C（16.3%）和甘油三酯（-43.4%）的平均百分比变化，与非诺贝特酸单药治疗相比（分别为-5.3%），显著（p < 0.001）降低了 LDL-C（-32.6%）。与低或中剂量他汀类药物相比，非诺贝特酸+低或中剂量他汀类药物治疗使同时达到 LDL-C、非 HDL-C、载脂蛋白 B、HDL-C 和甘油三酯最佳水平的患者比例提高了 5 倍以上。不良事件的发生率在各治疗组之间通常相似。