Study of Lipoprotein Subfractions, Inflammation, Oxidative Stress and Endothelial Function After Treatment With Simvastatin and Ezetimibe Administered Alone and in Combination in Hyperlipidemic Patients
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 主要终点
- Triglycerides Before and After Simvastatin/Ezetimibe Administration
研究概览
简要总结
Coadministration of drugs is common in the pharmacologic treatment of dyslipidemia, with statins and ezetimibe generally constituting the medication of choice. By acting at different levels, the combination of these drugs allows the therapeutic objective to be achieved. However, it is not known how these drugs qualitatively affect the composition of lipoprotein subfractions, which differ in size and atherogenic potential. The investigators set out to evaluate this effect as well as their effects on inflammatory, oxidative stress and endothelial function parameters.
详细描述
The study consisted of a randomised parallel trial and took place during a period of 2 months. A total of 42 hyperlipidemic patients were randomly assigned to one of 2 groups: one received simvastatin (40 mg/day) and the other received ezetimibe (10 mg/day) for 4 weeks, after which both groups were administered combined therapy for an additional 4-week period. Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •LDL cholesterol concentration of between 160-190 mg/dl in patients with less than 2 cardiovascular risk factors
- •LDL concentration of between 130-160 mg/dl in patients that presented 2 or more cardiovascular risk factors.
- •Cardiovascular risk factors were defined as: age (≥ 45 years in men and ≥55 years in women), a smoking habit, hypertension (≥140/90 mmHg), diabetes mellitus, a high-density lipoprotein (HDL) cholesterol concentration of ≤ 40mg/dl, and a family history of cardiovascular disease.
排除标准
- •Triglyceride concentration > 400 mg/dl
- •Diabetes Mellitus
- •Kidney, liver, or thyroid disease
研究组 & 干预措施
Simvastatin
Hyperlipidemic patients received simvastatin (40 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period. Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
干预措施: Simvastatin (Drug)
Simvastatin
Hyperlipidemic patients received simvastatin (40 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period. Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
干预措施: Simvastatin + Ezetimibe (Drug)
Ezetimibe
Hyperlipidemic patients received ezetimibe (10 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period. Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
干预措施: Ezetimibe (Drug)
Ezetimibe
Hyperlipidemic patients received ezetimibe (10 mg/day) for 4 weeks, after they were administered combined therapy (simvastatin, 40 mg/day plus ezetimibe,10 mg/day) for an additional 4-week period. Lipid profile, lipoprotein subfractions of LDL and HDL, inflammatory, oxidative stress and endothelial function parameters were evaluated.
干预措施: Simvastatin + Ezetimibe (Drug)
结局指标
主要结局
Triglycerides Before and After Simvastatin/Ezetimibe Administration
时间窗: Baseline, 4 weeks and 8 weeks
Triglyceride concentration were measured by enzymatic assay
Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration
时间窗: Baseline, 4 weeks and 8 weeks
Non-HDLc concentration was obtained by calculating the difference between total cholesterol and HDLc
Total Cholesterol Before and After Simvastatin/Ezetimibe Administration
时间窗: Baseline, 4 weeks and 8 weeks
Total cholesterol concentration was measured by enzymatic assay
Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration
时间窗: Baseline, 4 weeks and 8 weeks
Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the method of Friedewald.
High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration
时间窗: Baseline, 4 weeks and 8 weeks
High-density lipoprotein cholesterol (HDLc) concentration was measured using a direct method
Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration
时间窗: Baseline, 4 weeks and 8 weeks
LDL subfractions were separated by high-resolution polyacrylamide gel tubes using the Lipoprint® system. The LDL electrophoretic profile allows 2 patterns to be defined: pattern A or large and buoyant LDL, and pattern non-A or small and dense LDL.
Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration
时间窗: Baseline, 4 weeks and 8 weeks
Levels of apolipoprotein B were determined by inmunonephelometry
次要结局
- Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Membrane Potential Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
- Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration(Baseline, 4 weeks and 8 weeks)
研究者
Antonio Hernandez Mijares
MD, Phd
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana