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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
42
simvastatin (40 mg/day) for 4 weeks
ezetimibe (10 mg/day) for 4 weeks
combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Total Cholesterol Before and After Simvastatin/Ezetimibe Administration
Total cholesterol concentration was measured by enzymatic assay
Time frame: Baseline, 4 weeks and 8 weeks
Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration
Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the method of Friedewald.
Time frame: Baseline, 4 weeks and 8 weeks
High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration
High-density lipoprotein cholesterol (HDLc) concentration was measured using a direct method
Time frame: Baseline, 4 weeks and 8 weeks
Triglycerides Before and After Simvastatin/Ezetimibe Administration
Triglyceride concentration were measured by enzymatic assay
Time frame: Baseline, 4 weeks and 8 weeks
Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration
Non-HDLc concentration was obtained by calculating the difference between total cholesterol and HDLc
Time frame: Baseline, 4 weeks and 8 weeks
Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration
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.
Time frame: Baseline, 4 weeks and 8 weeks
Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration
Levels of apolipoprotein B were determined by inmunonephelometry
Time frame: Baseline, 4 weeks and 8 weeks
Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration
Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay
Time frame: Baseline, 4 weeks and 8 weeks
Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration
Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system
Time frame: Baseline, 4 weeks and 8 weeks
Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration
Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system
Time frame: Baseline, 4 weeks and 8 weeks
Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration
Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode
Time frame: Baseline, 4 weeks and 8 weeks
Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration
Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques
Time frame: Baseline, 4 weeks and 8 weeks
Membrane Potential Before and After Simvastatin/Ezetimibe Administration
Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques
Time frame: Baseline, 4 weeks and 8 weeks
Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration
Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques
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Time frame: Baseline, 4 weeks and 8 weeks
Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy. Leukocyte rolling was estimated as the number of leukocytes rolling over 100 μm2 of the endothelial monolayer during a 1-min period.
Time frame: Baseline, 4 weeks and 8 weeks
Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy. Adhesion was evaluated by counting the number of polymorphonuclear cells that maintained stable contact with human umbilical vein endothelial cells (HUVEC) for 30 seconds.
Time frame: Baseline, 4 weeks and 8 weeks
Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy.The rolling velocity in the field of focus was determined by measuring the time required by 20 consecutive leukocytes to cover a distance of 100 μm.
Time frame: Baseline, 4 weeks and 8 weeks
Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration
The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system
Time frame: Baseline, 4 weeks and 8 weeks
Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration
The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system
Time frame: Baseline, 4 weeks and 8 weeks
Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration
E-selectin was evaluated in serum by Luminex® 200™ system
Time frame: Baseline, 4 weeks and 8 weeks