Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia
- Conditions
- Dyslipidemia
- Interventions
- Registration Number
- NCT02304926
- Lead Sponsor
- Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- 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.
- Triglyceride concentration > 400 mg/dl
- Diabetes Mellitus
- Kidney, liver, or thyroid disease
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Simvastatin Simvastatin + Ezetimibe 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. Ezetimibe Simvastatin + 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. Simvastatin 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. Ezetimibe 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.
- Primary Outcome Measures
Name Time Method Triglycerides Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks Triglyceride concentration were measured by enzymatic assay
Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration 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 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 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 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 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 Baseline, 4 weeks and 8 weeks Levels of apolipoprotein B were determined by inmunonephelometry
- Secondary Outcome Measures
Name Time Method Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks 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.
Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system
Membrane Potential Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques
Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques
Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks 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.
Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system
Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay
Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system
Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode
Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques
Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks 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.
Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system
Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration Baseline, 4 weeks and 8 weeks E-selectin was evaluated in serum by Luminex® 200™ system