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Completed

NCT Number: NCT02304926

Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia

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.

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Key information

Conditions

Dyslipidemia Dyslipidemias Inflammation Lipid Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

  • Triglyceride concentration > 400 mg/dl
  • Diabetes Mellitus
  • Kidney, liver, or thyroid disease

Treatment and study plan

simvastatin

Drug

simvastatin (40 mg/day) for 4 weeks

ezetimibe

Drug

ezetimibe (10 mg/day) for 4 weeks

Simvastatin + Ezetimibe

Drug

combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period

Primary outcomes

  1. Total Cholesterol Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Total cholesterol concentration was measured by enzymatic assay

  2. Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the method of Friedewald.

  3. High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    High-density lipoprotein cholesterol (HDLc) concentration was measured using a direct method

  4. Triglycerides Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Triglyceride concentration were measured by enzymatic assay

  5. Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Non-HDLc concentration was obtained by calculating the difference between total cholesterol and HDLc

  6. Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration

    Time frame: 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.

  7. Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Levels of apolipoprotein B were determined by inmunonephelometry

Secondary outcomes

  1. Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay

  2. Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system

  3. Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system

  4. Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode

  5. Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques

  6. Membrane Potential Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques

  7. Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques

  8. Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration

    Time frame: 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.

  9. Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration

    Time frame: 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.

  10. Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration

    Time frame: 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.

  11. Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system

  12. Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system

  13. Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration

    Time frame: Baseline, 4 weeks and 8 weeks

    E-selectin was evaluated in serum by Luminex® 200™ system

Sponsors and collaborators

Lead sponsor

Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

Other

Registry information

Official study title

Study of Lipoprotein Subfractions, Inflammation, Oxidative Stress and Endothelial Function After Treatment With Simvastatin and Ezetimibe Administered Alone and in Combination in Hyperlipidemic Patients

Important dates

Study start
2009
Primary completion
2011
Study completion
2011
First posted
Dec 2, 2014
Registry last updated
Mar 8, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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