Clinical trial NCT02304926: Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Dyslipidemia
Keywords: Dyslipidemia
Simvastatin
Ezetimibe
Lipid profile
Inflammation
Oxidative stress
Endothelial function
Lead sponsor: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Sponsor class: OTHER
First posted: 2014-12-02
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Total Cholesterol Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Triglycerides Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
Secondary outcomes:
measure: Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Membrane Potential Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
measure: Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration
timeFrame: Baseline, 4 weeks and 8 weeks
Other outcomes:
Locations:
Study officials:
affiliation: FISABIO - University Hospital Dr Peset
name: Antonio Hernández, MD, Phd
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berneis K, Rizzo M, Berthold HK, Spinas GA, Krone W, Gouni-Berthold I. Ezetimibe alone or in combination with simvastatin increases small dense low-density lipoproteins in healthy men: a randomized trial. Eur Heart J. 2010 Jul;31(13):1633-9. doi: 10.1093/eurheartj/ehq181. Epub 2010 Jun 6.
citation: Florentin M, Liberopoulos EN, Moutzouri E, Rizos CV, Tselepis AD, Elisaf MS. The effect of simvastatin alone versus simvastatin plus ezetimibe on the concentration of small dense low-density lipoprotein cholesterol in subjects with primary hypercholesterolemia. Curr Med Res Opin. 2011 Mar;27(3):685-92. doi: 10.1185/03007995.2010.546394. Epub 2011 Jan 27.
citation: Bays HE, Ose L, Fraser N, Tribble DL, Quinto K, Reyes R, Johnson-Levonas AO, Sapre A, Donahue SR; Ezetimibe Study Group. A multicenter, randomized, double-blind, placebo-controlled, factorial design study to evaluate the lipid-altering efficacy and safety profile of the ezetimibe/simvastatin tablet compared with ezetimibe and simvastatin monotherapy in patients with primary hypercholesterolemia. Clin Ther. 2004 Nov;26(11):1758-73. doi: 10.1016/j.clinthera.2004.11.016.