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

NCT02304926 | Completed Results

• 1 other identifier: SIM-EZE-2009-01
• Study Type: interventional
• Target: 42
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Dyslipidemia

Keywords

Dyslipidemia; Simvastatin; Ezetimibe; Lipid profile; Inflammation; Oxidative stress; Endothelial function

Outcome Measures

Primary Outcomes (7)

• Total Cholesterol Before and After Simvastatin/Ezetimibe Administration

  Total cholesterol concentration was measured by enzymatic assay

  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.

  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

  Baseline, 4 weeks and 8 weeks

• Triglycerides Before and After Simvastatin/Ezetimibe Administration

  Triglyceride concentration were measured by enzymatic assay

  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

  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.

  Baseline, 4 weeks and 8 weeks

• Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration

  Levels of apolipoprotein B were determined by inmunonephelometry

  Baseline, 4 weeks and 8 weeks

Secondary Outcomes (13)

• 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

• Levels of Tumor Necrosis Factor α (TNF-α) 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

Study Arms (2)

Simvastatin

EXPERIMENTAL

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.

Drug: Simvastatin; Drug: Simvastatin + Ezetimibe

Ezetimibe

EXPERIMENTAL

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.

Drug: Ezetimibe; Drug: Simvastatin + Ezetimibe

Interventions

Simvastatin DRUG

simvastatin (40 mg/day) for 4 weeks

Simvastatin

Ezetimibe DRUG

ezetimibe (10 mg/day) for 4 weeks

Ezetimibe

Simvastatin + Ezetimibe DRUG

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

Ezetimibe; Simvastatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

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

Related Publications (3)

• 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.

  PMID: 20525999 BACKGROUND

• 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.

  PMID: 21271793 BACKGROUND

• 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.

  PMID: 15639688 BACKGROUND

MeSH Terms

Conditions

Dyslipidemias; Inflammation

Interventions

Simvastatin; Ezetimibe; Ezetimibe, Simvastatin Drug Combination

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr Antonio Hernández
• Organization: FISABIO-University Hospital Dr Peset

hernandez_antmij@gva.es

961622492

Study Officials

• Antonio Hernández, MD, Phd

  FISABIO - University Hospital Dr Peset

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Phd

Study Record Dates

• First Submitted: November 25, 2014
• First Posted: December 2, 2014
• Study Start: January 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: March 8, 2018
• Results First Posted: May 21, 2015

Record last verified: 2018-02