Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia
6 februari 2018 uppdaterad av: Antonio Hernandez Mijares, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Study of Lipoprotein Subfractions, Inflammation, Oxidative Stress and Endothelial Function After Treatment With Simvastatin and Ezetimibe Administered Alone and in Combination in Hyperlipidemic Patients
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.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
42
Fas
- Inte tillämpbar
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år och äldre (Vuxen, Äldre vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Experimentell: 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.
|
simvastatin (40 mg/day) for 4 weeks
combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
|
|
Experimentell: 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.
|
combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
ezetimibe (10 mg/day) for 4 weeks
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Total Cholesterol Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
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
Tidsram: Baseline, 4 weeks and 8 weeks
|
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
Tidsram: Baseline, 4 weeks and 8 weeks
|
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
Tidsram: Baseline, 4 weeks and 8 weeks
|
Triglyceride concentration were measured by enzymatic assay
|
Baseline, 4 weeks and 8 weeks
|
|
Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
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
Tidsram: 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.
|
Baseline, 4 weeks and 8 weeks
|
|
Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
Levels of apolipoprotein B were determined by inmunonephelometry
|
Baseline, 4 weeks and 8 weeks
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
|---|---|---|
|
Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
Levels of high-sensitive C-reactive protein (hsCRP) were analysed by a latex-enhanced inmunonephelometric assay
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
Levels of proinflammatory cytokines (interleukin-6 (IL-6)) were analysed with a Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
Levels of proinflammatory cytokines (tumor necrosis factor α (TNF-α)) were analysed with a Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (mitochondrial oxygen (O2) consumption) was measured at baseline and after treatment by Clark electrode
|
Baseline, 4 weeks and 8 weeks
|
|
Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (Reactive oxygen species (ROS) production) was measured at baseline and after treatment by fluorometric techniques
|
Baseline, 4 weeks and 8 weeks
|
|
Membrane Potential Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (membrane potential) was measured at baseline and after treatment by fluorometric techniques
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
Oxidative stress markers (levels of glutathione (GSH)) was measured at baseline and after treatment by fluorometric techniques
|
Baseline, 4 weeks and 8 weeks
|
|
Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration
Tidsram: 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.
|
Baseline, 4 weeks and 8 weeks
|
|
Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration
Tidsram: 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.
|
Baseline, 4 weeks and 8 weeks
|
|
Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration
Tidsram: 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.
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
The vascular cell adhesion molecule 1 (VCAM-1) was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
The intercellular adhesion molecule 1 (ICAM-1) was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
|
Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration
Tidsram: Baseline, 4 weeks and 8 weeks
|
E-selectin was evaluated in serum by Luminex® 200™ system
|
Baseline, 4 weeks and 8 weeks
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Utredare
- Huvudutredare: Antonio Hernández, MD, Phd, FISABIO - University Hospital Dr Peset
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- 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.
- 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.
- 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.
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 januari 2009
Primärt slutförande (Faktisk)
1 december 2011
Avslutad studie (Faktisk)
1 december 2011
Studieregistreringsdatum
Först inskickad
25 november 2014
Först inskickad som uppfyllde QC-kriterierna
26 november 2014
Första postat (Uppskatta)
2 december 2014
Uppdateringar av studier
Senaste uppdatering publicerad (Faktisk)
8 mars 2018
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
6 februari 2018
Senast verifierad
1 februari 2018
Mer information
Termer relaterade till denna studie
Ytterligare relevanta MeSH-villkor
- Metaboliska sjukdomar
- Lipidmetabolismstörningar
- Dyslipidemier
- Molekylära mekanismer för farmakologisk verkan
- Enzyminhibitorer
- Antimetaboliter
- Antikolesteremiska medel
- Hypolipidemiska medel
- Lipidreglerande medel
- Hydroximetylglutaryl-CoA-reduktashämmare
- Simvastatin
- Ezetimib
- Ezetimib, Simvastatin Läkemedelskombination
Andra studie-ID-nummer
- SIM-EZE-2009-01
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .