Trial Outcomes & Findings for Effects of Simvastatin and Ezetimibe on Cardiovascular Risk Markers in Patients With Dyslipidemia (NCT NCT02304926)

NCT ID: NCT02304926

Last Updated: 2018-03-08

Results Overview

Total cholesterol concentration was measured by enzymatic assay

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 42 participants
• Primary outcome timeframe: Baseline, 4 weeks and 8 weeks
• Results posted on: 2018-03-08

Participant Flow

Participant milestones

Measure	Simvastatin 20 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe 20 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Overall Study STARTED	22	20
Overall Study COMPLETED	20	19
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	Simvastatin 20 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe 20 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Overall Study Lost to Follow-up	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Simvastatin n=20 Participants 20 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 20 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Total n=39 Participants Total of all reporting groups
Age, Continuous	57.7 years STANDARD_DEVIATION 12.7 • n=93 Participants	57.6 years STANDARD_DEVIATION 10.2 • n=4 Participants	57.7 years STANDARD_DEVIATION 11.5 • n=27 Participants
Sex: Female, Male Female	15 Participants n=93 Participants	16 Participants n=4 Participants	31 Participants n=27 Participants
Sex: Female, Male Male	5 Participants n=93 Participants	3 Participants n=4 Participants	8 Participants n=27 Participants
Body mass index	28.6 Kg/m2 STANDARD_DEVIATION 3.9 • n=93 Participants	31.2 Kg/m2 STANDARD_DEVIATION 7.3 • n=4 Participants	29.8 Kg/m2 STANDARD_DEVIATION 5.6 • n=27 Participants
Systolic blood pressure	133 mm Hg STANDARD_DEVIATION 17 • n=93 Participants	137 mm Hg STANDARD_DEVIATION 14 • n=4 Participants	134 mm Hg STANDARD_DEVIATION 15 • n=27 Participants
Diastolic blood pressure (mm Hg)	79 mm Hg STANDARD_DEVIATION 10 • n=93 Participants	80 mm Hg STANDARD_DEVIATION 7 • n=4 Participants	80 mm Hg STANDARD_DEVIATION 8 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

Total cholesterol concentration was measured by enzymatic assay

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Total Cholesterol Before and After Simvastatin/Ezetimibe Administration Baseline	255 mg/dl Standard Deviation 34	253 mg/dl Standard Deviation 26
Total Cholesterol Before and After Simvastatin/Ezetimibe Administration 4 weeks	180 mg/dl Standard Deviation 29	215 mg/dl Standard Deviation 33
Total Cholesterol Before and After Simvastatin/Ezetimibe Administration 8 weeks	173 mg/dl Standard Deviation 38	169 mg/dl Standard Deviation 39

PRIMARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration Baseline	178 mg/dl Standard Deviation 26	172 mg/dl Standard Deviation 29
Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration 4 weeks	106 mg/dl Standard Deviation 18	138 mg/dl Standard Deviation 32
Low-density Lipoprotein Cholesterol (LDLc) Before and After Simvastatin/Ezetimibe Administration 8 weeks	98 mg/dl Standard Deviation 28	94 mg/dl Standard Deviation 36

PRIMARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration Baseline	47 mg/dl Standard Deviation 11	53 mg/dl Standard Deviation 15
High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration 4 weeks	50 mg/dl Standard Deviation 13	53 mg/dl Standard Deviation 11
High-density Lipoprotein Cholesterol (HDLc) Before and After Simvastatin/Ezetimibe Administration 8 weeks	51 mg/dl Standard Deviation 13	53 mg/dl Standard Deviation 13

PRIMARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

Triglyceride concentration were measured by enzymatic assay

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Triglycerides Before and After Simvastatin/Ezetimibe Administration Baseline	141 mg/dl Interval 104.0 to 168.0	120 mg/dl Interval 81.0 to 184.0
Triglycerides Before and After Simvastatin/Ezetimibe Administration 4 weeks	117 mg/dl Interval 82.0 to 136.0	105 mg/dl Interval 81.0 to 142.0
Triglycerides Before and After Simvastatin/Ezetimibe Administration 8 weeks	104 mg/dl Interval 82.0 to 146.0	81 mg/dl Interval 61.0 to 137.0

PRIMARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration 4 weeks	130 mg/dl Standard Deviation 23	162 mg/dl Standard Deviation 33
Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration 8 weeks	122 mg/dl Standard Deviation 31	115 mg/dl Standard Deviation 39
Non-HDL Cholesterol Before and After Simvastatin/Ezetimibe Administration Baseline	208 mg/dl Standard Deviation 29	200 mg/dl Standard Deviation 28

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration Baseline	268.1 Angström Standard Deviation 4.7	270.4 Angström Standard Deviation 2.3
Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration 4 weeks	270.4 Angström Standard Deviation 2.9	271.5 Angström Standard Deviation 2.2
Low Density Lipoprotein Size Before and After Simvastatin/Ezetimibe Administration 8 weeks	271.7 Angström Standard Deviation 2.7	272.0 Angström Standard Deviation 1.9

PRIMARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

Levels of apolipoprotein B were determined by inmunonephelometry

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration Baseline	139 mg/dl Standard Deviation 20	127 mg/dl Standard Deviation 23
Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration 4 weeks	92 mg/dl Standard Deviation 18	110 mg/dl Standard Deviation 24
Apolipoprotein B Before and After Simvastatin/Ezetimibe Administration 8 weeks	84 mg/dl Standard Deviation 18	79 mg/dl Standard Deviation 29

SECONDARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration Baseline	4.02 mg/l Standard Deviation 3.49	4.43 mg/l Standard Deviation 4.97
Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration 4 weeks	2.82 mg/l Standard Deviation 2.69	3.98 mg/l Standard Deviation 3.65
Levels of High-sensitive C-reactive Protein (hsCRP) Before and After Simvastatin/Ezetimibe Administration 8 weeks	2.64 mg/l Standard Deviation 2.21	3.31 mg/l Standard Deviation 3.48

SECONDARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration Baseline	2.44 pg/ml Standard Deviation 1.62	2.94 pg/ml Standard Deviation 1.45
Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration 4 weeks	2.83 pg/ml Standard Deviation 1.66	3.93 pg/ml Standard Deviation 2.28
Levels of Interleukin-6 (IL-6) Before and After Simvastatin/Ezetimibe Administration 8 weeks	4.43 pg/ml Standard Deviation 4.30	5.78 pg/ml Standard Deviation 3.98

SECONDARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration Baseline	3.43 pg/ml Standard Deviation 1.87	3.01 pg/ml Standard Deviation 2.29
Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration 4 weeks	3.99 pg/ml Standard Deviation 1.77	5.09 pg/ml Standard Deviation 5.23
Levels of Tumor Necrosis Factor α (TNF-α) Before and After Simvastatin/Ezetimibe Administration 8 weeks	4.43 pg/ml Standard Deviation 4.30	4.35 pg/ml Standard Deviation 4.09

SECONDARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration Baseline	1.09 Nmol O2/min/million cells Standard Deviation 0.15	1.09 Nmol O2/min/million cells Standard Deviation 0.15
Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration 4 weeks	1.54 Nmol O2/min/million cells Standard Deviation 0.12	1.31 Nmol O2/min/million cells Standard Deviation 0.13
Mitochondrial Oxygen (O2) Consumption Before and After Simvastatin/Ezetimibe Administration 8 weeks	1.76 Nmol O2/min/million cells Standard Deviation 0.21	1.67 Nmol O2/min/million cells Standard Deviation 0.10

SECONDARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration Baseline	74.7 Fluorescence Units Standard Deviation 8.1	72.8 Fluorescence Units Standard Deviation 8.3
Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration 4 weeks	57.2 Fluorescence Units Standard Deviation 8.9	63.5 Fluorescence Units Standard Deviation 10.3
Reactive Oxygen Species (ROS) Production Before and After Simvastatin/Ezetimibe Administration 8 weeks	43.3 Fluorescence Units Standard Deviation 7.9	48.9 Fluorescence Units Standard Deviation 3.3

SECONDARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Membrane Potential Before and After Simvastatin/Ezetimibe Administration Baseline	46.6 Fluorescence Units Standard Deviation 5.8	48.4 Fluorescence Units Standard Deviation 3.9
Membrane Potential Before and After Simvastatin/Ezetimibe Administration 4 weeks	62.5 Fluorescence Units Standard Deviation 5.4	56.7 Fluorescence Units Standard Deviation 5.4
Membrane Potential Before and After Simvastatin/Ezetimibe Administration 8 weeks	70.4 Fluorescence Units Standard Deviation 8.4	67.5 Fluorescence Units Standard Deviation 4.5

SECONDARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration Baseline	2.68 Fluorescence Units Standard Deviation 0.63	2.85 Fluorescence Units Standard Deviation 0.71
Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration 4 weeks	5.67 Fluorescence Units Standard Deviation 0.59	3.79 Fluorescence Units Standard Deviation 0.67
Levels of Glutathione (GSH) Before and After Simvastatin/Ezetimibe Administration 8 weeks	7.92 Fluorescence Units Standard Deviation 1.24	7.51 Fluorescence Units Standard Deviation 1.09

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration Baseline	412 polymorphonuclear cells/min Standard Deviation 132	421 polymorphonuclear cells/min Standard Deviation 203
Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration 4 weeks	225 polymorphonuclear cells/min Standard Deviation 61	392 polymorphonuclear cells/min Standard Deviation 187
Leukocyte Rolling Flux Before and After Simvastatin/Ezetimibe Administration 8 weeks	147 polymorphonuclear cells/min Standard Deviation 51	196 polymorphonuclear cells/min Standard Deviation 99

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration Baseline	25.1 polymorphonuclear cells/mm2 Standard Deviation 8.2	25.6 polymorphonuclear cells/mm2 Standard Deviation 12.1
Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration 4 weeks	15.0 polymorphonuclear cells/mm2 Standard Deviation 4.1	23.8 polymorphonuclear cells/mm2 Standard Deviation 14.2
Leukocyte Adhesion Before and After Simvastatin/Ezetimibe Administration 8 weeks	10.9 polymorphonuclear cells/mm2 Standard Deviation 2.5	12.5 polymorphonuclear cells/mm2 Standard Deviation 4.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration Baseline	469 micrometer/second Standard Deviation 53	524 micrometer/second Standard Deviation 43
Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration 4 weeks	553 micrometer/second Standard Deviation 54	533 micrometer/second Standard Deviation 42
Leukocyte Rolling Velocity Before and After Simvastatin/Ezetimibe Administration 8 weeks	608 micrometer/second Standard Deviation 43	629 micrometer/second Standard Deviation 34

SECONDARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration Baseline	1314 ng/ml Standard Deviation 251	1371 ng/ml Standard Deviation 342
Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration 4 weeks	1137 ng/ml Standard Deviation 407	1166 ng/ml Standard Deviation 526
Levels of Vascular Cell Adhesion Molecule 1 (VCAM-1) Before and After Simvastatin/Ezetimibe Administration 8 weeks	1074 ng/ml Standard Deviation 385	1220 ng/ml Standard Deviation 201

SECONDARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration Baseline	188 ng/ml Standard Deviation 46.5	160.6 ng/ml Standard Deviation 37.8
Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration 4 weeks	139.5 ng/ml Standard Deviation 53.4	114.7 ng/ml Standard Deviation 24.6
Levels of Intercellular Adhesion Molecule 1 (ICAM-1) Before and After Simvastatin/Ezetimibe Administration 8 weeks	122.2 ng/ml Standard Deviation 52.2	108.1 ng/ml Standard Deviation 36.1

SECONDARY outcome

Timeframe: Baseline, 4 weeks and 8 weeks

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

Outcome measures

Measure	Simvastatin n=20 Participants 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: simvastatin (40 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period	Ezetimibe n=19 Participants 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. Ezetimibe: ezetimibe (10 mg/day) for 4 weeks Simvastatin + Ezetimibe: combined therapy simvastatin (40 mg/day) + ezetimibe (10 mg/day) for 4-week period
Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration Baseline	45.1 ng/ml Standard Deviation 21.0	39.7 ng/ml Standard Deviation 15.6
Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration 4 weeks	38.9 ng/ml Standard Deviation 16.0	30.5 ng/ml Standard Deviation 14.7
Levels of E-selectin Before and After Simvastatin/Ezetimibe Administration 8 weeks	29.2 ng/ml Standard Deviation 11.0	24.4 ng/ml Standard Deviation 9.1

Adverse Events

Adverse Events Were Not Collected

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr Antonio Hernández

FISABIO-University Hospital Dr Peset

Phone: 961622492

Email: hernandez_antmij@gva.es

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place