Ezetimibe/Simvastatin in Patients With Metabolic Syndrome (0653A-107)(COMPLETED)

• Sponsor: Organon and Co (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00409773
• Collaborator: (none)
• Enrollment: 1,143
• Arms: 5
• Duration (Months): 18

Study Details

Study Description

Brief Summary

A 6-week clinical trial in patients with metabolic syndrome and hypercholesterolemia at high risk for coronary heart disease to study the effects of ezetimibe/simvastatin and atorvastatin on lipids.

Condition or Disease	Intervention/Treatment	Phase
Hypercholesterolemia; Metabolic Syndrome	Drug: ezetimibe (+) simvastatin; Drug: Comparator: atorvastatin calcium; Drug: Comparator: Placebo (unspecified)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1143 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Randomized, Double-Blind, Parallel Arm, 6-Week Study to Evaluate the Efficacy and Safety of Ezetimibe/Simvastatin Versus Atorvastatin in Patients With Metabolic Syndrome and Hypercholesterolemia at High Risk for Coronary Heart Disease
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Other: 1 Arm 1: drug + comparator + Placebo	Drug: ezetimibe (+) simvastatin; Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg or 10/40 mg.; Other Names: MK0653A Vytorin® ; Drug: Comparator: atorvastatin calcium; Atorvastatin will be supplied in 10mg, 20mg and 40mg tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.; Other Names: Lipitor ® ; Drug: Comparator: Placebo (unspecified); Atorvastatin Placebo will be supplied in 10mg, 20mg and 40mg tablets. ezetimibe/simvastatin Placebo will be supplied in 10/20mg and 10/40mg combination tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.
Other: 2 Arm 2: drug + comparator + Placebo	Drug: ezetimibe (+) simvastatin; Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg or 10/40 mg.; Other Names: MK0653A Vytorin® ; Drug: Comparator: atorvastatin calcium; Atorvastatin will be supplied in 10mg, 20mg and 40mg tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.; Other Names: Lipitor ® ; Drug: Comparator: Placebo (unspecified); Atorvastatin Placebo will be supplied in 10mg, 20mg and 40mg tablets. ezetimibe/simvastatin Placebo will be supplied in 10/20mg and 10/40mg combination tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.
Other: 3 Arm 3: drug + comparator + Placebo	Drug: ezetimibe (+) simvastatin; Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg or 10/40 mg.; Other Names: MK0653A Vytorin® ; Drug: Comparator: atorvastatin calcium; Atorvastatin will be supplied in 10mg, 20mg and 40mg tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.; Other Names: Lipitor ® ; Drug: Comparator: Placebo (unspecified); Atorvastatin Placebo will be supplied in 10mg, 20mg and 40mg tablets. ezetimibe/simvastatin Placebo will be supplied in 10/20mg and 10/40mg combination tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.
Other: 4 Arm 4: drug + comparator + Placebo	Drug: ezetimibe (+) simvastatin; Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg or 10/40 mg.; Other Names: MK0653A Vytorin® ; Drug: Comparator: atorvastatin calcium; Atorvastatin will be supplied in 10mg, 20mg and 40mg tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.; Other Names: Lipitor ® ; Drug: Comparator: Placebo (unspecified); Atorvastatin Placebo will be supplied in 10mg, 20mg and 40mg tablets. ezetimibe/simvastatin Placebo will be supplied in 10/20mg and 10/40mg combination tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.
Other: 5 Arm 5: drug + comparator + Placebo	Drug: ezetimibe (+) simvastatin; Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg or 10/40 mg.; Other Names: MK0653A Vytorin® ; Drug: Comparator: atorvastatin calcium; Atorvastatin will be supplied in 10mg, 20mg and 40mg tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.; Other Names: Lipitor ® ; Drug: Comparator: Placebo (unspecified); Atorvastatin Placebo will be supplied in 10mg, 20mg and 40mg tablets. ezetimibe/simvastatin Placebo will be supplied in 10/20mg and 10/40mg combination tablets. Each patient will receive 1 active treatment dose & 2 Placebo doses at randomization according to a predetermined partial blinding schedule to reduce the number of pills from 5 to 3 per patient per day for 6 weeks.

Outcome Measures

Primary Outcome Measures

1. Percent Change From Baseline in Low Density Lipoprotein (LDL-C) at Week 6 [Baseline and 6 Weeks]

Secondary Outcome Measures

1. Percent Change From Baseline in Total Cholesterol(mg/dL) at Week 6 [Baseline and 6 Weeks]

2. Percent Change From Baseline in Triglyceride (TG) (mg/dL) at Week 6 [Baseline and 6 Weeks]

3. Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 6 [Baseline and 6 Weeks]

4. Percent Change From Baseline in Non- High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 6 [Baseline and 6 Weeks]

5. Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 6 [Baseline and 6 Weeks]

6. Percent Change From Baseline in Apolipoprotein- B (Apo-B) at Week 6 [Baseline and 6 Weeks]

7. Percent Change From Baseline in Apolipoprotein-A1 (Apo-A1) at Week 6 [Baseline and 6 Weeks]

8. Percent Change From Baseline in Total-Cholesterol: High Density Lipoprotein-Cholesterol (Total-C:HDL- C) at Week 6 [Baseline and 6 Weeks]

9. Percent Change From Baseline in Low Density Lipoprotein Cholesterol: High Density Lipoprotein Cholesterol (LDL-C: HDL-C) at Week 6 [Baseline and 6 Weeks]

10. Percent Change From Baseline in Apolipoprotein-B: Apolipoprotein-A1 (Apo-B:Apo-A1) at Week 6 [Baseline and 6 weeks]

11. Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol: High Density Lipoprotein Cholesterol (Non-HDL-C:HDL-C) at Week 6 [Baseline and 6 Weeks]

12. Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 6 in Patients With Atherosclerotic Vascular Disease (AVD) [Baseline and 6 Weeks]

13. Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 6 in Patients Without Atherosclerotic Vascular Disease (AVD) [Baseline and 6 Weeks]

14. Percent Change From Baseline in High-Sensitivity C-reactive (Hs-CRP) (mg/dL) at Week 6 [Baseline and 6 Weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 79 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients 18 to 79 years of age with metabolic syndrome and hypercholesterolemia at high risk for coronary heart disease (CHD) with LDL-C above 70 mg/dL or 100 mg/dL depending on their CHD risk category

Exclusion Criteria:

• A condition which, in the opinion of the investigator, pose a risk to the patient or interfere with participating in the study

• Patient is likely to be greater than 20% noncompliant in taking study medications

• Patients with chronic medical conditions

• Patients with unstable doses of medications

• Pregnant or lactating women, women intending to become pregnant

• Patient is currently receiving prescription therapy with statins or other lipid-altering medications

• Patient with Type 1 or Type 2 diabetes mellitus that is poorly controlled, newly diagnosed, or is taking new or recently adjusted antidiabetic pharmacotherapy (with the exception of +/- 10 units of insulin)

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Organon and Co

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Organon and Co
• ClinicalTrials.gov Identifier: NCT00409773
• Other Study ID Numbers: 0653A-107; 2006_527
• First Posted: Dec 11, 2006
• Last Update Posted: Feb 14, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Metabolic Syndrome; Hypercholesterolemia; Syndrome; Atorvastatin; Simvastatin; Ezetimibe; Calcium

Study Results

Participant Flow

Recruitment Details	Phase III First Patient In 06-Feb-2007:; Last Patient Last Visit 16-Jul-2008 110 centers worldwide (International, 12 countries) Eligible patients include drug-naïve patients or patients rendered naïve with the appropriate prior washout at moderately high or high risk for coronary heart disease.
Pre-assignment Detail	Patients were randomized to 1 of 5 treatment groups: ezetimibe/simvastatin combination tablet or atorvastatin alone for 6 weeks stratified according to their baseline risk category stratum (high risk patients with atherosclerotic vascular disease or high risk patients without atherosclerotic vascular disease and moderately high risk patients).

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Period Title: Overall Study
STARTED	229	229	229	228	228
COMPLETED	220	222	220	216	218
NOT COMPLETED	9	7	9	12	10

Baseline Characteristics

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg	Total
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks	Total of all reporting groups
Overall Participants	229	229	229	228	228	1143
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	59.7	59.7	58.2	59.5	58.4	59.1
Sex: Female, Male (Count of Participants)
Female	97 42.4%	87 38%	106 46.3%	104 45.6%	104 45.6%	498 43.6%
Male	132 57.6%	142 62%	123 53.7%	124 54.4%	124 54.4%	645 56.4%
Race/Ethnicity, Customized (participants) [Number]
Asian	17 7.4%	15 6.6%	15 6.6%	18 7.9%	21 9.2%	86 7.5%
Black	13 5.7%	18 7.9%	18 7.9%	12 5.3%	14 6.1%	75 6.6%
Other	27 11.8%	27 11.8%	19 8.3%	27 11.8%	26 11.4%	126 11%
White	172 75.1%	169 73.8%	177 77.3%	171 75%	167 73.2%	856 74.9%

Outcome Measures

1. Primary Outcome

Title	Percent Change From Baseline in Low Density Lipoprotein (LDL-C) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	215	219	215	217	217
Least Squares Mean (95% Confidence Interval) [Percent Change]	-36.5	-49.6	-39.4	-53.9	-46.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Reported p-value is multiplicity-adjusted. Hochberg procedure was used to adjust for multiple comparisons.
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-13.1
	Confidence Interval	() 95%; -16.5 to -9.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Reported p-value is multiplicity-adjusted. Hochberg procedure was used to adjust for multiple comparisons.
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.2
	Confidence Interval	() 95%; -13.6 to -6.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	Reported p-value is multiplicity-adjusted. Hochberg procedure was used to adjust for multiple comparisons.
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.0
	Confidence Interval	() 95%; -11.3 to -4.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.7
	Estimation Comments

2. Secondary Outcome

Title	Percent Change From Baseline in Total Cholesterol(mg/dL) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	215	220	216	217	218
Least Squares Mean (95% Confidence Interval) [Percent Change]	-26.5	-33.7	-28.3	-37.3	-32.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.2
	Confidence Interval	() 95%; -9.6 to -4.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.4
	Confidence Interval	() 95%; -7.8 to -2.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-4.4
	Confidence Interval	() 95%; -6.8 to -2.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2
	Estimation Comments

3. Secondary Outcome

Title	Percent Change From Baseline in Triglyceride (TG) (mg/dL) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	215	220	216	217	218
Median (95% Confidence Interval) [Percent Change]	-21.7	-23.3	-27.5	-29.5	-30.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.690
	Comments
	Method	Non-parametric ANOVA
	Comments	ANOVA using normal scores (Tukey method) based on ranks with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.9
	Confidence Interval	() 95%; -5.4 to 3.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.200
	Comments
	Method	Non-parametric ANOVA
	Comments	ANOVA using normal scores (Tukey method) based on ranks with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	2.8
	Confidence Interval	() 95%; -1.6 to 7.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.480
	Comments
	Method	Non-parametric ANOVA
	Comments	ANOVA using normal scores (Tukey method) based on ranks with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.4
	Confidence Interval	() 95%; -4.7 to 3.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percent Change From Baseline in High Density Lipoprotein Cholesterol (HDL-C) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	215	219	216	217	217
Least Squares Mean (95% Confidence Interval) [Percent Change]	3.4	6.8	5.6	8.8	4.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.4
	Confidence Interval	() 95%; 0.7 to 6.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.378
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.2
	Confidence Interval	() 95%; -1.5 to 3.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	4.0
	Confidence Interval	() 95%; 1.3 to 6.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.3
	Estimation Comments

5. Secondary Outcome

Title	Percent Change From Baseline in Non- High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	215	219	216	217	217
Least Squares Mean (95% Confidence Interval) [Percent Change]	-33.5	-43.8	-36.5	-48.3	-41.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.3
	Confidence Interval	() 95%; -13.3 to -7.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.3
	Confidence Interval	() 95%; -10.2 to -4.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.5
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.9
	Confidence Interval	() 95%; -9.9 to -3.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.5
	Estimation Comments

6. Secondary Outcome

Title	Percent Change From Baseline in Very Low Density Lipoprotein Cholesterol (VLDL-C) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	215	217	209	214	216
Least Squares Mean (95% Confidence Interval) [Percent Change]	-17.7	-18.3	-21.6	-23.4	-22.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.809
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.6
	Confidence Interval	() 95%; -5.7 to 4.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.6
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.217
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3.2
	Confidence Interval	() 95%; -1.9 to 8.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.6
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.796
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.7
	Confidence Interval	() 95%; -5.8 to 4.4
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.6
	Estimation Comments

7. Secondary Outcome

Title	Percent Change From Baseline in Apolipoprotein- B (Apo-B) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	211	218	213	214	216
Least Squares Mean (95% Confidence Interval) [Percent Change]	-27.9	-37.2	-31.9	-41.1	-35.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.4
	Confidence Interval	() 95%; -12.1 to -6.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.3
	Confidence Interval	() 95%; -8.1 to -2.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.3
	Confidence Interval	() 95%; -8.0 to -2.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments

8. Secondary Outcome

Title	Percent Change From Baseline in Apolipoprotein-A1 (Apo-A1) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	211	219	213	214	216
Least Squares Mean (95% Confidence Interval) [Percent Change]	0.8	3.2	1.0	3.0	1.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.042
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.4
	Confidence Interval	() 95%; 0.1 to 4.8
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	2.2
	Confidence Interval	() 95%; -0.2 to 4.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.6
	Confidence Interval	() 95%; -7.0 to 4.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.2
	Estimation Comments

9. Secondary Outcome

Title	Percent Change From Baseline in Total-Cholesterol: High Density Lipoprotein-Cholesterol (Total-C:HDL- C) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	215	219	216	217	217
Least Squares Mean (95% Confidence Interval) [Percent Change]	-28.1	-36.9	-31.5	-41.2	-35.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.8
	Confidence Interval	() 95%; -11.6 to -6.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.3
	Confidence Interval	() 95%; -8.2 to -2.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.9
	Confidence Interval	() 95%; -8.7 to -3.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.4
	Estimation Comments

10. Secondary Outcome

Title	Percent Change From Baseline in Low Density Lipoprotein Cholesterol: High Density Lipoprotein Cholesterol (LDL-C: HDL-C) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	215	219	215	217	217
Least Squares Mean (95% Confidence Interval) [Percent Change]	-37.8	-51.8	-42.1	-56.6	-48.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-14.0
	Confidence Interval	() 95%; -17.6 to -10.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-9.7
	Confidence Interval	() 95%; -13.2 to -6.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.5
	Confidence Interval	() 95%; -12.0 to -4.9
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8
	Estimation Comments

11. Secondary Outcome

Title	Percent Change From Baseline in Apolipoprotein-B: Apolipoprotein-A1 (Apo-B:Apo-A1) at Week 6
Time Frame	Baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	211	218	213	214	216
Least Squares Mean (95% Confidence Interval) [Percent Change]	-27.4	-38.4	-32.0	-41.9	-36.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-11.0
	Confidence Interval	() 95%; -14.0 to -8.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-6.4
	Confidence Interval	() 95%; -9.4 to -3.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.5
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.7
	Confidence Interval	() 95%; -8.7 to -2.7
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.5
	Estimation Comments

12. Secondary Outcome

Title	Percent Change From Baseline in Non-High Density Lipoprotein Cholesterol: High Density Lipoprotein Cholesterol (Non-HDL-C:HDL-C) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	215	219	216	217	217
Least Squares Mean (95% Confidence Interval) [Percent Change]	-34.7	-46.2	-39.2	-51.2	-43.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-11.5
	Confidence Interval	() 95%; -15.0 to -8.1
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.0
	Confidence Interval	() 95%; -10.4 to -3.6
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANOVA
	Comments	ANOVA with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.7
	Confidence Interval	() 95%; -11.2 to -4.3
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.8
	Estimation Comments

13. Secondary Outcome

Title	Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 6 in Patients With Atherosclerotic Vascular Disease (AVD)
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	64	71	59	61	63
Least Squares Mean (95% Confidence Interval) [Percent Change]	-37.1	-48.7	-36.9	-56.1	-45.8

14. Secondary Outcome

Title	Percent Change From Baseline in Low Density Lipoprotein Cholesterol (LDL-C) at Week 6 in Patients Without Atherosclerotic Vascular Disease (AVD)
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	151	148	156	156	154
Least Squares Mean (95% Confidence Interval) [Percent Change]	-36.3	-50.1	-40.3	-53.2	-46.1

15. Secondary Outcome

Title	Percent Change From Baseline in High-Sensitivity C-reactive (Hs-CRP) (mg/dL) at Week 6
Time Frame	Baseline and 6 Weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): The FAS population includes all randomized patients who took at least 1 dose of study medication and had a baseline (BL) value and at least one post BL value. Post BL measurements up to 3 days following the last dose of double-blind study medication were included in the analysis.

Arm/Group Title	Atorva 10 mg	EZ/Simva 10 mg/20 mg	Atorva 20mg	EZ/Simva 10 mg/40 mg	Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg	Atorvastatin 20 mg once daily for 6 weeks	Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg	Atorvastatin 40 mg once daily for 6 weeks
Measure Participants	216	218	210	216	215
Median (95% Confidence Interval) [Percent Change]	-16.8	-17.2	-22.4	-27.6	-30.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Atorva 10 mg, EZ/Simva 10 mg/20 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.420
	Comments
	Method	Non-parametric ANOVA
	Comments	ANOVA using normal scores (Tukey method) based on ranks with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-2.9
	Confidence Interval	() 95%; -11.0 to 5.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/20 mg, Atorva 20mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.555
	Comments
	Method	Non-parametric ANOVA
	Comments	ANOVA using normal scores (Tukey method) based on ranks with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	-0.9
	Confidence Interval	() 95%; -9.5 to 7.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	EZ/Simva 10 mg/40 mg, Atorva 40 mg
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.410
	Comments
	Method	Non-parametric ANOVA
	Comments	ANOVA using normal scores (Tukey method) based on ranks with terms for treatment and baseline risk stratum
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	2.3
	Confidence Interval	() 95%; -5.1 to 9.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Atorva 10 mg		EZ/Simva 10 mg/20 mg		Atorva 20mg		EZ/Simva 10 mg/40 mg		Atorva 40 mg
Arm/Group Description	Atorvastatin 10 mg once daily for 6 weeks		Ezetimibe (+) simvastatin combination tablet at doses of 10/20 mg		Atorvastatin 20 mg once daily for 6 weeks		Ezetimibe (+) simvastatin combination tablet at doses of 10/40 mg		Atorvastatin 40 mg once daily for 6 weeks
All Cause Mortality
	Atorva 10 mg		EZ/Simva 10 mg/20 mg		Atorva 20mg		EZ/Simva 10 mg/40 mg		Atorva 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Atorva 10 mg		EZ/Simva 10 mg/20 mg		Atorva 20mg		EZ/Simva 10 mg/40 mg		Atorva 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/ (NaN)		0/ (NaN)		1/ (NaN)		1/ (NaN)		4/ (NaN)
Cardiac disorders
Acute Myocardial Infarction	1/228 (0.4%)		0/226 (0%)		0/226 (0%)		0/224 (0%)		0/224 (0%)
Atrial Fibrillation	1/228 (0.4%)		0/226 (0%)		0/226 (0%)		0/224 (0%)		0/224 (0%)
Atrioventricular Block Second Degree	0/228 (0%)		0/226 (0%)		0/226 (0%)		1/224 (0.4%)		0/224 (0%)
Sick Sinus Syndrome	0/228 (0%)		0/226 (0%)		1/226 (0.4%)		0/224 (0%)		0/224 (0%)
Tachyarrhythmia	0/228 (0%)		0/226 (0%)		0/226 (0%)		0/224 (0%)		1/224 (0.4%)
Hepatobiliary disorders
Cholestasis	0/228 (0%)		0/226 (0%)		0/226 (0%)		0/224 (0%)		1/224 (0.4%)
Infections and infestations
Urinary Tract Infection	0/228 (0%)		0/226 (0%)		1/226 (0.4%)		0/224 (0%)		0/224 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate Cancer	0/228 (0%)		0/226 (0%)		0/226 (0%)		0/224 (0%)		1/224 (0.4%)
Nervous system disorders
Cerebrovascular Accident	0/228 (0%)		0/226 (0%)		0/226 (0%)		0/224 (0%)		1/224 (0.4%)
Headache	1/228 (0.4%)		0/226 (0%)		0/226 (0%)		0/224 (0%)		0/224 (0%)
Ischaemic Cerebral Infarction	1/228 (0.4%)		0/226 (0%)		0/226 (0%)		0/224 (0%)		0/224 (0%)
Other (Not Including Serious) Adverse Events
	Atorva 10 mg		EZ/Simva 10 mg/20 mg		Atorva 20mg		EZ/Simva 10 mg/40 mg		Atorva 40 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/ (NaN)		14/ (NaN)		22/ (NaN)		13/ (NaN)		13/ (NaN)
Gastrointestinal disorders
Any Gastrointestinal Disorders	7/228 (3.1%)		6/226 (2.7%)		7/226 (3.1%)		4/224 (1.8%)		2/224 (0.9%)
Abdominal Tenderness	1/228 (0.4%)		2/226 (0.9%)		3/226 (1.3%)		1/224 (0.4%)		0/224 (0%)
Diarrhoea	5/228 (2.2%)		1/226 (0.4%)		3/226 (1.3%)		1/224 (0.4%)		1/224 (0.4%)
Nausea	1/228 (0.4%)		3/226 (1.3%)		1/226 (0.4%)		2/224 (0.9%)		1/224 (0.4%)
General disorders
Any General Disorders And Administration Site Conditions	2/228 (0.9%)		2/226 (0.9%)		2/226 (0.9%)		1/224 (0.4%)		0/224 (0%)
Fatigue	2/228 (0.9%)		2/226 (0.9%)		2/226 (0.9%)		1/224 (0.4%)		0/224 (0%)
Infections and infestations
Any Infections and Infestations	1/228 (0.4%)		1/226 (0.4%)		2/226 (0.9%)		2/224 (0.9%)		1/224 (0.4%)
Nasopharyngitis	1/228 (0.4%)		1/226 (0.4%)		2/226 (0.9%)		2/224 (0.9%)		1/224 (0.4%)
Musculoskeletal and connective tissue disorders
Any Musculoskeletal And Connective Tissue Disorders	8/228 (3.5%)		7/226 (3.1%)		9/226 (4%)		5/224 (2.2%)		7/224 (3.1%)
Arthralgia	3/228 (1.3%)		1/226 (0.4%)		1/226 (0.4%)		2/224 (0.9%)		1/224 (0.4%)
Back Pain	0/228 (0%)		2/226 (0.9%)		0/226 (0%)		3/224 (1.3%)		2/224 (0.9%)
Muscle Spasms	2/228 (0.9%)		2/226 (0.9%)		3/226 (1.3%)		0/224 (0%)		1/224 (0.4%)
Myalgia	3/228 (1.3%)		2/226 (0.9%)		3/226 (1.3%)		0/224 (0%)		3/224 (1.3%)
Pain In Extremity	3/228 (1.3%)		1/226 (0.4%)		2/226 (0.9%)		1/224 (0.4%)		1/224 (0.4%)
Nervous system disorders
Any Nervous System Disorders	4/228 (1.8%)		2/226 (0.9%)		4/226 (1.8%)		3/224 (1.3%)		2/224 (0.9%)
Dizziness	0/228 (0%)		2/226 (0.9%)		0/226 (0%)		3/224 (1.3%)		0/224 (0%)
Headache	4/228 (1.8%)		0/226 (0%)		4/226 (1.8%)		0/224 (0%)		2/224 (0.9%)
Vascular disorders
Any Vascular Disorders	2/228 (0.9%)		0/226 (0%)		0/226 (0%)		0/224 (0%)		2/224 (0.9%)
Hypertension	2/228 (0.9%)		0/226 (0%)		0/226 (0%)		0/224 (0%)		0/224 (0%)

Limitations/Caveats

15 patients were randomized but not treated. Since these patients were not treated no Adverse Event Data was collected.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Merck agreements may vary with individual investigators, but will not prohibit any investigator from publishing. Merck supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.