A phase3 Study Measuring the Effect of Rosuvastatin 20 mg on Carotid Intima-Media Thickness in Chinese Subjects With Subclinical Atherosclerosis

• Sponsor: AstraZeneca (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02546323
• Collaborator: (none)
• Enrollment: 543
• Locations: 24
• Arms: 2
• Actual Duration (Months): 40.4
• Patients Per Site: 22.6
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effects of of rosuvastatin 20 mg compared to placebo for treating Chinese patients with subclinical atherosclerosis.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: Rosuvastatin; Drug: Placebo	Phase 3

Detailed Description

This study is a randomized, double-blind, placebo-controlled, multicenter parallel group study assessing the effects of rosuvastatin 20 mg treatment for 104 weeks on the change in intimamedia thickness (IMT) of the common carotid artery (CCA), carotid bulb, and internal carotid artery (ICA) in adult Chinese subjects with subclinical atherosclerosis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 543 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Placebo-controlled, Multicenter Parallel Group Phase 3 Study Measuring the Effect of Rosuvastatin 20 mg on Carotid Intima-Media Thickness in Chinese Subjects
• Actual Study Start Date: Sep 17, 2015
• Actual Primary Completion Date: Jan 29, 2019
• Actual Study Completion Date: Jan 29, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Rosuvastatin 20 mg tablets, Daily oral dose	Drug: Rosuvastatin; 20mg tablets, orally once daily for the duration of the 104-week treatment period; Other Names: Crestor
Placebo Comparator: Placebo Matching placebo tablets	Drug: Placebo; Matching placebo tablets, orally once daily for the duration of the 104-week treatment period.

Outcome Measures

Primary Outcome Measures

1. Annualized Rate of Change in Mean of the Maximum (MeanMax) CIMT Measurements From Each of the 12 Carotid Artery Sites Based on All Scans Performed During the 104-Week Study Period [From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).]

   CIMT measurements were made from ultrasound images of the common carotid artery (CCA), carotid bulb and internal carotid artery (ICA). The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. Twelve carotid artery sites were scanned at each visit and the 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for a specific segment. The annualized rate of change in the MeanMax CIMT measurements from each of the 12 sites, based on all scans performed during the study, was determined using a multi-level linear mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.

Secondary Outcome Measures

1. Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left CCA [From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).]

   CIMT measurements were made from ultrasound images of the near and far walls of the right and left CCA. The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. The 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for this segment. The annualized rate of change in the MeanMax CIMT measurements, based on all scans performed during the study, was determined using a multi-level linear mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.

2. Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left Carotid Bulb [From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).]

   CIMT measurements were made from ultrasound images of the near and far walls of the right and left carotid bulb. The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. The 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for this segment. The annualized rate of change in the MeanMax CIMT measurements, based on all scans performed during the study, was determined using a multi-level linear mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.

3. Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left ICA [From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).]

   CIMT measurements were made from ultrasound images of the near and far walls of the right and left ICA. The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. The 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for this segment. The annualized rate of change in the MeanMax CIMT measurements, based on all scans performed during the study, was determined using a multi-level mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.

4. Annualized Rate of Change in the Mean of the Mean (MeanMean) CIMT of the Near and Far Walls of the Right and Left CCA [From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).]

   CIMT measurements were made from ultrasound images of the near and far walls of the right and left CCA. The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. The 3 images recorded at the 3 interrogation angles were measured to determine the mean of the CIMT for this segment. The annualized rate of change in the MeanMean CIMT measurements, based on all scans performed during the study, was determined using a multi-level mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.

5. Percent Change From Baseline in Lipid, Lipoprotein and Apolipoprotein Values at Final Visit: Last Observation Carried Forward (LOCF) [From baseline (Week 0) to end-of-study (Week 104).]

   The percent change from baseline at final visit for lipid and lipoprotein measurements (low-density lipoprotein cholesterol [LDL-C], total cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C, non-HDL-C/HDL-C ratio) and apolipoprotein measurements (apolipoprotein A-I [ApoA-I], apolipoprotein B [ApoB] and ApoB/ApoA-I ratio) was determined by analysis of covariance (ANCOVA) with treatment as a fixed effect and baseline value as a covariate. In the evaluation of change from baseline (Week 0) to the final visit at Week 104, any missing observations were imputed by LOCF.

6. Percent Change From Baseline in Lipid and Lipoprotein Values at Final Visit: Time Weighted Average [From baseline (Week 0) to end-of-study (Week 104).]

   The percent change from baseline at final visit for lipid and lipoprotein measurements (LDL-C, total cholesterol, HDL-C, triglycerides, non-HDL-C, non-HDL-C/HDL-C ratio) was determined by ANCOVA with treatment as a fixed effect and baseline value as a covariate. In the evaluation of change from baseline (Week 0), the time-weighted average value was calculated as the value multiplied by the number of days since the last assessment, summed for all observations, and divided by the sum of days between all visits.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provision of informed consent prior to any study-specific procedures

• Male aged ≥45 and <70 years or female aged ≥55 and <70 years

• Subjects with only hypertension (as defined blood pressure ≥140/90 mmHg or on antihypertensive treatment) and age as CVD risk factors and subjects without hypertension who have 3 or more other risk factors (including age) must have "Fasting LDL C of ≥120 mg/dL (3.1 mmol/L) and <160 mg/dL (4.1mmol/L)"; Subjects without hypertension who have fewer than 3 other risk factors (including age) must have "Fasting LDL-C of ≥120 mg/dL (3.1 mmol/L) and <190 mg/dL (4.9 mmol/L)"

• Triglycerides <500 mg/dL (5.65 mmol/L) at Visit 1

• HDL-C levels ≤60 mg/dL (1.6 mmol/L) at Visit 1

• Maximum IMT ≥1.2 mm and <3.5 mm at any location in the carotid ultrasound scans conducted at both Visit 2 and Visit 3

• Willing to follow all study procedures including study visits, fasting blood draws, and compliance with study treatment regimen

Exclusion Criteria:

• Use of pharmacologic lipid-lowering medications (eg, statins, fibrate derivatives,bile acid binding resins, niacin, or its analogues at doses >400 mg or prescribed Chinese traditional drugs), including cholesterol-absorption inhibitors (CAIs), and CAI/statin combination, within 12 months prior to Visit 1

• Current or recent (within 2 weeks of Visit 1) use of supplements known to alter lipid metabolism (eg, soluble fibers [including >2 teaspoons Metamucil® or psyllium-containing supplement per day] or other dietary fiber supplements, marine oils, sterol/stanol products, or other supplement determined at the discretion of the investigator)

• History of hypersensitivity reactions to other HMG-CoA reductase inhibitors

• Pregnant women, women who are breast-feeding, and women of childbearing potential who are not using chemical or mechanical contraception or who have a positive serum pregnancy test

• Clinical evidence of coronary artery disease (CAD) or any other atherosclerotic disease such as angina, MI, transient ischemic attack, symptomatic CAD, cerebrovascular accident, percutaneous coronary intervention, coronary artery bypass graft, peripheral arterial disease, abdominal aortic aneurysm

• History of cancer (other than basal cell carcinoma) in the past 2 years

• Uncontrolled hypertension defined as either a mean resting diastolic blood pressure of ≥110 mmHg or a resting systolic blood pressure of ≥180 mmHg recorded at any time during the screening period

• History of diabetes mellitus or current diabetes mellitus

• Uncontrolled hypothyroidism defined as a thyroid stimulating hormone (TSH) >1.5 times the upper limit of normal (ULN) at Visit 1 or subjects whose thyroid replacement therapy was initiated within the last 3 months

• History of heterozygous or homozygous familial hypercholesterolemia or known hyperlipoproteinemia Types I, III, IV, or V (familial dysbetalipoproteinemia)

• Use of the disallowed concomitant medications within 12 months prior to Visit 1

• History of alcohol and/or drug abuse within the past 5 years

• Active liver disease or hepatic dysfunction as defined by elevations of ≥1.5 x ULN at Visit 1 in any of the following liver function tests: ALT, AST or bilirubin

• Serum creatine kinase (CK) >3 x ULN at Visit 1

• Serum creatinine >2.0 mg/dL (177 mmol/L) recorded during the screening period

• Participation in another investigational drug study, and having ingested investigational drug ≤4 weeks before enrollment in the screening period

• Previous randomization in the present study

• History of a significant medical or psychological condition that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Beijing		China	100035
2	Research Site	Beijing		China	100050
3	Research Site	Beijing		China	100191
4	Research Site	Beijing		China	100853
5	Research Site	Bengbu		China	233060
6	Research Site	Changsha		China	410011
7	Research Site	Chongqin		China	400042
8	Research Site	Guangzhou		China	510080
9	Research Site	Guangzhou		China	510120
10	Research Site	Guangzhou		China	510260
11	Research Site	Guangzhou		China	510515
12	Research Site	Guangzhou		China	510630
13	Research Site	Haerbin		China	150001
14	Research Site	Nanchang		China	330006
15	Research Site	Nanjing		China	210009
16	Research Site	Ningbo		China	315010
17	Research Site	Shanghai		China	200032
18	Research Site	Shanghai		China	200065
19	Research Site	Shanghai		China	200090
20	Research Site	Shenyang		China	110001
21	Research Site	Tianjin		China	300457
22	Research Site	Wenzhou		China	CN-325000
23	Research Site	Wuhan		China	430022
24	Research Site	Xian		China	710061

Sponsors and Collaborators

• AstraZeneca

Investigators

• Principal Investigator: Yongjun Wang, M.D., Beijing Tian Tan Hospital, Capital Medical University
• Principal Investigator: Yundai Chen, M.D., Chinese PLA General Hospital

Study Documents (Full-Text)

• Study Protocol - Mar 28, 2018
• Statistical Analysis Plan - Mar 6, 2019

More Information

Additional Information:

• redacted protocol
• SAP_redacted

Publications

None provided.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02546323
• Other Study ID Numbers: D3565C00003
• First Posted: Sep 10, 2015
• Last Update Posted: Dec 11, 2019
• Last Verified: Oct 1, 2019

• Keywords provided by AstraZeneca: Rosuvastatin 20 mg treatment, Carotid Intima-Media Thickness, Chinese subjects, Subclinical atherosclerosis
• Additional relevant MeSH terms: Atherosclerosis; Rosuvastatin Calcium

Study Results

Participant Flow

Recruitment Details	Chinese patients with subclinical atherosclerosis and a 10-year ischemic cardiovascular disease (ICVD) risk of less than 10% (as assessed by the 2007 China Adult Dyslipidema Management Guidelines) were enrolled at 25 sites in China between 17 September 2015 and 29 January 2019.
Pre-assignment Detail	Eligible patients with carotid intima-media thickness (CIMT) measurements of maximum CIMT ≥1.2 millimeters (mm) and <3.5 mm were randomized to receive either rosuvastatin 20 milligrams (mg) or corresponding placebo once daily. Randomization was stratified by ICVD risk (<5% or 5% to 10%).

Arm/Group Title	Rosuvastatin 20 mg	Placebo
Arm/Group Description	Rosuvastatin 20 mg was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.	Placebo was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.
Period Title: Overall Study
STARTED	272	271
Received Treatment	272	268
COMPLETED	212	205
NOT COMPLETED	60	66

Baseline Characteristics

Arm/Group Title	Rosuvastatin 20 mg	Placebo	Total
Arm/Group Description	Rosuvastatin 20 mg was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.	Placebo was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.	Total of all reporting groups
Overall Participants	272	271	543
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.0 (5.23)	59.7 (4.96)	59.4 (5.11)
Sex: Female, Male (Count of Participants)
Female	146 53.7%	158 58.3%	304 56%
Male	126 46.3%	113 41.7%	239 44%
Race/Ethnicity, Customized (Number) [Number]
Asian	272 100%	271 100%	543 100%
10-year ICVD Risk (Count of Participants)
<5%	196 72.1%	195 72%	391 72%
≥5% - <10%	76 27.9%	76 28%	152 28%

Outcome Measures

1. Primary Outcome

Title	Annualized Rate of Change in Mean of the Maximum (MeanMax) CIMT Measurements From Each of the 12 Carotid Artery Sites Based on All Scans Performed During the 104-Week Study Period
Description	CIMT measurements were made from ultrasound images of the common carotid artery (CCA), carotid bulb and internal carotid artery (ICA). The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. Twelve carotid artery sites were scanned at each visit and the 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for a specific segment. The annualized rate of change in the MeanMax CIMT measurements from each of the 12 sites, based on all scans performed during the study, was determined using a multi-level linear mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.
Time Frame	From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

Outcome Measure Data

Analysis Population Description

The ITT analysis set consisted of all randomized patients. Patients were analyzed according to the treatment to which they were randomized.

Arm/Group Title	Rosuvastatin 20 mg	Placebo
Arm/Group Description	Rosuvastatin 20 mg was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.	Placebo was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.
Measure Participants	272	271
Mean (Standard Error) [mm/year]	0.0038 (0.00312)	0.0142 (0.00317)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Comparison of annualized rate of change in MeanMax CIMT measurement difference between rosuvastatin 20 mg and placebo.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.020
	Comments	Statistical significance of the MeanMax CIMT annualized rate of change between rosuvastatin 20 mg and placebo was evaluated using time-by-treatment interaction term in the model.
	Method	Multi-level mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Estimated mean difference
	Estimated Value	-0.0103
	Confidence Interval	(2-Sided) 95%; -0.0191 to -0.0016
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.00445
	Estimation Comments	Randomized treatment group, time, time-by-treatment interaction, ICVD risk stratification, carotid artery site, center, age, sex, and scan reader were fixed effects. Random effects were the intercept and slope for individual patients.

2. Secondary Outcome

Title	Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left CCA
Description	CIMT measurements were made from ultrasound images of the near and far walls of the right and left CCA. The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. The 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for this segment. The annualized rate of change in the MeanMax CIMT measurements, based on all scans performed during the study, was determined using a multi-level linear mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.
Time Frame	From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

Outcome Measure Data

Analysis Population Description

The ITT analysis set consisted of all randomized patients. Patients were analyzed according to the treatment to which they were randomized.

Arm/Group Title	Rosuvastatin 20 mg	Placebo
Arm/Group Description	Rosuvastatin 20 mg was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.	Placebo was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.
Measure Participants	272	271
Mean (Standard Error) [mm/year]	-0.0031 (0.00310)	0.0079 (0.00315)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Comparison of annualized rate of change in MeanMax CIMT measurement difference between rosuvastatin 20 mg and placebo.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments	Statistical significance of the MeanMax CIMT annualized rate of change between rosuvastatin 20 mg and placebo was evaluated using time-by-treatment interaction term in the model.
	Method	Multi-level mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Estimated mean difference
	Estimated Value	-0.0110
	Confidence Interval	(2-Sided) 95%; -0.0197 to -0.0024
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.00442
	Estimation Comments	Randomized treatment group, time, time-by-treatment interaction, ICVD risk stratification, carotid artery site, center, age, sex, and scan reader were fixed effects. Random effects were the intercept and slope for individual patients.

3. Secondary Outcome

Title	Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left Carotid Bulb
Description	CIMT measurements were made from ultrasound images of the near and far walls of the right and left carotid bulb. The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. The 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for this segment. The annualized rate of change in the MeanMax CIMT measurements, based on all scans performed during the study, was determined using a multi-level linear mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.
Time Frame	From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

Outcome Measure Data

Analysis Population Description

The ITT analysis set consisted of all randomized patients. Patients were analyzed according to the treatment to which they were randomized.

Arm/Group Title	Rosuvastatin 20 mg	Placebo
Arm/Group Description	Rosuvastatin 20 mg was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.	Placebo was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.
Measure Participants	272	271
Mean (Standard Error) [mm/year]	0.0067 (0.00634)	0.0228 (0.00643)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Comparison of annualized rate of change in MeanMax CIMT measurement difference between rosuvastatin 20 mg and placebo.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.073
	Comments	Statistical significance of the MeanMax CIMT annualized rate of change between rosuvastatin 20 mg and placebo was evaluated using time-by-treatment interaction term in the model.
	Method	Multi-level mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Estimated mean difference
	Estimated Value	-0.0162
	Confidence Interval	(2-Sided) 95%; -0.0339 to 0.0015
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.00903
	Estimation Comments	Randomized treatment group, time, time-by-treatment interaction, ICVD risk stratification, carotid artery site, center, age, sex, and scan reader were fixed effects. Random effects were the intercept and slope for individual patients.

4. Secondary Outcome

Title	Annualized Rate of Change in the MeanMax CIMT of the Near and Far Walls of the Right and Left ICA
Description	CIMT measurements were made from ultrasound images of the near and far walls of the right and left ICA. The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. The 3 images recorded at the 3 interrogation angles were measured to determine the maximum of the CIMT for this segment. The annualized rate of change in the MeanMax CIMT measurements, based on all scans performed during the study, was determined using a multi-level mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.
Time Frame	From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

Outcome Measure Data

Analysis Population Description

The ITT analysis set consisted of all randomized patients. Patients were analyzed according to the treatment to which they were randomized.

Arm/Group Title	Rosuvastatin 20 mg	Placebo
Arm/Group Description	Rosuvastatin 20 mg was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.	Placebo was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.
Measure Participants	272	271
Mean (Standard Error) [mm/year]	0.0077 (0.00502)	0.0120 (0.00511)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Comparison of annualized rate of change in MeanMax CIMT measurement difference between rosuvastatin 20 mg and placebo.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.547
	Comments	Statistical significance of the MeanMax CIMT annualized rate of change between rosuvastatin 20 mg and placebo was evaluated using time-by-treatment interaction term in the model.
	Method	Multi-level mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Estimated mean difference
	Estimated Value	-0.0043
	Confidence Interval	(2-Sided) 95%; -0.0183 to 0.0097
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.00716
	Estimation Comments	Randomized treatment group, time, time-by-treatment interaction, ICVD risk stratification, carotid artery site, center, age, sex, and scan reader were fixed effects. Random effects were the intercept and slope for individual patients.

5. Secondary Outcome

Title	Annualized Rate of Change in the Mean of the Mean (MeanMean) CIMT of the Near and Far Walls of the Right and Left CCA
Description	CIMT measurements were made from ultrasound images of the near and far walls of the right and left CCA. The thickness of the intima and media was determined as the distance from the interface between the vessel lumen and the intima, to the interface between the media and the adventitia. The 3 images recorded at the 3 interrogation angles were measured to determine the mean of the CIMT for this segment. The annualized rate of change in the MeanMean CIMT measurements, based on all scans performed during the study, was determined using a multi-level mixed effects regression model that estimated mean annualized rate of change (mm/year) over the 104-week study period. The model fitted regression lines to profiles of CIMT values consisting of 2 pre-randomization values, 3 values from visits during the treatment period, and 2 end-of-study visits.
Time Frame	From baseline (pre-randomization Week -2 and Week -4) to end-of-study (Week 104).

Outcome Measure Data

Analysis Population Description

The ITT analysis set consisted of all randomized patients. Patients were analyzed according to the treatment to which they were randomized.

Arm/Group Title	Rosuvastatin 20 mg	Placebo
Arm/Group Description	Rosuvastatin 20 mg was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.	Placebo was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.
Measure Participants	272	271
Mean (Standard Error) [mm/year]	-0.0011 (0.00191)	0.0075 (0.00194)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Comparison of annualized rate of change in MeanMean CIMT measurement difference between rosuvastatin 20 mg and placebo
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments	Statistical significance of the MeanMean CIMT annualized rate of change between rosuvastatin 20 mg and placebo was evaluated using time-by-treatment interaction term in the model.
	Method	Multi-level mixed effects model
	Comments
Method of Estimation	Estimation Parameter	Estimated mean difference
	Estimated Value	-0.0086
	Confidence Interval	(2-Sided) 95%; -0.0139 to -0.0032
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.00272
	Estimation Comments	Randomized treatment group, time, time-by-treatment interaction, ICVD risk stratification, carotid artery site, center, age, sex, and scan reader were fixed effects. Random effects were the intercept and slope for individual patients

6. Secondary Outcome

Title	Percent Change From Baseline in Lipid, Lipoprotein and Apolipoprotein Values at Final Visit: Last Observation Carried Forward (LOCF)
Description	The percent change from baseline at final visit for lipid and lipoprotein measurements (low-density lipoprotein cholesterol [LDL-C], total cholesterol, high-density lipoprotein cholesterol [HDL-C], triglycerides, non-HDL-C, non-HDL-C/HDL-C ratio) and apolipoprotein measurements (apolipoprotein A-I [ApoA-I], apolipoprotein B [ApoB] and ApoB/ApoA-I ratio) was determined by analysis of covariance (ANCOVA) with treatment as a fixed effect and baseline value as a covariate. In the evaluation of change from baseline (Week 0) to the final visit at Week 104, any missing observations were imputed by LOCF.
Time Frame	From baseline (Week 0) to end-of-study (Week 104).

Outcome Measure Data

Analysis Population Description

The ITT analysis set consisted of all randomized patients. Patients were analyzed according to the treatment to which they were randomized.

Arm/Group Title	Rosuvastatin 20 mg	Placebo
Arm/Group Description	Rosuvastatin 20 mg was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.	Placebo was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.
Measure Participants	272	271
LDL-C	-26.47 (1.700)	8.99 (1.727)
Total Cholesterol	-20.56 (1.010)	1.29 (1.026)
HDL-C	5.47 (0.944)	0.48 (0.959)
Triglycerides	-7.26 (2.575)	12.38 (2.616)
Non-HDL-C	-27.67 (1.344)	1.82 (1.365)
Non-HDL-C/HDL-C	-28.52 (1.637)	3.23 (1.663)
ApoB	-24.20 (1.307)	1.91 (1.295)
ApoA-I	3.16 (0.784)	0.96 (0.777)
ApoB/ApoA-I	-25.14 (1.450)	1.63 (1.436)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): LDL-C
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-35.46
	Confidence Interval	(2-Sided) 95%; -40.23 to -30.70
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.426
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): total cholesterol
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-21.85
	Confidence Interval	(2-Sided) 95%; -24.68 to -19.02
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.441
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): HDL-C
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	5.0
	Confidence Interval	(2-Sided) 95%; 2.35 to 7.64
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.347
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): Triglycerides
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-19.65
	Confidence Interval	(2-Sided) 95%; -26.86 to -12.44
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 3.671
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): Non-HDL-C
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-29.49
	Confidence Interval	(2-Sided) 95%; -33.25 to -25.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.917
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): Non-HDL-C/HDL-C ratio
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-31.75
	Confidence Interval	(2-Sided) 95%; -36.33 to -27.16
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.334
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): ApoB
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-26.12
	Confidence Interval	(2-Sided) 95%; -29.73 to -22.50
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.840
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): ApoA-I
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.047
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	2.19
	Confidence Interval	(2-Sided) 95%; 0.02 to 4.36
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.104
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): ApoB/ApoA-I ratio
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-26.77
	Confidence Interval	(2-Sided) 95%; -30.78 to -22.76
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.041
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

7. Secondary Outcome

Title	Percent Change From Baseline in Lipid and Lipoprotein Values at Final Visit: Time Weighted Average
Description	The percent change from baseline at final visit for lipid and lipoprotein measurements (LDL-C, total cholesterol, HDL-C, triglycerides, non-HDL-C, non-HDL-C/HDL-C ratio) was determined by ANCOVA with treatment as a fixed effect and baseline value as a covariate. In the evaluation of change from baseline (Week 0), the time-weighted average value was calculated as the value multiplied by the number of days since the last assessment, summed for all observations, and divided by the sum of days between all visits.
Time Frame	From baseline (Week 0) to end-of-study (Week 104).

Outcome Measure Data

Analysis Population Description

The ITT analysis set consisted of all randomized patients. Patients were analyzed according to the treatment to which they were randomized.

Arm/Group Title	Rosuvastatin 20 mg	Placebo
Arm/Group Description	Rosuvastatin 20 mg was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.	Placebo was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.
Measure Participants	272	271
LDL-C	-34.89 (1.275)	4.62 (1.295)
Total Cholesterol	-23.98 (0.798)	1.49 (0.811)
HDL-C	7.07 (0.737)	3.41 (0.748)
Triglycerides	-9.05 (2.091)	9.36 (2.124)
Non-HDL-C	-32.59 (1.072)	1.19 (1.089)
Non-HDL-C/HDL-C	-34.31 (1.288)	-0.38 (1.308)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): LDL-C
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-39.51
	Confidence Interval	(2-Sided) 95%; -43.08 to -35.94
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.819
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): total cholesterol
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-25.46
	Confidence Interval	(2-Sided) 95%; -27.70 to -23.23
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.139
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): HDL-C
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	3.67
	Confidence Interval	(2-Sided) 95%; 1.60 to 5.73
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.051
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): Triglycerides
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-18.41
	Confidence Interval	(2-Sided) 95%; -24.26 to -12.55
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.981
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): Non-HDL-C
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-33.78
	Confidence Interval	(2-Sided) 95%; -36.78 to -30.78
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.529
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Rosuvastatin 20 mg, Placebo
	Comments	Treatment difference (rosuvastatin 20 mg - placebo): Non-HDL-C/HDL-C ratio
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	-33.93
	Confidence Interval	(2-Sided) 95%; -37.54 to -30.32
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.836
	Estimation Comments	Treatment as a fixed effect and baseline value as a covariate.

Adverse Events

Time Frame	Treatment Emergent Adverse Events were collected from day of first dose in Week 0 up to and including 10 days following the date of last dose of investigational product or placebo (up to Week 104).
Adverse Event Reporting Description	The safety analysis set consisted of all patients who took at least 1 dose of investigational product or placebo. Patients were analyzed according to treatment actually received.
Arm/Group Title	Rosuvastatin 20 mg		Placebo
Arm/Group Description	Rosuvastatin 20 mg was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.		Placebo was administered in oral tablet form, once daily, for a 104-week (2-year) treatment period.
All Cause Mortality
	Rosuvastatin 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/272 (0%)		1/268 (0.4%)
Serious Adverse Events
	Rosuvastatin 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/272 (14%)		34/268 (12.7%)
Cardiac disorders
Acute myocardial infarction	0/272 (0%)	0	2/268 (0.7%)	2
Angina unstable	0/272 (0%)	0	1/268 (0.4%)	1
Arrhythmia	1/272 (0.4%)	1	1/268 (0.4%)	1
Arteriosclerosis coronary artery	1/272 (0.4%)	1	2/268 (0.7%)	2
Coronary artery disease	0/272 (0%)	0	1/268 (0.4%)	1
Sinus node dysfunction	0/272 (0%)	0	1/268 (0.4%)	1
Ear and labyrinth disorders
Vertigo positional	1/272 (0.4%)	1	0/268 (0%)	0
Endocrine disorders
Goitre	1/272 (0.4%)	1	1/268 (0.4%)	1
Hyperparathyroidism primary	1/272 (0.4%)	1	0/268 (0%)	0
Thyroid mass	1/272 (0.4%)	1	0/268 (0%)	0
Eye disorders
Cataract	2/272 (0.7%)	3	1/268 (0.4%)	1
Iridocyclitis	1/272 (0.4%)	1	0/268 (0%)	0
Pathologic myopia	1/272 (0.4%)	1	0/268 (0%)	0
Pterygium	0/272 (0%)	0	1/268 (0.4%)	1
Retinal detachment	1/272 (0.4%)	1	0/268 (0%)	0
Retinal vein occlusion	0/272 (0%)	0	1/268 (0.4%)	1
Gastrointestinal disorders
Anal fistula	1/272 (0.4%)	1	0/268 (0%)	0
Gastritis	1/272 (0.4%)	1	0/268 (0%)	0
Haemorrhoids	1/272 (0.4%)	1	0/268 (0%)	0
Large intestine polyp	1/272 (0.4%)	1	1/268 (0.4%)	1
Upper gastrointestinal haemorrhage	0/272 (0%)	0	1/268 (0.4%)	1
General disorders
Pyrexia	1/272 (0.4%)	1	0/268 (0%)	0
Hepatobiliary disorders
Bile duct stone	1/272 (0.4%)	1	0/268 (0%)	0
Cholecystitis acute	1/272 (0.4%)	1	0/268 (0%)	0
Hepatic cyst	0/272 (0%)	0	1/268 (0.4%)	1
Infections and infestations
Chronic sinusitis	0/272 (0%)	0	1/268 (0.4%)	1
Gastroenteritis	0/272 (0%)	0	1/268 (0.4%)	1
Hepatitis viral	0/272 (0%)	0	1/268 (0.4%)	1
Herpes zoster	1/272 (0.4%)	1	0/268 (0%)	0
Infection	1/272 (0.4%)	1	0/268 (0%)	0
Pneumonia	1/272 (0.4%)	1	0/268 (0%)	0
Upper respiratory tract infection	0/272 (0%)	0	1/268 (0.4%)	1
Urinary tract infection	0/272 (0%)	0	1/268 (0.4%)	1
Injury, poisoning and procedural complications
Ankle fracture	1/272 (0.4%)	1	0/268 (0%)	0
Fall	0/272 (0%)	0	1/268 (0.4%)	1
Fracture	0/272 (0%)	0	1/268 (0.4%)	1
Joint dislocation	0/272 (0%)	0	1/268 (0.4%)	1
Joint injury	1/272 (0.4%)	1	0/268 (0%)	0
Lumbar vertebral fracture	0/272 (0%)	0	2/268 (0.7%)	2
Meniscus injury	1/272 (0.4%)	1	0/268 (0%)	0
Patella fracture	1/272 (0.4%)	1	0/268 (0%)	0
Pulmonary contusion	0/272 (0%)	0	1/268 (0.4%)	1
Road traffic accident	1/272 (0.4%)	1	1/268 (0.4%)	1
Traumatic fracture	0/272 (0%)	0	1/268 (0.4%)	1
Investigations
Investigation	1/272 (0.4%)	1	0/268 (0%)	0
Metabolism and nutrition disorders
Type 2 diabetes mellitus	1/272 (0.4%)	1	0/268 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	1/272 (0.4%)	1	0/268 (0%)	0
Osteoarthritis	1/272 (0.4%)	1	2/268 (0.7%)	2
Spinal column stenosis	0/272 (0%)	0	1/268 (0.4%)	1
Spinal osteoarthritis	2/272 (0.7%)	4	0/268 (0%)	0
Spondylolisthesis	1/272 (0.4%)	1	0/268 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer female	0/272 (0%)	0	1/268 (0.4%)	1
Breast cancer metastatic	0/272 (0%)	0	1/268 (0.4%)	1
Colon cancer	0/272 (0%)	0	1/268 (0.4%)	1
Lung neoplasm malignant	1/272 (0.4%)	1	0/268 (0%)	0
Mycosis fungoides	1/272 (0.4%)	1	0/268 (0%)	0
Salivary gland cancer	1/272 (0.4%)	1	0/268 (0%)	0
Salivary gland neoplasm	1/272 (0.4%)	1	0/268 (0%)	0
Thyroid cancer	1/272 (0.4%)	1	0/268 (0%)	0
Nervous system disorders
Cerebral artery stenosis	1/272 (0.4%)	1	0/268 (0%)	0
Cerebral infarction	2/272 (0.7%)	2	0/268 (0%)	0
Cerebral ischaemia	1/272 (0.4%)	1	0/268 (0%)	0
Cerebrovascular accident	1/272 (0.4%)	1	0/268 (0%)	0
Dizziness	1/272 (0.4%)	1	0/268 (0%)	0
Intercostal neuralgia	1/272 (0.4%)	1	0/268 (0%)	0
Renal and urinary disorders
Hypertonic bladder	1/272 (0.4%)	1	0/268 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	1/272 (0.4%)	1	0/268 (0%)	0
Chronic obstructive pulmonary disease	0/272 (0%)	0	1/268 (0.4%)	1
Skin and subcutaneous tissue disorders
Henoch-Schonlein purpura	0/272 (0%)	0	1/268 (0.4%)	1
Vascular disorders
Arterial thrombosis	0/272 (0%)	0	1/268 (0.4%)	1
Hypertension	1/272 (0.4%)	1	1/268 (0.4%)	1
Other (Not Including Serious) Adverse Events
	Rosuvastatin 20 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	144/272 (52.9%)		142/268 (53%)
Gastrointestinal disorders
Toothache	23/272 (8.5%)	39	15/268 (5.6%)	23
Infections and infestations
Nasopharyngitis	52/272 (19.1%)	79	56/268 (20.9%)	77
Upper respiratory tract infection	49/272 (18%)	74	54/268 (20.1%)	71
Investigations
Blood glucose increased	24/272 (8.8%)	24	18/268 (6.7%)	18
Protein urine present	16/272 (5.9%)	16	9/268 (3.4%)	10
Nervous system disorders
Dizziness	14/272 (5.1%)	17	16/268 (6%)	24
Respiratory, thoracic and mediastinal disorders
Cough	14/272 (5.1%)	18	15/268 (5.6%)	19
Vascular disorders
Hypertension	19/272 (7%)	19	21/268 (7.8%)	27

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.