Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT01988571
• Collaborator: National Cancer Institute (NCI) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 279
• Locations: 51
• Arms: 2
• Actual Duration (Months): 79.7
• Patients Per Site: 5.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this research study is to see if Atorvastatin (Lipitor) 40 mg by mouth daily decreases the chance of developing heart problems in individuals receiving adjuvant anthracycline-based chemotherapy for breast cancer of lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Lymphoma	Drug: Atorvastatin; Drug: Placebo	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

Specific Aim 1:

To determine if Atorvastatin(Lipitor) administration preserves left ventricular ejection fraction (LVEF) 24 months after initiation of Anthracycline-based adjuvant therapy for adjuvant treatment of breast cancer or lymphoma.

Specific Aim 2:

To determine if baseline to 6-month differences in LVEF predict baseline to 24-month differences in LVEF after Anthracycline-based adjuvant therapy and concomitant atorvastatin therapy.

To achieve these aims, we will perform a double-blind, placebo-controlled, randomized clinical trial of 0 or 40 mg of atorvastatin/day in 278 individuals scheduled to receive Anthracycline-based chemotherapy for treatment of Stage I-III breast cancer or lymphoma Stage I-IV with a projected > 2 year life expectancy. We will use innovative noninvasive magnetic resonance imaging (MRI) procedures to accurately measure LVEF. In addition, we will measure left ventricle (LV) volumes, myocardial strain, fibrosis, aortic pulse wave velocity (PWV) and wall thickness, all factors that can influence LVEF by altering LV pre-load, after-load, and contractility.19,20 Advanced serum biomarkers will be measured that assess for the presence of oxidative/nitrosative stress, systemic inflammation and circulating neurohormones that also may influence LVEF.

This study will test a new clinical paradigm to manage breast cancer: primary prevention of Anthracycline-based adjuvant therapy-related LV dysfunction using pre-treatment with low-cost statins. In addition, this trial will be the first systematic collection of data regarding the mechanism(s) and time course by which LV dysfunction and subsequent chronic heart failure (CHF) evolve in individuals given Anthracycline-based chemotherapy for breast cancer or lymphoma. These data will be useful to physicians trying to determine the optimal cardiac protection strategies when administering adjuvant chemotherapeutic regimens to their breast cancer or lymphoma patients. The objective of this research is to use inexpensive medications to preserve cardiovascular (CV) health and thereby improve overall survival in the growing number of breast cancer and lymphoma patients.

SECONDARY OBJECTIVES

Specific Aim 1:

To document the effect of Atorvastatin (Lipitor) on cognitive function using a battery of neurocognitive tests (HVLT, Rey-osterrieth Figure, controlled oral word association test (COWA), Trail-making Parts A and B, Digit Span and Grooved Pegboard) in breast cancer and lymphoma patients receiving an anthracycline.

Specific Aim 2:

To document the effect of Atorvastatin(Lipitor) on self-reported quality of life using validated questionnaires (PROMIS including: General form, Cog Concerns, Cog Abilities, Fatigue, Pain intensity and interference, Sleep Disturbance, Physical Functioning and Social Functioning) in breast cancer and lymphoma patients receiving an anthracycline.

Study Design

• Study Type: Interventional
• Actual Enrollment: 279 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Preventing Anthracycline Cardiovascular Toxicity With Statins (PREVENT)
• Actual Study Start Date: Feb 1, 2014
• Actual Primary Completion Date: Sep 24, 2020
• Actual Study Completion Date: Sep 24, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 - Atorvastatin One 40 mg Atorvastatin tablet each morning by mouth for 24 months	Drug: Atorvastatin; 40 mg tablet taken by mouth each morning for 24 months.; Other Names: Lipitor
Placebo Comparator: Arm 2 - Placebo One placebo tablet each morning by mouth for 24 months.	Drug: Atorvastatin; 40 mg tablet taken by mouth each morning for 24 months.; Other Names: Lipitor ; Drug: Placebo; One placebo tablet taken each morning orally for 24 months.; Other Names: sugar pill

Outcome Measures

Primary Outcome Measures

1. Left Ventricular Ejection Fraction (LVEF) [24 months]

   24 month estimated values of clinical measurements obtained from Cardiac MRI left ventricular ejection fraction by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

Secondary Outcome Measures

1. End Diastolic Volume [24 months]

   24 month estimated values of clinical measurements obtained from Cardiac MRI End Diastolic Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

2. End Systolic Volume [24 months]

   24 month estimated values of clinical measurements obtained from Cardiac MRI End Systolic Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

3. Stroke Volume [24 months]

   24 month estimated values of clinical measurements obtained from Cardiac MRI Stroke Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

4. Left Ventricular (LV) Mass [24 months]

   24 month estimated values of clinical measurements obtained from Cardiac MRI left ventricular mass by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

5. Pulse Wave Velocity [24 months]

   24 month estimated values of clinical measurements obtained from Cardiac MRI pulse wave velocity by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.

6. Hopkins Verbal Learning Test (HVLT) Total Recall [24 months]

   24 month estimated values Hopkins Verbal Learning test (HVLT) total recall by group. Linear model adjusts for baseline value and group assignment. No missing imputation performed. Ranges from 0 to 36 and higher numbers reflect better recall.

7. Controlled Oral Word Association (COWA) [24 months]

   24 month estimated values Controlled Oral Word Association (COWA) by group. Linear model adjusts for baseline value and group assignment. No missing imputation performed. The COWA uses the three letter set of C, F, and L to assess phonemic fluency. Individuals are given 1 min to name as many words as possible beginning with one of the letters. The procedure is then repeated for the remaining two letters. Ranges from 0 to the total number of correct words that begin with one of the letters in the set. There is no ceiling of a maximum score. Higher numbers reflect better verbal fluency.

8. Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Applied Cognition - General Concerns - Short Form 4a [24 months]

   Patient reported quality of life outcomes obtained from patient-reported outcomes measurement (PROMIS) questionnaire - Applied Cognition - General Concerns - Short Form 4a . Scores range from 4-20 and then adjusted by t-scores ranging from 30.1-63.8. Higher scores reflect better cognition. Linear models include baseline assessment and group and multiple imputation was utilized.

9. Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Fatigue Short Form 41 [24 months]

   Patient reported quality of life outcomes obtained from patient-reported outcomes measurement (PROMIS) questionnaire - Fatigue Short Form 41. Scores range from 4-20 and then adjusted by t-scores ranging from 33.7-75.8. Higher scores reflect worse fatigue. Linear models include baseline assessment and group and multiple imputation was utilized.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Stage I-III breast cancer (including inflammatory and newly diagnosed recurrent breast cancer) or lymphoma Stage I-IV. (Patients should have a > 2 year life expectancy)

• Scheduled to receive adjuvant chemotherapy with an Anthracycline (doxorubicin and epirubicin)

• 21 years of age or older

• LVEF > 50% (Most recent within the last 5 years)

• Prior administration of anthracyclines is acceptable if therapy was completed > 6 months prior to study enrollment

• Patients that are receiving or have received chemotherapy regimens are allowed

• Able to hold breath for 10 seconds

• Prior cancers allowed if no evidence of disease in last 5 years

• Eastern Cooperative Oncology Group (ECOG) 0 or 1

Exclusion Criteria:

• Prior use of lipid-lowering therapy within the last 6 months

• Current postmenopausal hormone-replacement therapy

• Uncontrolled hypertension (systolic blood pressure >190 mm Hg or diastolic blood pressure >100 mm Hg)

• Scheduled to receive neoadjuvant chemotherapy with an anthracycline

• No active liver disease allowed

• Uncontrolled hypothyroidism

• Recent history (within past 3 years) of alcohol or drug abuse, inflammatory conditions such as lupus or inflammatory bowel disease, use of immunosuppressant agents, or another medical condition that might compromise safety or the successful completion of the study.

• Patients with ferromagnetic cerebral aneurysm clips or other intraorbital/intracranial metal;pacemakers, defibrillators, functioning neurostimulator devices or other implanted electronic devices.

• Unstable angina; significant ventricular arrhythmias (>20 premature ventricular complexes (PVCs)/min due to gating difficulty) atrial fibrillation with uncontrolled ventricular response; coronary artery disease; acute myocardial infarction within 28 days

• Current use of Cytochrome P450 (CYP3A4) inhibitors. These include Clarithromycin, HIV protease inhibitors, Itraconazole, grapefruit juice, Cyclosporine, Rifampin or Digoxin

• Current or history of hepatic dysfunction

• Unable to provide informed consent

• Claustrophobia

• Planning to move within 24 months of trial enrollment

• Pregnant or breast-feeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kaiser Permanente Los Angeles Medical Center	Los Angeles	California	United States	90027
2	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
3	MedStar Washington Hospital Center	Washington	District of Columbia	United States	20010
4	Northwestern University	Chicago	Illinois	United States	60611
5	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637
6	Cancer Center of Kansas-Wichita Medical Arts Tower	Wichita	Kansas	United States	67208
7	Cancer Center of Kansas - Wichita	Wichita	Kansas	United States	67214
8	Ochsner Medical Center Jefferson	New Orleans	Louisiana	United States	70121
9	Tufts Medical Center	Boston	Massachusetts	United States	02111
10	Spectrum Health at Butterworth Campus	Grand Rapids	Michigan	United States	49503
11	William Beaumont Hospital-Royal Oak	Royal Oak	Michigan	United States	48073
12	William Beaumont Hospital - Troy	Troy	Michigan	United States	48085
13	Saint John's Hospital - Healtheast	Maplewood	Minnesota	United States	55109
14	Abbott-Northwestern Hospital	Minneapolis	Minnesota	United States	55407
15	Mayo Clinic in Rochester	Rochester	Minnesota	United States	55905
16	Park Nicollet Clinic - Saint Louis Park	Saint Louis Park	Minnesota	United States	55416
17	Regions Hospital	Saint Paul	Minnesota	United States	55101
18	United Hospital	Saint Paul	Minnesota	United States	55102
19	Mission Hospital	Asheville	North Carolina	United States	28801
20	Hope Women's Cancer Centers-Asheville	Asheville	North Carolina	United States	28816
21	Cone Health Cancer Center at Alamance Regional	Burlington	North Carolina	United States	27215
22	Novant Health Presbyterian Medical Center	Charlotte	North Carolina	United States	28204
23	Oncology Specialists of Charlotte	Charlotte	North Carolina	United States	28207
24	Cone Health Cancer Center	Greensboro	North Carolina	United States	27403
25	Novant Health Cancer Institute - Huntersville	Huntersville	North Carolina	United States	28078
26	Southern Oncology Specialists-Huntersville	Huntersville	North Carolina	United States	28078
27	Novant Health Cancer Institute - Kernersville	Kernersville	North Carolina	United States	27284
28	Novant Health Cancer Specialists-Matthews	Matthews	North Carolina	United States	28105
29	Novant Health Forsyth Medical Center	Winston-Salem	North Carolina	United States	27103
30	Novant Health Oncology Specialists	Winston-Salem	North Carolina	United States	27103
31	Wake Forest University Health Sciences	Winston-Salem	North Carolina	United States	27157
32	Columbus Oncology and Hematology Associates Inc	Columbus	Ohio	United States	43214
33	Doctors Hospital	Columbus	Ohio	United States	43228
34	Delaware Health Center-Grady Cancer Center	Delaware	Ohio	United States	43015
35	Genesis Healthcare System Cancer Care Center	Zanesville	Ohio	United States	43701
36	Geisinger Medical Center	Danville	Pennsylvania	United States	17822
37	University of Pennsylvania/Abramson Cancer Center	Philadelphia	Pennsylvania	United States	19104
38	Medical University of South Carolina	Charleston	South Carolina	United States	29425
39	Prisma Health Cancer Institute - Easley	Easley	South Carolina	United States	29640
40	Prisma Health Cancer Institute - Butternut	Greenville	South Carolina	United States	29605
41	Prisma Health Cancer Institute - Faris	Greenville	South Carolina	United States	29605
42	Prisma Health Cancer Institute - Eastside	Greenville	South Carolina	United States	29615
43	Prisma Health Cancer Institute - Seneca	Seneca	South Carolina	United States	29672
44	Centra Lynchburg Hematology-Oncology Clinic Inc	Lynchburg	Virginia	United States	24501
45	Virginia Cancer Institute	Richmond	Virginia	United States	23230
46	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
47	Shenandoah Oncology PC	Winchester	Virginia	United States	22601
48	Aurora Cancer Care-Southern Lakes VLCC	Burlington	Wisconsin	United States	53105
49	Aurora Cancer Care-Grafton	Grafton	Wisconsin	United States	53024
50	Vince Lombardi Cancer Clinic - Oshkosh	Oshkosh	Wisconsin	United States	54904
51	Aurora Medical Center in Summit	Summit	Wisconsin	United States	53066

Sponsors and Collaborators

• Wake Forest University Health Sciences
• National Cancer Institute (NCI)
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Gregory Hundley, MD, Wake Forest University Health Sciences

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 27, 2020
• Informed Consent Form - Feb 1, 2018

More Information

Publications

None provided.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01988571
• Other Study ID Numbers: IRB00038639; U10CA081851; 1R01HL118740-01; REBACCCWFU 98213; NCI-2013-01760
• First Posted: Nov 20, 2013
• Last Update Posted: Jan 4, 2022
• Last Verified: Dec 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Wake Forest University Health Sciences: Stage I breast cancer; Stage II breast cancer; Stage III breast cancer; Stage I Lymphoma; Stage II Lymphoma; Stage III Lymphoma; Stage IV Lymphoma
• Additional relevant MeSH terms: Lymphoma; Breast Neoplasms; Atorvastatin

Study Results

Participant Flow

Pre-assignment Detail	No reason for exclusion prior to randomization.

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Period Title: Overall Study
STARTED	139	140
Completed Baseline	136	139
Completed 6 Month Visit	122	126
COMPLETED	100	105
NOT COMPLETED	39	35

Baseline Characteristics

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo	Total
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.	Total of all reporting groups
Overall Participants	139	140	279
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	48.5 (12.5)	49.4 (11.5)	49.0 (12.0)
Sex: Female, Male (Count of Participants)
Female	129 92.8%	127 90.7%	256 91.8%
Male	10 7.2%	13 9.3%	23 8.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 2.9%	4 2.9%	8 2.9%
Not Hispanic or Latino	134 96.4%	136 97.1%	270 96.8%
Unknown or Not Reported	1 0.7%	0 0%	1 0.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	2 1.4%	1 0.7%	3 1.1%
Native Hawaiian or Other Pacific Islander	4 2.9%	0 0%	4 1.4%
Black or African American	16 11.5%	22 15.7%	38 13.6%
White	115 82.7%	116 82.9%	231 82.8%
More than one race	1 0.7%	1 0.7%	2 0.7%
Unknown or Not Reported	1 0.7%	0 0%	1 0.4%
Medicare (Count of Participants)
Count of Participants [Participants]	16 11.5%	10 7.1%	26 9.3%
Medicaid (Count of Participants)
Count of Participants [Participants]	10 7.2%	11 7.9%	21 7.5%
Private Insurance (Count of Participants)
Count of Participants [Participants]	112 80.6%	121 86.4%	233 83.5%
No Health Insurance (Count of Participants)
Count of Participants [Participants]	6 4.3%	1 0.7%	7 2.5%
Cancer Type (Count of Participants)
Lymphoma	20 14.4%	21 15%	41 14.7%
Breast Cancer	119 85.6%	119 85%	238 85.3%
Cancer Stage (Count of Participants)
Stage 1	24 17.3%	22 15.7%	46 16.5%
Stage 2	77 55.4%	77 55%	154 55.2%
Stage 3	34 24.5%	40 28.6%	74 26.5%
Stage 4	4 2.9%	1 0.7%	5 1.8%
Marital Status (Count of Participants)
Single, Never Married	23 16.5%	15 10.7%	38 13.6%
Married	82 59%	84 60%	166 59.5%
Living in a married like relationship	4 2.9%	8 5.7%	12 4.3%
Separated or Divorced	23 16.5%	25 17.9%	48 17.2%
Widowed	3 2.2%	3 2.1%	6 2.2%
Unknown	4 2.9%	5 3.6%	9 3.2%
Education (Count of Participants)
Grades 1-8	2 1.4%	0 0%	2 0.7%
Grades 9-11	3 2.2%	3 2.1%	6 2.2%
High School/GED	28 20.1%	16 11.4%	44 15.8%
Vocational/trading school	4 2.9%	6 4.3%	10 3.6%
Some College/Assoicates	27 19.4%	49 35%	76 27.2%
College Degree (Bachelors)	36 25.9%	32 22.9%	68 24.4%
Some post college	6 4.3%	7 5%	13 4.7%
Masters degree	21 15.1%	16 11.4%	37 13.3%
Doctoral degree	1 0.7%	3 2.1%	4 1.4%
Unknown	11 7.9%	8 5.7%	19 6.8%
Income (Count of Participants)
Less than $10,000	11 7.9%	6 4.3%	17 6.1%
$10,000-$20,000	14 10.1%	12 8.6%	26 9.3%
$20,000-$35,000	12 8.6%	19 13.6%	31 11.1%
$35,000-$50,000	15 10.8%	12 8.6%	27 9.7%
$50,000-$75,000	27 19.4%	30 21.4%	57 20.4%
$75,000-$100,000	11 7.9%	16 11.4%	27 9.7%
$100,000-$150,000	10 7.2%	10 7.1%	20 7.2%
More than $150,000	7 5%	5 3.6%	12 4.3%
Unknown	32 23%	30 21.4%	62 22.2%
Job Status (Count of Participants)
Not currently working	16 11.5%	14 10%	30 10.8%
Retired	15 10.8%	14 10%	29 10.4%
Homemaker	10 7.2%	4 2.9%	14 5%
Employed	83 59.7%	95 67.9%	178 63.8%
Disabled, unable to work	7 5%	7 5%	14 5%
Other	5 3.6%	3 2.1%	8 2.9%
Unknown	3 2.2%	3 2.1%	6 2.2%
Body Mass Index (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	29 (6.43)	31 (7.4)	30 (7.0)

Outcome Measures

1. Primary Outcome

Title	Left Ventricular Ejection Fraction (LVEF)
Description	24 month estimated values of clinical measurements obtained from Cardiac MRI left ventricular ejection fraction by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All those with baseline and 24 month cardiac MRI (multiple imputation utilized for missing data).

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Measure Participants	136	139
Least Squares Mean (Standard Error) [percent ejected from LV per heartbeat]	58.1 (0.555)	57.9 (0.560)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1 - Atorvastatin, Arm 2 - Placebo
	Comments	Linear models adjusting for baseline values and utilized multiple imputation for missing data.
	Type of Statistical Test	Superiority
	Comments	Power described in protocol.
Statistical Test of Hypothesis	p-Value	0.84
	Comments
	Method	ANCOVA
	Comments	Adjusted for multiple imputation of missing data
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.1608
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.7787
	Estimation Comments

2. Secondary Outcome

Title	End Diastolic Volume
Description	24 month estimated values of clinical measurements obtained from Cardiac MRI End Diastolic Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All those with baseline and 24 month cardiac MRI (multiple imputation utilized for missing data).

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Measure Participants	136	139
Least Squares Mean (Standard Error) [milliliters of blood]	123 (2.06)	125 (2.01)

3. Secondary Outcome

Title	End Systolic Volume
Description	24 month estimated values of clinical measurements obtained from Cardiac MRI End Systolic Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All those with baseline and 24 month cardiac MRI (multiple imputation utilized for missing data).

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Measure Participants	136	139
Least Squares Mean (Standard Error) [milliliters of blood]	51.8 (1.27)	52.9 (1.25)

4. Secondary Outcome

Title	Stroke Volume
Description	24 month estimated values of clinical measurements obtained from Cardiac MRI Stroke Volume by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All those with baseline and 24 month cardiac MRI (multiple imputation utilized for missing data).

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Measure Participants	136	139
Least Squares Mean (Standard Error) [milliliters per minute]	71 (1.58)	72.2 (1.50)

5. Secondary Outcome

Title	Left Ventricular (LV) Mass
Description	24 month estimated values of clinical measurements obtained from Cardiac MRI left ventricular mass by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All those with baseline and 24 month cardiac MRI (multiple imputation utilized for missing data).

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Measure Participants	136	139
Least Squares Mean (Standard Error) [gram per meter squared]	88.4 (1.68)	87.5 (1.65)

6. Secondary Outcome

Title	Pulse Wave Velocity
Description	24 month estimated values of clinical measurements obtained from Cardiac MRI pulse wave velocity by group. Linear model adjusts for baseline value and group assignment and multiple imputation was utilized for missing data.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

All those with baseline and 24 month cardiac MRI (multiple imputation utilized for missing data).

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Measure Participants	136	139
Least Squares Mean (Standard Error) [m/s]	5.73 (0.247)	5.51 (0.24)

7. Secondary Outcome

Title	Hopkins Verbal Learning Test (HVLT) Total Recall
Description	24 month estimated values Hopkins Verbal Learning test (HVLT) total recall by group. Linear model adjusts for baseline value and group assignment. No missing imputation performed. Ranges from 0 to 36 and higher numbers reflect better recall.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Those with data available at baseline and 24 months.

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Measure Participants	136	139
Least Squares Mean (Standard Error) [score on a scale]	28.5 (0.518)	27.5 (0.503)

8. Secondary Outcome

Title	Controlled Oral Word Association (COWA)
Description	24 month estimated values Controlled Oral Word Association (COWA) by group. Linear model adjusts for baseline value and group assignment. No missing imputation performed. The COWA uses the three letter set of C, F, and L to assess phonemic fluency. Individuals are given 1 min to name as many words as possible beginning with one of the letters. The procedure is then repeated for the remaining two letters. Ranges from 0 to the total number of correct words that begin with one of the letters in the set. There is no ceiling of a maximum score. Higher numbers reflect better verbal fluency.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Those with data available at baseline and 24 months.

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Measure Participants	136	139
Least Squares Mean (Standard Error) [score on a scale]	41.6 (1.07)	44.7 (1.06)

9. Secondary Outcome

Title	Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Applied Cognition - General Concerns - Short Form 4a
Description	Patient reported quality of life outcomes obtained from patient-reported outcomes measurement (PROMIS) questionnaire - Applied Cognition - General Concerns - Short Form 4a . Scores range from 4-20 and then adjusted by t-scores ranging from 30.1-63.8. Higher scores reflect better cognition. Linear models include baseline assessment and group and multiple imputation was utilized.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Those with baseline and 24 month assessment completed. Multiple imputation was utilized for missing data.

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Measure Participants	136	139
Least Squares Mean (Standard Error) [t-score]	45.57 (1.1)	46.55 (1.14)

10. Secondary Outcome

Title	Patient-reported Outcomes Measurement (PROMIS) Questionnaire - Fatigue Short Form 41
Description	Patient reported quality of life outcomes obtained from patient-reported outcomes measurement (PROMIS) questionnaire - Fatigue Short Form 41. Scores range from 4-20 and then adjusted by t-scores ranging from 33.7-75.8. Higher scores reflect worse fatigue. Linear models include baseline assessment and group and multiple imputation was utilized.
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

Those with baseline and 24 month assessment completed. Multiple imputation was utilized for missing data.

Arm/Group Title	Arm 1 - Atorvastatin	Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.	One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
Measure Participants	136	139
Least Squares Mean (Standard Error) [t-score]	48.17 (1.08)	49.29 (1.12)

Adverse Events

Time Frame	Adverse events were collected during the entire trial and up to 30 days post-completion of statin or placebo (approximately 25 months)
Adverse Event Reporting Description	Serious Adverse Event reporting begins after the informed consent is signed. Serious Adverse Events occurring within 30 days of study completion must be reported via FDA Form 3500 (MedWatch).
Arm/Group Title	Arm 1 - Atorvastatin		Arm 2 - Placebo
Arm/Group Description	One 40 mg Atorvastatin tablet each morning by mouth for 24 months Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months.		One placebo tablet each morning by mouth for 24 months. Atorvastatin: 40 mg tablet taken by mouth each morning for 24 months. Placebo: One placebo tablet taken each morning orally for 24 months.
All Cause Mortality
	Arm 1 - Atorvastatin		Arm 2 - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/139 (2.2%)		1/140 (0.7%)
Serious Adverse Events
	Arm 1 - Atorvastatin		Arm 2 - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/139 (12.2%)		18/140 (12.9%)
Blood and lymphatic system disorders
White blood cells decreased	0/139 (0%)		1/140 (0.7%)
Cardiac disorders
Cardiac Disorder	0/139 (0%)		1/140 (0.7%)
Gastrointestinal disorders
Abdominal Pain	1/139 (0.7%)		0/140 (0%)
Diarrhea	1/139 (0.7%)		0/140 (0%)
Dysphagia	1/139 (0.7%)		0/140 (0%)
Infections and infestations
Febrile neutropenia	3/139 (2.2%)		7/140 (5%)
Herpes simplex reactivation	1/139 (0.7%)		1/140 (0.7%)
Meningitis	0/139 (0%)		1/140 (0.7%)
Breast Infection	1/139 (0.7%)		0/140 (0%)
Upper respiratory infection	1/139 (0.7%)		0/140 (0%)
Injury, poisoning and procedural complications
Back Pain	1/139 (0.7%)		0/140 (0%)
Investigations
Decreased neutophils	1/139 (0.7%)		1/140 (0.7%)
Metabolism and nutrition disorders
Dehydration	1/139 (0.7%)		2/140 (1.4%)
Nervous system disorders
Nervous System Disorder	1/139 (0.7%)		0/140 (0%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	0/139 (0%)		2/140 (1.4%)
Atelectasis	1/139 (0.7%)		0/140 (0%)
Surgical and medical procedures
Hospitalization for Reconstructive Surgery	3/139 (2.2%)		2/140 (1.4%)
Other (Not Including Serious) Adverse Events
	Arm 1 - Atorvastatin		Arm 2 - Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/139 (0%)		0/140 (0%)

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.