Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery

• Sponsor: Vanderbilt University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00791648
• Collaborator: (none)
• Enrollment: 653
• Location: 1
• Arms: 2
• Duration (Months): 65
• Patients Per Site Per Month: 10

Study Details

Study Description

Brief Summary

Aim1a: Statin naive patient's scheduled for cardiac surgery will be randomized to 80mg atorvastatin or placebo on the day prior to surgery and then 40mg daily thereafter until hospital discharge to test the hypothesis that short-term atorvastatin use decreases:

1. acute kidney injury following cardiac surgery.

2. postoperative delirium following cardiac surgery.

Aim1b: Patients using statins preoperatively will be randomized to atorvastatin 80mg or placebo on day of surgery and 40mg or placebo on postop day 1 with resumption of preoperative statin therapy on postop day 2 to test the hypothesis that short-term atorvastatin use decreases:

1. acute kidney injury following cardiac surgery.

2. postoperative delirium following cardiac surgery.

Endpoints include glomerular filtration, urine and plasma markers of renal dysfunction, markers of oxidative stress, mitochondrial function, systemic inflammatory markers, delirium, dialysis, stroke, myocardial infarction, time to extubation, ICU length of stay, and death.

Condition or Disease	Intervention/Treatment	Phase
Acute Kidney Injury; Post-Operative Delirium; Icu Delirium; Acute Renal Failure; Delirium	Drug: atorvastatin; Drug: placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 653 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Short-term Atorvastatin's Effect on Acute Kidney Injury Following Cardiac Surgery
• Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: statin Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	Drug: atorvastatin; Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.; Other Names: Lipitor
Placebo Comparator: placebo Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.	Drug: placebo; Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Acute Kidney Injury [postoperative day 2]

2. Number of Participants With Delirium [while in ICU (about 2 days)]

Secondary Outcome Measures

1. Number of Participants Requiring Dialysis [while in ICU (about 2 days)]

2. Liver Enzyme: Aspartate Aminotransferase Level [postoperative day 1]

3. Number of Participants With Stroke [while in ICU (about 2 days)]

4. Number of Participants That Died [until postoperative hospital discharge (about 7 days)]

5. Mitochondrial Function--mtDNA Copy Number [anesthesia induction and POD 1]

   mtDNA copy number

6. Mitochondrial Function--lactate / Pyruvate Ratio [anesthesia induction, after CPB, and POD 1]

   lactate / pyruvate ratio

7. Mitochondrial Function--PGC-1alpha RNA Expression [anesthesia induction and POD 1]

   PGC-1alpha RNA expression

8. Urine Markers of Renal Injury [anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and Post op Day (POD) 1, 2, 3]

   tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7

9. Plasma Markers of Oxidative Stress: f2-Isoprostanes [anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.]

10. Plasma Markers of Oxidative Stress: Isofurans [anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.]

11. Urine Markers of Oxidative Stress: f2-Isoprostanes [anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.]

12. Urine Markers of Oxidative Stress: Isofurans [anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.]

13. Plasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1) [anesthesia induction, ICU admission, and POD 1]

    measurements of neuronal injury (ubiquitin C-terminal hydrolase-1)

14. Plasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B) [anesthesia induction, ICU admission, and POD 1]

    measurements of blood brain barrier disruption (S100 calcium-binding protein B)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• open heart surgery

Exclusion Criteria:

• acute coronary syndrome with troponin leak or unrelenting angina

• liver dysfunction (transaminases 2x normal)

• history of myopathy or liver dysfunction on prior statin therapy

• use of potent CYP3A4 inhibitors such as antifungal azoles, macrolide antibiotics, HIV protease inhibitors, and nefazodone.

• pregnancy or breast feeding

• cyclosporine use

• dialysis

• history of kidney transplant

• fibrate users who cannot stop fibrate use.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37212

Sponsors and Collaborators

• Vanderbilt University Medical Center

Investigators

• Principal Investigator: Frederic T. Billings, IV, MD, Vanderbilt University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Frederic T Billings IV, Assistant Professor of Anesthesiology and Critical Care Medicine, Vanderbilt University Medical Center
• ClinicalTrials.gov Identifier: NCT00791648
• Other Study ID Numbers: 081238
• First Posted: Nov 14, 2008
• Last Update Posted: Sep 16, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Frederic T Billings IV, Assistant Professor of Anesthesiology and Critical Care Medicine, Vanderbilt University Medical Center: aki; delirium; statin; short-term; cardiac
• Additional relevant MeSH terms: Delirium; Acute Kidney Injury; Wounds and Injuries; Atorvastatin

Study Results

Participant Flow

Pre-assignment Detail	36 patients consented patients were excluded prior to randomization 14 withdrew, 12 did not require surgery, 4 had unreported baseline live dysfunction, 2 developed acute coronary syndrome, 2 had statin intolerance, 1 died prior to study intervention and surgery, 1 enrolled in another drug study.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Period Title: Overall Study
STARTED	308	309
COMPLETED	308	307
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	Statin	Placebo	Total
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.	Total of all reporting groups
Overall Participants	308	307	615
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	66	67	66
Sex: Female, Male (Count of Participants)
Female	94 30.5%	94 30.6%	188 30.6%
Male	214 69.5%	213 69.4%	427 69.4%
Region of Enrollment (participants) [Number]
United States	308 100%	307 100%	615 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Acute Kidney Injury
Time Frame	postoperative day 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	308	307
Count of Participants [Participants]	64 20.8%	60 19.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Statin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.75
	Comments
	Method	Pearson x2
	Comments

2. Primary Outcome

Title	Number of Participants With Delirium
Time Frame	while in ICU (about 2 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	308	307
Count of Participants [Participants]	69 22.4%	75 24.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Statin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.56
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Secondary Outcome

Title	Number of Participants Requiring Dialysis
Time Frame	while in ICU (about 2 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	308	307
Count of Participants [Participants]	5 1.6%	3 1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Statin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.71
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Secondary Outcome

Title	Liver Enzyme: Aspartate Aminotransferase Level
Time Frame	postoperative day 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	308	307
Median (95% Confidence Interval) [units/liter]	49	52

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Statin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.11
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Number of Participants With Stroke
Time Frame	while in ICU (about 2 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	308	307
Count of Participants [Participants]	10 3.2%	7 2.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Statin
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.06
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Number of Participants That Died
Time Frame	until postoperative hospital discharge (about 7 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	308	307
Count of Participants [Participants]	4 1.3%	1 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Statin, Placebo
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	.39
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Mitochondrial Function--mtDNA Copy Number
Description	mtDNA copy number
Time Frame	anesthesia induction and POD 1

Outcome Measure Data

Analysis Population Description

This marker was only measured in a subset of the total study population, chosen at random.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	164	168
at anesthesia induction	0.40	.48
POD 1	0.3	0.43

8. Secondary Outcome

Title	Mitochondrial Function--lactate / Pyruvate Ratio
Description	lactate / pyruvate ratio
Time Frame	anesthesia induction, after CPB, and POD 1

Outcome Measure Data

Analysis Population Description

This marker was only measured in a subset of the total study population, chosen at random.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	80	82
at anesthesia induction	0.04	0.04
after CPB	0.06	0.06
POD 1	0.04	0.04

9. Secondary Outcome

Title	Mitochondrial Function--PGC-1alpha RNA Expression
Description	PGC-1alpha RNA expression
Time Frame	anesthesia induction and POD 1

Outcome Measure Data

Analysis Population Description

This marker was only measured in a subset of the total study population, chosen at random.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	79	76
at anesthesia induction	0.54	0.84
POD 1	1.02	1.37

10. Secondary Outcome

Title	Urine Markers of Renal Injury
Description	tissue inhibitor metaloproteinase-2 x insulin-like growth factor binding protein-7
Time Frame	anesthesia induction, 30 minutes into cardiopulm bypass (CPB), after CPB, ICU admission, 6 hours postop, and Post op Day (POD) 1, 2, 3

Outcome Measure Data

Analysis Population Description

This marker was only measured in a subset of the total study population, chosen at random.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	200	200
at anesthesia induction	0.119	0.098
30 minutes into cardiopulmonary bypass (CPB)	0.171	0.169
after CPB	0.218	0.219
ICU admission	0.096	0.112
6 hours post-op	0.210	0.207
POD 1	0.189	0.186
POD 2	0.170	0.115
POD 3	0.134	0.102

11. Secondary Outcome

Title	Plasma Markers of Oxidative Stress: f2-Isoprostanes
Time Frame	anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.

Outcome Measure Data

Analysis Population Description

This marker was only measured in a subset of the total study population, chosen at random.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	200	200
at anesthesia induction	29.4	28.8
30 minutes into cardiopulmonary bypass (CPB)	41.6	39
after CPB	32.3	31.5
ICU admission	32.1	31.6
6 hours post-op	32.1	41
POD 1	28.1	30.2
POD 2	28.5	37
POD 3	32.7	26.5

12. Secondary Outcome

Title	Plasma Markers of Oxidative Stress: Isofurans
Time Frame	anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.

Outcome Measure Data

Analysis Population Description

This marker was only measured in a subset of the total study population, chosen at random.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	200	200
at anesthesia induction	45	48.4
30 minutes into cardiopulmonary bypass (CPB)	59.9	56.2
after CPB	57.6	60.6
ICU admission	63.7	64
6 hours post-op	42.5	40.4
POD 1	48	50.9
POD 2	40	36
POD 3	33.5	38

13. Secondary Outcome

Title	Urine Markers of Oxidative Stress: f2-Isoprostanes
Time Frame	anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.

Outcome Measure Data

Analysis Population Description

This marker was only measured in a subset of the total study population, chosen at random.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	178	179
at anesthesia induction	1.369	1.478
30 minutes into cardiopulmonary bypass (CPB)	1.750	2.29
after CPB	2.71	2.729
ICU admission	1.816	2.9
6 hours post-op	1.464	1.77
POD 1	1.056	1.143
POD 2	0.792	0.88
POD 3	0.870	0.875

14. Secondary Outcome

Title	Urine Markers of Oxidative Stress: Isofurans
Time Frame	anesthesia induction, 30 minutes into cardiopulmonary bypass (CPB), after CPB, ICU admission, 6 hours postop, and POD 1, 2, 3.

Outcome Measure Data

Analysis Population Description

This marker was only measured in a subset of the total study population, chosen at random.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	178	178
at anesthesia induction	2.146	2.146
30 minutes into cardiopulmonary bypass (CPB)	2.48	2.48
after CPB	3.709	3.709
ICU admission	3.734	3.734
6 hours post-op	3.310	3.070
POD 1	2.344	2.344
POD 2	2.2	2.2
POD 3	2.16	2.16

15. Secondary Outcome

Title	Plasma Markers of Inflammation: Measurements of Neuronal Injury (Ubiquitin C-terminal Hydrolase-1)
Description	measurements of neuronal injury (ubiquitin C-terminal hydrolase-1)
Time Frame	anesthesia induction, ICU admission, and POD 1

Outcome Measure Data

Analysis Population Description

This marker was only measured in a subset of the total study population, chosen at random.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	200	200
at anesthesia induction	6.2	6.7
ICU admission	12.3	11.6
POD 1	12.8	12.2

16. Secondary Outcome

Title	Plasma Markers of Inflammation: Blood Brain Barrier Disruption (S100 Calcium-binding Protein B)
Description	measurements of blood brain barrier disruption (S100 calcium-binding protein B)
Time Frame	anesthesia induction, ICU admission, and POD 1

Outcome Measure Data

Analysis Population Description

This marker was only measured in a subset of the total study population, chosen at random.

Arm/Group Title	Statin	Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.	placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
Measure Participants	200	200
at anesthesia induction	17.5	17
ICU admission	163.9	163.1
POD 1	46.1	45

Adverse Events

Time Frame	First 10 post-op days
Arm/Group Title	Statin		Placebo
Arm/Group Description	atorvastatin: Aim1 intervention: atorvastatin 80mg 1 day prior to open heart surgery and 40mg daily thereafter until hospital discharge. Aim2 intervention: atorvastatin 80mg the day of cardiac surgery and 40mg on postop day 1.		placebo: Aim 1 control: placebo one day prior to cardiac surgery and daily thereafter until hospital discharge. Aim 2 control: placebo the day of cardiac surgery and postop day 1.
All Cause Mortality
	Statin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Statin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/308 (4.5%)		19/307 (6.2%)
Blood and lymphatic system disorders
Hemolytic Anemia	0/308 (0%)	0	1/307 (0.3%)	1
Coagulapathy	0/308 (0%)	0	1/307 (0.3%)	1
Idiopathic Thrombocytopenia Purpura	1/308 (0.3%)	1	0/307 (0%)	0
Cardiac disorders
Cardiac Arrest	5/308 (1.6%)	5	2/307 (0.7%)	2
Severe Heart Failure	1/308 (0.3%)	1	0/307 (0%)	0
Congenital, familial and genetic disorders
Cardiac Tamponade	0/308 (0%)	0	1/307 (0.3%)	1
Gastrointestinal disorders
Ileus	0/308 (0%)	0	1/307 (0.3%)	1
Small Bowel Obstruction	0/308 (0%)	0	1/307 (0.3%)	1
Infections and infestations
Severe Infection	2/308 (0.6%)	2	4/307 (1.3%)	4
Injury, poisoning and procedural complications
Fall with Factured Hip	0/308 (0%)	0	1/307 (0.3%)	1
Intra-operative Injury to Blood Vessel	1/308 (0.3%)	1	0/307 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hemothorax	1/308 (0.3%)	1	1/307 (0.3%)	1
Severe Respiratory Distress	2/308 (0.6%)	2	1/307 (0.3%)	1
Aspiration	0/308 (0%)	0	2/307 (0.7%)	2
Skin and subcutaneous tissue disorders
Sternal Dehiscence	0/308 (0%)	0	2/307 (0.7%)	2
Vascular disorders
Severe Peripheral Vascular Ischemia	1/308 (0.3%)	1	1/307 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Statin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	308/308 (100%)		307/307 (100%)
Cardiac disorders
Tachycardia	49/308 (15.9%)	215	42/307 (13.7%)	190
Hypotension	188/308 (61%)	1032	192/307 (62.5%)	1073
Vasoplegia	120/308 (39%)	342	118/307 (38.4%)	357
Decreased Cardiac Output	187/308 (60.7%)	643	194/307 (63.2%)	623
Lactic Acidosis	55/308 (17.9%)	194	59/307 (19.2%)	202
Hepatobiliary disorders
Transaminemia	23/308 (7.5%)	29	39/307 (12.7%)	46
Infections and infestations
Fever	50/308 (16.2%)	125	52/307 (16.9%)	117
Leukocytosis	141/308 (45.8%)	513	140/307 (45.6%)	522
Surgical and medical procedures
Anemia	183/308 (59.4%)	1608	172/307 (56%)	1537

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.