Coronary Artery Bypass Surgery, Elective Surgical Procedure
Conditions
Keywords
Endothelial progenitor cells, Atorvastatin, Coronary surgery
Brief summary
Experimental data have demonstrated favourable effects of statins on endothelial progenitor cell (EPC) mobilization from the bone marrow, and cardiac homing. The purpose of the present prospective randomized controlled trial is to determine the effects of aggressive atorvastatin treatment (40 mg daily 2-weeks prior to surgery) on the number of endothelial progenitor cells (EPCs) after cardiopulmonary bypass by comparing with placebo.
Detailed description
Endothelial progenitor cells, a subgroup of hematopoietic stem cells have a significant role in vascular homeostasis. In animal models of ischemia, endothelial progenitor cells are rapidly incorporated into sites of neovascularization, have the potential to induce and augment vasculogenesis/ angiogenesis, prevent cardiomyocyte apoptosis in peri-infarct regions, and reduce adverse remodeling. Treatment with atorvastatin has been shown to increase endothelial progenitor cell count in patients with coronary artery disease. Therefore, we will investigate whether atorvastatin augments the number of endothelial progenitor cells after cardiopulmonary bypass in patients undergoing coronary artery bypass surgery (CABG). Thus, we conducted a randomized double-blind, placebo-controlled, 2-way parallel trial in 60 patients undergoing coronary artery bypass surgery. Patients will receive either 2-week treatment with atorvastatin or placebo prior to surgery. Endothelial progenitor cells will be quantitated by flow cytometric phenotyping obtained from peripheral blood samples. In addition, cardiac markers (CK-MB mass, cardiac troponin-I), biochemical profile, liver function tests, high sensitive C-reactive protein (hsCRP) and coagulation profile will be determined at 4 time points: 1) preoperatively (baseline); 2) 6 hours after the end of cardiopulmonary bypass; 3) 24 hours after surgery; 4) 5th days postoperatively. Clinical, operative characteristics, cardiac markers, high sensitive C-reactive protein and endothelial progenitor cell count will be compared between the groups. Adverse outcomes will also be noted and reported.
Interventions
DRUGAtorvastatin
40mg/day once daily for two weeks prior to surgery
DRUGPlacebo
1tb/day once daily for two weeks prior to surgery
Sponsors
Turkish Society of Hematology
Ankara University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patients undergoing elective isolated coronary artery bypass surgery with on-pump technique * Written informed consent
Exclusion criteria
* Concomitant valve or aortic surgery * Left ventricular aneurysm repair * Re-operation * Emergency surgery * History of myocardial infarction within less than 4 weeks * Hepatic impairment * Chronic renal impairment * Drug related side effects (allergy or hypersensitivity) * Familial Hyperlipidemia * Autoimmune conditions which require steroids
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Endothelial Progenitor Cells (EPCs) Count (Cells/µl) | Postoperative 6th hours |
Secondary
| Measure | Time frame |
|---|---|
| Left Ventricular Ejection Fraction (LVEF %) Measured at 30 Days Postoperatively | Change between statin and placebo groups at 30 days postoperatively |
| High Sensitive C-reactive Protein (hsCRP mg/L) | Postoperative 6th hours |
Countries
Turkey (Türkiye)
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Atorvastatin Hydroxymethylglutaryl-CoA Reductase Inhibitors
Atorvastatin : 40mg/day once daily for two weeks prior to surgery | 30 |
| Placebo Atorvastatin like pill
Placebo : 1tb/day once daily for two weeks prior to surgery | 30 |
| Total | 60 |
Baseline characteristics
| Characteristic | Placebo | Atorvastatin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 9 Participants | 8 Participants | 17 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants | 22 Participants | 43 Participants |
| Age, Continuous | 62.2 years STANDARD_DEVIATION 8.1 | 60.8 years STANDARD_DEVIATION 8.6 | 61.6 years STANDARD_DEVIATION 8.4 |
| Region of Enrollment Turkey | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 18 Participants | 19 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 29 |
| serious Total, serious adverse events | 1 / 30 | 2 / 29 |
Outcome results
Primary
Endothelial Progenitor Cells (EPCs) Count (Cells/µl)
Time frame: Postoperative 6th hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Endothelial Progenitor Cells (EPCs) Count (Cells/µl) | 5.00 cells/µl | Standard Error 0.06 |
| Placebo | Endothelial Progenitor Cells (EPCs) Count (Cells/µl) | 2.19 cells/µl | Standard Error 0.06 |
Secondary
High Sensitive C-reactive Protein (hsCRP mg/L)
Time frame: Postoperative 6th hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | High Sensitive C-reactive Protein (hsCRP mg/L) | 72.9 mg/L | Standard Error 0.6 |
| Placebo | High Sensitive C-reactive Protein (hsCRP mg/L) | 96.0 mg/L | Standard Error 0.7 |
Secondary
High Sensitive C-reactive Protein (hsCRP mg/L)
Time frame: 5 days postoperatively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | High Sensitive C-reactive Protein (hsCRP mg/L) | 4.3 mg/L | Standard Error 0.2 |
| Placebo | High Sensitive C-reactive Protein (hsCRP mg/L) | 11.4 mg/L | Standard Error 0.8 |
Secondary
Left Ventricular Ejection Fraction (LVEF %) Measured at 30 Days Postoperatively
Time frame: Change between statin and placebo groups at 30 days postoperatively
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atorvastatin | Left Ventricular Ejection Fraction (LVEF %) Measured at 30 Days Postoperatively | 54.3 percentage of LVEF | Standard Deviation 7.5 |
| Placebo | Left Ventricular Ejection Fraction (LVEF %) Measured at 30 Days Postoperatively | 53.2 percentage of LVEF | Standard Deviation 8.7 |