Effects of Atorvastatin on Endothelial Progenitor Cells After Coronary Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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Assessment of the Effects of Atorvastatin on Endothelial Progenitor Cells After Coronary ByPass Surgery; A Randomized Controlled Trial

Conditions
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Coronary Artery Bypass Surgery, Elective Surgical Procedure

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atorvastatin<br>Hydroxymethylglutaryl-CoA Reductase Inhibitors | Drug: Atorvastatin<br>* 40mg/day once daily for two weeks prior to surgery<br>* Other names: Ator;|
| Placebo Comparator: Placebo<br>Atorvastatin like pill | Drug: Placebo<br>* 1tb/day once daily for two weeks prior to surgery<br>* Other names: Placebo tablets matched to atorvastatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Progenitor Cells (EPCs) Count (Cells/µl) |  | Postoperative 6th hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | 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 | 
| High Sensitive C-reactive Protein (hsCRP mg/L) |  | 5 days postoperatively | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endothelial progenitor cells, Atorvastatin, Coronary surgery