Effects of Atorvastatin on Endothelial Progenitor Cells After Coronary Surgery

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Coronary Artery Bypass Surgery; Elective Surgical Procedure	Drug: Atorvastatin; Drug: Placebo	Phase 4

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	60 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	Assessment of the Effects of Atorvastatin on Endothelial Progenitor Cells After Coronary ByPass Surgery; A Randomized Controlled Trial
Study Start Date :	February 2010
Actual Primary Completion Date :	July 2010
Actual Study Completion Date :	October 2010

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Atorvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors	Drug: Atorvastatin; 40mg/day once daily for two weeks prior to surgery; Other Name: Ator
Placebo Comparator: Placebo; Atorvastatin like pill	Drug: Placebo; 1tb/day once daily for two weeks prior to surgery; Other Name: Placebo tablets matched to atorvastatin

Outcome Measures

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Primary Outcome Measures :

1. Endothelial Progenitor Cells (EPCs) Count (Cells/µl) [ Time Frame: Postoperative 6th hours ]

Secondary Outcome Measures :

1. Left Ventricular Ejection Fraction (LVEF %) Measured at 30 Days Postoperatively [ Time Frame: Change between statin and placebo groups at 30 days postoperatively ]
2. High Sensitive C-reactive Protein (hsCRP mg/L) [ Time Frame: Postoperative 6th hours ]
3. High Sensitive C-reactive Protein (hsCRP mg/L) [ Time Frame: 5 days postoperatively ]

Eligibility Criteria

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Ages Eligible for Study:	30 Years to 75 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

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Locations

Turkey
Ankara University Medical Faculty, Department of Cardiovascular Surgery
Ankara, Cebeci, Turkey, 06340

Sponsors and Collaborators

Ankara University

Turkish Society of Hematology

Investigators

Study Director:	RUCHAN AKAR, Assoc. Prof.	Ankara University Medical Faculty, Department of Cardiovascular Surgery Ankara, Turkey, 06340
Study Chair:	ONDER ASLAN, Prof.	Ankara University Medical Faculty, Department of Hematology Ankara, Turkey

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Baran Ç, Durdu S, Dalva K, Zaim Ç, Dogan A, Ocakoglu G, Gürman G, Arslan Ö, Akar AR. Effects of preoperative short term use of atorvastatin on endothelial progenitor cells after coronary surgery: a randomized, controlled trial. Stem Cell Rev. 2012 Sep;8(3):963-71. doi: 10.1007/s12015-011-9321-z.

Responsible Party:	A. Ruchan Akar, Professor, Consultant Cardiovascular Surgeon, Ankara University
ClinicalTrials.gov Identifier:	NCT01096875 History of Changes
Other Study ID Numbers:	UMT0043
First Posted:	March 31, 2010
Results First Posted:	July 9, 2014
Last Update Posted:	July 9, 2014
Last Verified:	July 2014

Keywords provided by A. Ruchan Akar, Ankara University:

Endothelial progenitor cells; Atorvastatin; Coronary surgery

Additional relevant MeSH terms:

Atorvastatin Calcium; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites	Molecular Mechanisms of Pharmacological Action; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Enzyme Inhibitors