Clinical trial NCT01096875: Effects of Atorvastatin on Endothelial Progenitor Cells After Coronary Surgery
Official title: Assessment of the Effects of Atorvastatin on Endothelial Progenitor Cells After Coronary ByPass Surgery; A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Artery Bypass Surgery
Elective Surgical Procedure
Keywords: Endothelial progenitor cells
Atorvastatin
Coronary surgery
Lead sponsor: Ankara University
Sponsor class: OTHER
Collaborators: name: Turkish Society of Hematology
First posted: 2010-03-31
Enrollment: 60
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Endothelial Progenitor Cells (EPCs) Count (Cells/µl)
timeFrame: Postoperative 6th hours
Secondary outcomes:
measure: Left Ventricular Ejection Fraction (LVEF %) Measured at 30 Days Postoperatively
timeFrame: Change between statin and placebo groups at 30 days postoperatively
measure: High Sensitive C-reactive Protein (hsCRP mg/L)
timeFrame: Postoperative 6th hours
measure: High Sensitive C-reactive Protein (hsCRP mg/L)
timeFrame: 5 days postoperatively
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty, Department of Cardiovascular Surgery
state: Cebeci
Study officials:
affiliation: Ankara University Medical Faculty, Department of Cardiovascular Surgery Ankara, Turkey, 06340
name: RUCHAN AKAR, Assoc. Prof.
role: STUDY_DIRECTOR
affiliation: Ankara University Medical Faculty, Department of Hematology Ankara, Turkey
name: ONDER ASLAN, Prof.
role: STUDY_CHAIR
References:
citation: Baran C, Durdu S, Dalva K, Zaim C, Dogan A, Ocakoglu G, Gurman G, Arslan O, Akar AR. Effects of preoperative short term use of atorvastatin on endothelial progenitor cells after coronary surgery: a randomized, controlled trial. Stem Cell Rev Rep. 2012 Sep;8(3):963-71. doi: 10.1007/s12015-011-9321-z.