Effects of Preoperative Short Term Use of Atorvastatin on Endothelial Progenitor Cells after Coronary Surgery: A Randomized, Controlled Trial

Abstract

We investigated the effects of short-term use of atorvastatin on CD34+/VEGF-R2+/CD133+/CD45- endothelial progenitor cell (EPC) count after on-pump coronary artery bypass surgery (CABG). Between Feb-2010 and May-2010, we randomly assigned, in a placebo-controlled, double-blind study, 60 consecutive patients who underwent isolated, first-time CABG to receive either 14-day atorvastatin (40 mg/day) or placebo preoperatively. Urgent CABG and recent myocardial infarction were excluded. EPCs were quantified (cells/μl) by flow cytometric phenotyping obtained from venous blood samples collected preoperatively (T(1)), 6-hours (T(2)), and on the 5th day postoperatively (T(3)). Levels of markers of inflammation and serum cardiac troponin I were also measured preoperatively and daily until day-5 after surgery. There were no differences in baseline risk factors including cholesterol profiles, and EuroSCORES between the groups. The composite primary end-point, favored statin group with higher amount of circulating, early EPC count (cells/μl) at all time points compared with placebo (T(1), 2.30±0.02 versus 1.58±0.03, p<0.001; T(2), 5.00±0.06 versus 2.19±0.06, p<0.001; T(3), 3.03±0.08 versus 1.78±0.02, p<0.001). Postoperative hsCRP rise were inversely correlated with EPC count, and were significantly lower in the statin group (T(1), 0.8 ± 0.1 versus 2.2±1.5, p<0.001; T(2), 72.9±3.2 versus 96.0±3.6, p<0.001; T(3), 4.3±1.2 versus 11.4±4.1, p<0.001). Furthermore, the incidence of postoperative atrial fibrillation was significantly lower in the statin group compared to placebo (3.3% versus 23%, p=0.02). Short-term atorvastatin use increases circulating early EPCs both pre- and post-operatively and is associated with better preservation of sinus rhythm and reduced hsCRP levels. (ClinicalTrials.gov number, NCT01096875).