Perioperative Simvastatin Therapy in Major Colorectal Surgery: A Prospective, Double-Blind Randomized Controlled Trial

Abstract

Statins have numerous potential benefits relevant to abdominal surgery, and their use has been associated with a reduction in the systemic inflammatory response syndrome, wound infection, and anastomotic leak after colorectal surgery. However, this clinical evidence is limited to retrospective studies. The aim of this study was to prospectively investigate whether perioperative statin therapy can decrease the incidence of complications after major colorectal surgery. A prospective, double-blind, parallel-group, randomized controlled trial was conducted at 3 tertiary hospitals in New Zealand, between October 2011 and August 2013. Adult patients undergoing elective colorectal resection for any indication or reversal of Hartmann's procedure were randomized with a 1:1 patient allocation ratio to receive either 40 mg oral simvastatin or placebo once daily for 3 to 7 days preoperatively until 14 days postoperatively. The primary outcome was the overall incidence of complications for 30 days postoperatively. Secondary outcomes included the systemic and peritoneal cytokine response (interleukin [IL]-1α, IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]α) on postoperative day1. There were 132 patients included in the study (65 simvastatin, 67 placebo). There were no significant differences between the 2 groups at baseline with regard to patient, operation, and disease characteristics. There were no significant differences between the 2 groups in the incidence, grade, and type of postoperative complications (simvastatin: 44 [68%] vs placebo: 50 [75%], odds ratio 0.71 [95% CI 0.33 to 1.52], p= 0.444). Plasma concentrations of IL-6, IL-8, and TNFα, and peritoneal concentrations of IL-6 and IL-8, were significantly lower in the simvastatin group postoperatively. Perioperative simvastatin therapy in major colorectal surgery attenuates the early proinflammatory response to surgery, but there were no differences in postoperative complications.