The effect of oral simvastatin on fibrinolytic activity after colorectal surgery-a pilot study.
Studies conducted in animal models have shown that statins (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors) reduce adhesion formation by upregulating fibrinolysis. The aim of this study was to determine the effect of orally administered statins on the promoters and inhibitors of the fibrinolytic pathway.



In a previously described double-blinded clinical trial, 144 patients undergoing elective colorectal resection, or reversal of Hartmann's procedure were randomized to receive 40 mg once daily oral simvastatin 3-7 d before surgery or placebo. For the purposes of the present study, peritoneal drain fluid was collected postoperatively from patients to measure active tissue plasminogen activator (tPA), tissue plasminogen activator total antigen, active plasminogen activator inhibitor-1 (PAI-1), plasminogen activator inhibitor total antigen (PAI-1TA), plasminogen activator inhibitor-1 and tissue plasminogen activator complex (PAI-1/tPA). These were analyzed using ELISA. The number of hospitalizations and complications related to small bowel obstruction (SBO) were recorded at 2 y after surgery.



A total of 95 patients (72%) had sufficient peritoneal drain fluid suitable for ELISA analysis. Of them, 46 patients (48%) were from the oral simvastatin group. Mean tPA and tPA total antigen concentrations in peritoneal fluid were similar between the two groups. Mean PAI-1 and PAI-1 TA concentrations in the statin and placebo group were also similar. Mean PAI-1/tPA complex concentration was similar between the two groups. The number of hospitalizations from SBOs were 5 and 4 in the statin and placebo groups respectively (P = 0.46). The overall mortality at 2-year post-surgery was similar between the two groups (P = 0.59).



In this pilot study involving humans, oral simvastatin had no measured effect on the peritoneal fibrinolytic pathway in the first 24 h after colorectal surgery. Analysis of clinical outcomes also showed that oral simvastatin did not reduce hospitalizations for SBO in the 2 y after surgery. Further studies may be useful to evaluate whether fibrinolytic pathways beyond 24 h are altered after systemic administration of statins and to evaluate the use of higher doses of statins, perhaps used intraperitoneally rather than systemically.
Department of Surgery, South Auckland Clinical Campus, Middlemore Hospital, Auckland, New Zealand. Electronic address: zanazir@hotmail.com.
Zanazir E
ZE
Alexander
Department of Surgery, South Auckland Clinical Campus, Middlemore Hospital, Auckland, New Zealand.
Bruce
B
Su'a
Department of Surgery, South Auckland Clinical Campus, Middlemore Hospital, Auckland, New Zealand.
Caleb T G
CT
Hill
Department of Surgery, South Auckland Clinical Campus, Middlemore Hospital, Auckland, New Zealand.
Mataroria P
MP
Lyndon
Department of Surgery, South Auckland Clinical Campus, Middlemore Hospital, Auckland, New Zealand.
Primal P
PP
Singh
Department of Surgery, South Auckland Clinical Campus, Middlemore Hospital, Auckland, New Zealand.
Andrew G
AG
Hill
D015179:Colorectal Neoplasms / Q000601:surgery*; D013505:Digestive System Surgical Procedures / Q000009:adverse effects; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D019821:Simvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D000267:Tissue Adhesions / Q000209:etiology / Q000517:prevention & control*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin
Adhesion; Biomarker; Colorectal; Fibrinolysis; Simvastatin