title: Impact of statin use on survival in patients undergoing resection for early-stage pancreatic cancer.
abstract: OBJECTIVE
  It has been suggested that statins exert potential anti-tumor effects. The relationship between statin use and outcomes in pancreatic cancer is controversial. We hypothesized that statin use at baseline would impact survival among patients with early-stage pancreatic cancer and that the effect might vary by individual statin agent.
  
  
  METHODS
  We conducted a retrospective cohort study on data from an integrated healthcare system. We included patients with pancreatic cancer stage I-IIb who underwent resection for curative intent between January 2005 and January 2011. Baseline statin use was characterized as any prior use as well as active use of either simvastatin or lovastatin. Intensity of exposure was calculated as average daily dose prior to surgery. Overall and disease-free survival was assessed from surgery until the end of study (April 2014). We used the Kaplan-Meier method and Cox proportional hazards regression to evaluate the impact of baseline statin use on survival, adjusting for age, sex, Charlson comorbidity score, resection margin, disease stage, and receipt of adjuvant chemotherapy.
  
  
  RESULTS
  Among 226 patients, 71 (31.4%) had prior simvastatin use and 27 (11.9%) had prior lovastatin use at baseline. Prior simvastatin but not lovastatin use was associated with improved survival (median 28.5 months (95% confidence limit (CL) 20.8, 38.4) for simvastatin vs. 12.9 months (9.6, 15.5) for lovastatin vs. 16.5 months (14.1, 18.9) for non-statin users; log-rank P=0.0035). In Cox regression, active simvastatin use was independently associated with reduced risk for mortality (adjusted hazard ratio (HR) 0.56 (95% CL 0.38, 0.83), P=0.004) and risk for recurrence (adjusted HR 0.61 (0.41, 0.89), P=0.01). Survival improved significantly among patients who received moderate-high-intensity (median 42.1 months (24.0,52.7)) doses compared with those who received low-intensity doses of simvastatin (median 14.1 months (8.6, 23.8), log-rank P=0.03).
  
  
  CONCLUSIONS
  The effects of statins varied by agent and dose. Active use of moderate-high-dose simvastatin at baseline was associated with improved overall and disease-free survival among patients undergoing resection for pancreatic cancer.
authors.affiliation: Division of Gastroenterology, Center for Pancreatic Care, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA.
authors.forename: Bechien U
authors.initials: BU
authors.lastname: Wu
authors.affiliation: Department of Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Chang
authors.affiliation: Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Christie Y
authors.initials: CY
authors.lastname: Jeon
authors.affiliation: Program in Basic and Translational Pancreatic Research, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Pandol
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, California, USA.
authors.forename: Eunis W
authors.initials: EW
authors.lastname: Ngor
authors.affiliation: Department of Hepatobiliary and Oncologic Surgery, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Difronzo
authors.affiliation: Department of Pediatric Hematology and Oncology, Kaiser Permanente Los Angeles Medical Center, Los Angeles, California, USA.
authors.forename: Robert M
authors.initials: RM
authors.lastname: Cooper
mesh_terms: D000368:Aged; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D053208:Kaplan-Meier Estimate; D008148:Lovastatin / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D019821:Simvastatin / Q000008:administration & dosage*; D015996:Survival Rate
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D019821:Simvastatin