title: Simvastatin is associated with reduced risk of acute pancreatitis: findings from a regional integrated healthcare system.
abstract: OBJECTIVE
  To characterise the relationship between simvastatin and risk of acute pancreatitis (AP).
  
  
  METHODS
  We conducted a retrospective cohort study (2006-2012) on data from an integrated healthcare system in southern California. Exposure to simvastatin was calculated from time of initial dispensation until 60 days following prescription termination. AP cases were defined by ICD-9 CM 577.0 and serum lipase≥3 times normal. Patients were censored at death, last follow-up, and onset of AP or end-of-study. Incidence rate of pancreatitis among simvastatin users was compared with the adult reference population. Robust Poisson regression was used to generate risk ratio (RR) estimates for simvastatin use adjusted for age, gender, race/ethnicity, gallstone-related disorders, hypertriglyceridaemia, smoking and alcohol dependence. Analysis was repeated for atorvastatin.
  
  
  RESULTS
  Among 3,967,859 adult patients (median duration of follow-up of 3.4 years), 6399 developed an initial episode of AP. A total of 707,236 patients received simvastatin during the study period. Patients that received simvastatin were more likely to have gallstone-related disorders, alcohol dependence or hypertriglyceridaemia compared with the reference population. Nevertheless, risk of AP was significantly reduced with simvastatin use, crude incidence rate ratio 0.626 (95% CL 0.588, 0.668), p<0.0001. In multivariate analysis, simvastatin was independently associated with reduced risk of pancreatitis, adjusted RR 0.29 (95% CL 0.27, 0.31) after adjusting for age, gender, race/ethnicity, gallstone disorders, alcohol dependence, smoking and hypertriglyceridaemia. Similar results were noted with atorvastatin, adjusted RR 0.33(0.29, 0.38).
  
  
  CONCLUSIONS
  Use of simvastatin was independently associated with reduced risk of AP in this integrated healthcare setting. Similar findings for atorvastatin suggest a possible class effect.
authors.affiliation: Southern California Permanente Medical Group, 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: 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: In-Lu Amy
authors.initials: IL
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D019033:Delivery of Health Care, Integrated; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000139:chemically induced* / Q000453:epidemiology*; D012189:Retrospective Studies; D018570:Risk Assessment; D019821:Simvastatin / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019821:Simvastatin
keywords: Pancreas; Pancreatic Disease; Pancreatic Disorders; Pancreatic Epidemiology; Pancreatitis
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