title: Influence of Statins and Cholesterol on Mortality Among Patients With Pancreatic Cancer.
abstract: Recent studies have suggested associations between statins and enhanced survival among patients with pancreatic ductal adenocarcinoma (PDAC). However, the relationship between statins, cholesterol, and survival remains unclear.
  
  
  
  We conducted a retrospective cohort study on 2142 PDAC patients in a regional integrated healthcare system from 2006 to 2014. Electronic pharmacy records were used to abstract information on the type, length, and dosage of statin exposures starting in the year prior to diagnosis. The cumulative and individual effects of simvastatin, lovastatin, atorvastatin, pravastatin, and rosuvastatin on mortality were assessed using Cox proportional hazards regression. Statins were evaluated as any use (pre- and postdiagnosis as a time-dependent variable) and baseline use (prediagnosis only). We also evaluated whether low-density lipoprotein (LDL) cholesterol, measured at various time windows prior to diagnosis, had an independent influence on survival. Additional analyses were performed to examine whether cholesterol mediated the relationship between statins and mortality. All models included age, race, stage, surgery, gemcitabine-based chemotherapy, and the Charlson comorbidity index as covariates.
  
  
  
  Any (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.79 to 0.97) and baseline (HR = 0.88, 95% CI = 0.79 to 0.98) statin use were both associated with a decreased risk in mortality. When assessing individual statins, we found reduced mortality among simvastatin (HR = 0.87, 95% CI = 0.77 to 0.98) and atorvastatin (HR = 0.58, 95% CI = 0.46 to 0.72) users. Cholesterol was not associated with mortality and did not mediate any relationships between statins and survival.
  
  
  
  Statin use rather than cholesterol level was associated with lower mortality risk in patients with pancreatic cancer. Statins appear to improve survival through a lipid-independent mechanism.
authors.affiliation: Affiliations of authors: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA (BZH, AHX); Department of Internal Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (JIC), and Division of Gastroenterology, Center for Pancreatic Care, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (BUW), Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA (BZH); David Geffen School of Medicine at UCLA, Los Angeles, CA (EL).
authors.forename: Brian Z
authors.initials: BZ
authors.lastname: Huang
authors.affiliation: Affiliations of authors: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA (BZH, AHX); Department of Internal Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (JIC), and Division of Gastroenterology, Center for Pancreatic Care, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (BUW), Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA (BZH); David Geffen School of Medicine at UCLA, Los Angeles, CA (EL).
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Chang
authors.affiliation: Affiliations of authors: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA (BZH, AHX); Department of Internal Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (JIC), and Division of Gastroenterology, Center for Pancreatic Care, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (BUW), Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA (BZH); David Geffen School of Medicine at UCLA, Los Angeles, CA (EL).
authors.forename: Erica
authors.initials: E
authors.lastname: Li
authors.affiliation: Affiliations of authors: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA (BZH, AHX); Department of Internal Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (JIC), and Division of Gastroenterology, Center for Pancreatic Care, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (BUW), Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA (BZH); David Geffen School of Medicine at UCLA, Los Angeles, CA (EL).
authors.forename: Anny H
authors.initials: AH
authors.lastname: Xiang
authors.affiliation: Affiliations of authors: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA (BZH, AHX); Department of Internal Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (JIC), and Division of Gastroenterology, Center for Pancreatic Care, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (BUW), Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA (BZH); David Geffen School of Medicine at UCLA, Los Angeles, CA (EL).
authors.forename: Bechien U
authors.initials: BU
authors.lastname: Wu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069059:Atorvastatin / Q000627:therapeutic use; D002140:California / Q000453:epidemiology; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality* / Q000556:secondary / Q000628:therapy; D008078:Cholesterol, LDL / Q000097:blood*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D011307:Drug Prescriptions; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008148:Lovastatin / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D017035:Pravastatin / Q000627:therapeutic use; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use; D019821:Simvastatin / Q000627:therapeutic use; D015996:Survival Rate; D000093542:Gemcitabine
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D003841:Deoxycytidine; D000068718:Rosuvastatin Calcium; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin; D000093542:Gemcitabine