title: The use of drugs acting on the renin-angiotensin system and the incidence of pancreatic cancer.
abstract: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensives. Recently, these drugs have been associated with a protective effect against pancreatic cancer, but data on this putative association remain limited. Thus, the objective of this study was to determine whether the use of ACEIs and/or ARBs is associated with a decreased risk of pancreatic cancer.
  
  
  
  We conducted a population-based cohort study, using a nested case-control analysis within the UK Clinical Practice Research Datalink population. The cohort consisted of all patients newly treated with antihypertensive drugs between 1 January 1995 and 31 December 2009, with follow-up until 31 December 2010. Cases were patients with newly diagnosed pancreatic cancer, which were matched with up to 10 controls on age, sex, calendar year of cohort entry, and duration of follow-up. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of pancreatic cancer incidence associated with ever use of ACEIs and ARBs. A secondary analysis was conducted to assess whether the incidence of pancreatic cancer varied with cumulative duration of use of these drugs.
  
  
  
  A cohort of 547 566 was assembled. During 3 040 332 person-years of follow-up, a total of 866 patients were newly diagnosed with pancreatic cancer (rate: 3/10 000 per year) and matched to 8636 controls. Overall, when compared with other antihypertensive drugs, the use of ACEIs was not associated with a decreased risk of pancreatic cancer overall (OR: 1.01, 95% CI: 0.86-1.17) or according to cumulative duration of use. The use of ARBs was not associated with a decreased risk of pancreatic cancer overall (OR: 0.93, 95% CI: 0.75-1.15), whereas a cumulative duration of use of 1-3 years was associated with a 38% decrease (OR: 0.62, 95% CI: 0.41-0.94), which returned to the null after >3 years of use (OR: 1.04, 95% CI: 0.74-1.46).
  
  
  
  The use of ARBs and ACEIs was not associated with an overall decreased risk of pancreatic cancer when compared with patients using other antihypertensive drugs. Additional research is needed to determine whether ARBs may confer a short-term protective effect.
authors.affiliation: Department of Oncology, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Victoria
authors.initials: V
authors.lastname: Mandilaras
authors.affiliation: Department of Oncology, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Bouganim
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.
authors.forename: Hui
authors.initials: H
authors.lastname: Yin
authors.affiliation: Department of Oncology, McGill University Health Centre, Montreal, QC, Canada.
authors.forename: Jamil
authors.initials: J
authors.lastname: Asselah
authors.affiliation: Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada.|Gerald Bronfman Department of Oncology, McGill University Health Centre, Montreal, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Azoulay
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D016022:Case-Control Studies; D004232:Diuretics / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000453:epidemiology*; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012189:Retrospective Studies; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics