title: NSAIDs, statins, low-dose aspirin and PPIs, and the risk of oesophageal adenocarcinoma among patients with Barrett's oesophagus: a population-based case-control study.
abstract: OBJECTIVE
  Non-steroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), low-dose aspirin and statins may decrease the risk of oesophageal adenocarcinoma (OAC) among patients with Barrett's oesophagus (BO). However, previous studies did not adequately address bias and confounding. Our objective was to estimate the risk of OAC among patients with BO exposed to NSAIDs, statins and PPIs.
  
  
  METHODS
  Case-control study nested within a BO cohort.
  
  
  METHODS
  Two primary care databases (the UK and the Netherlands (NL)).
  
  
  METHODS
  Cases were adults ≥18 years of age with OAC or high-grade dysplasia (HGD) diagnosis ≥1 year after BO diagnosis. Controls were matched on age, sex, year of BO diagnosis and database.
  
  
  METHODS
  Drug use was assessed from BO diagnosis until matching date.
  
  
  METHODS
  Adjusted ORs with 95% CI were calculated by conditional logistic regression.
  
  
  RESULTS
  Within the BO cohort (n=15 134), 45 OAC (UK: 40, NL: 5) and 12 HGD cases (NL: 12) were identified. ORa for OAC during NSAID use was 1.2 (95% CI 0.6 to 2.5) and during statin use for >3 years 0.5 (95% CI 0.1 to 1.7). When including HGD cases (n=57), ORa for NSAID use was 0.9 (95% CI 0.5 to 1.8) and for statin use >3 years 0.5 (95% CI 0.1 to 1.7). Higher doses of statins showed lower estimates for OAC and HGD, though not statistically significant. Low-dose aspirin and PPIs did not significantly decrease the risk of OAC and HGD.
  
  
  CONCLUSIONS
  In this population-based nested case-control study, use of NSAIDs, PPIs, low-dose aspirin or statins did not reduce the risk of HGD and OAC among patients with BO. These findings indicate that for an unselected group of patients with BO chemoprevention by use of drugs to reduce progression to HGD and OAC should not be directly considered as routine care.
authors: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Gwen M C
authors: GM
authors: Masclee
authors: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Preciosa M
authors: PM
authors: Coloma
authors: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Manon C W
authors: MC
authors: Spaander
authors: Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Ernst J
authors: EJ
authors: Kuipers
authors: Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors: Miriam C J M
authors: MC
authors: Sturkenboom
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001471:Barrett Esophagus / Q000188:drug therapy* / Q000453:epidemiology; D016022:Case-Control Studies; D004938:Esophageal Neoplasms / Q000453:epidemiology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012042:Registries; D012306:Risk; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D054328:Proton Pump Inhibitors; D001241:Aspirin
keywords: EPIDEMIOLOGY
references: Am J Epidemiol. 2008 Aug 1;168(3):237-49
references: 18550563
references: Lancet. 2011 Jan 1;377(9759):31-41
references: 21144578
references: Clin Gastroenterol Hepatol. 2010 Mar;8(3):235-44; quiz e32
references: 19850156
references: Gastroenterology. 2012 Mar;142(3):442-452.e5; quiz e22-3
references: 22108196
references: Cancer Epidemiol Biomarkers Prev. 2012 Mar;21(3):456-61
references: 22241250
references: Gastroenterology. 2012 May;142(5):e20-1; author reply e21
references: 22449575
references: Gut. 2012 Jul;61(7):970-6
references: 21997553
references: Eur J Gastroenterol Hepatol. 2012 Aug;24(8):917-23
references: 22569083
references: Gastroenterology. 2012 Oct;143(4):917-26.e1
references: 22796132
references: Clin Gastroenterol Hepatol. 2013 Feb;11(2):109-18; quiz e13-4
references: 22982096
references: Clin Gastroenterol Hepatol. 2013 Apr;11(4):382-8
references: 23200977
references: J Dig Dis. 2013 May;14(5):222-30
references: 23421723
references: Clin Gastroenterol Hepatol. 2013 Jun;11(6):620-9
references: 23357487
references: Epidemiology. 2011 Mar;22(2):228-31
references: 21228697
references: J Natl Cancer Inst. 2011 Jul 6;103(13):1049-57
references: 21680910
references: N Engl J Med. 2011 Oct 13;365(15):1375-83
references: 21995385
references: J Thorac Cardiovasc Surg. 2011 Nov;142(5):1152-60
references: 22014341
references: Gastroenterology. 2011 Dec;141(6):2000-8; quiz e13-4
references: 21878200
references: Gut. 2004 Aug;53(8):1070-4
references: 15247170
references: J Epidemiol Community Health. 2004 Aug;58(8):635-41
references: 15252064
references: Fam Pract. 1992 Sep;9(3):330-9
references: 1459391
references: Health Libr Rev. 1994 Sep;11(3):177-82
references: 10139676
references: Cancer Res. 1998 Jul 15;58(14):2929-34
references: 9679948
references: Am J Public Health. 2005;95 Suppl 1:S144-50
references: 16030331
references: Lancet Oncol. 2005 Dec;6(12):945-52
references: 16321762
references: Gut. 2006 Nov;55(11):1538-44
references: 16785284
references: Pharmacoepidemiol Drug Saf. 2007 Apr;16(4):393-401
references: 17066486
references: J Physiol Pharmacol. 2007 Aug;58 Suppl 3:141-8
references: 17901590
references: Aliment Pharmacol Ther. 2008 Feb 15;27(4):316-20
references: 18062791
references: Am J Epidemiol. 2008 Feb 15;167(4):492-9
references: 18056625
references: Gastrointest Endosc. 2008 Mar;67(3):394-8
references: 18045592
references: Am J Gastroenterol. 2008 Mar;103(3):788-97
references: 18341497
references: Am J Gastroenterol. 2008 Apr;103(4):825-37
references: 18371146
references: Methods Inf Med. 1999 Dec;38(4-5):339-44
references: 10805025
references: J Natl Cancer Inst. 2002 Mar 20;94(6):422-9
references: 11904314
references: Gastroenterology. 2003 Jan;124(1):47-56
references: 12512029
references: Gastroenterology. 2014 Mar;146(3):661-8
references: 24315828
references: Aliment Pharmacol Ther. 2014 May;39(9):984-91
references: 24617286
references: Br J Cancer. 2014 Apr 29;110(9):2378-88
references: 24651385
references: Aliment Pharmacol Ther. 2014 Jun;39(11):1321-30
references: 24738722
references: Gut. 2014 Aug;63(8):1229-37
references: 24221456
references: Gastroenterology. 2014 Aug;147(2):314-23
references: 24798416
references: N Engl J Med. 2014 Aug 28;371(9):836-45
references: 25162890
references: Gastroenterology. 2014 Oct;147(4):784-792.e9; quiz e13-4
references: 24937265
references: Gastroenterology. 2010 Jun;138(7):2260-6
references: 20188100
references: Gut. 2010 Aug;59(8):1030-6
references: 20639249
references: Br J Cancer. 2009 Feb 10;100(3):551-7
references: 19156150