title: Gastrointestinal toxicity among patients taking selective COX-2 inhibitors or conventional NSAIDs, alone or combined with proton pump inhibitors: a case-control study.
abstract: OBJECTIVE
  To assess the risk of gastrointestinal perforation, ulcers, or bleeding (PUB) associated with the use of conventional nonsteroidal anti-inflammatory drugs (NSAIDs) with proton pump inhibitors (PPIs) and selective COX-2 inhibitors, with or without PPIs compared with conventional NSAIDs.
  
  
  METHODS
  A case-control study was performed within conventional NSAIDs and/or selective COX-2 inhibitors users identified from the Dutch PHARMO Record Linkage System in the period 1998-2012. Cases were patients aged ≥18 years with a first hospital admission for PUB. For each case, up to four controls were matched for age and sex at the date a case was hospitalized (index date). Logistic regression analysis was used to calculate odds ratios (ORs).
  
  
  RESULTS
  At the index date, 2634 cases and 5074 controls were current users of conventional NSAIDs or selective COX-2 inhibitors. Compared with conventional NSAIDs, selective COX-2 inhibitors with PPIs had the lowest risk of PUB (adjusted OR 0.51, 95% confidence interval [CI]: 0.35-0.73) followed by selective COX-2 inhibitors (adjusted OR 0.66, 95%CI: 0.48-0.89) and conventional NSAIDs with PPIs (adjusted OR 0.79, 95%CI: 0.68-0.92). Compared with conventional NSAIDs, the risk of PUB was lower for those aged ≥75 years taking conventional NSAIDs with PPIs compared with younger patients (adjusted interaction OR 0.79, 95%CI: 0.64-0.99). However, those aged ≥75 years taking selective COX-2 inhibitors, the risk was higher compared with younger patients (adjusted interaction OR 1.22, 95%CI: 1.01-1.47).
  
  
  CONCLUSIONS
  Selective COX-2 inhibitors with PPIs, selective COX-2 inhibitors, and conventional NSAIDs with PPIs were associated with lower risks of PUB compared with conventional NSAIDs. These effects were modified by age. © 2017 The Authors. Pharmacoepidemiology & Drug Safety Published by John Wiley & Sons Ltd.
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, The Netherlands.|Department of Pharmacology, Medical Faculty, Lambung Mangkurat University, Banjarmasin, Indonesia.
authors.forename: Mohammad
authors.identifier: http://orcid.org/0000-0003-2299-5080
authors.initials: M
authors.lastname: Bakhriansyah
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, The Netherlands.
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Souverein
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, The Netherlands.
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.affiliation: Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, The Netherlands.
authors.forename: Olaf H
authors.initials: OH
authors.lastname: Klungel
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D016022:Case-Control Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D005260:Female; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced / Q000453:epidemiology* / Q000517:prevention & control; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010146:Pain / Q000188:drug therapy*; D059408:Pain Management / Q000009:adverse effects* / Q000379:methods; D010437:Peptic Ulcer / Q000139:chemically induced / Q000150:complications / Q000453:epidemiology* / Q000517:prevention & control; D010439:Peptic Ulcer Perforation / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D054328:Proton Pump Inhibitors / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D054328:Proton Pump Inhibitors
keywords: bleeding; conventional NSAIDs; gastrointestinal toxicity; perforation; proton pump inhibitors; selective COX-2 inhibitors; ulcers