title: Risks of clinically significant upper gastrointestinal events with etodolac and naproxen: a historical cohort analysis.
abstract: OBJECTIVE
  Etodolac is a generic nonsteroidal anti-inflammatory drug (NSAID). Previous in vitro studies have shown that etodolac is a selective inhibitor of cyclooxygenase (COX)-2 with selectivity in between that of other COX-2 inhibitors such as celecoxib and rofecoxib. However, there are no outcomes data assessing clinically significant upper gastrointestinal (CSUGI) events with etodolac.
  
  
  METHODS
  A historical cohort study was performed at the Dallas Veterans Affairs Medical Center in which 16,286 veteran patients (5596 patient-years) received etodolac or naproxen during a 3-year period without concurrent use of other ulcerogenic drugs other than low-dose aspirin. The primary outcome was the CSUGI event rate of the etodolac and naproxen groups without concomitant low-dose aspirin.
  
  
  RESULTS
  The incidence of CSUGI events was .78% and .24% for naproxen and etodolac, respectively. In the NSAID-naive subset, the incidence of CSUGI events was .99% and .24% for naproxen and etodolac, respectively. Compared with naproxen, etodolac was associated with a reduction in upper gastrointestinal events, corresponding to an odds ratio of .39 (95% confidence interval, .20-.76; P = .006). Concomitantly used low-dose aspirin increased event rates with naproxen 2-fold and etodolac 9-fold. Hence, there was no significant difference in gastrointestinal event rates between etodolac and naproxen when low-dose aspirin was taken concomitantly.
  
  
  CONCLUSIONS
  Etodolac is a generic COX-2 selective inhibitor that reduces CSUGI events compared with the nonselective NSAID naproxen. However, concomitant use of low-dose aspirin negates the gastrointestinal safety advantages of etodolac.
authors.affiliation: Department of Pharmacy, Dallas Veterans Affairs Medical Center, Dallas, TX 75216, USA.
authors.forename: Rick A
authors.initials: RA
authors.lastname: Weideman
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kelly
authors.forename: Salahuddin
authors.initials: S
authors.lastname: Kazi
authors.forename: Anh
authors.initials: A
authors.lastname: Cung
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Roberts
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Smith
authors.forename: George A
authors.initials: GA
authors.lastname: Sarosi
authors.forename: Bertis B
authors.initials: BB
authors.lastname: Little
authors.forename: Byron
authors.initials: B
authors.lastname: Cryer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D015331:Cohort Studies; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D017308:Etodolac / Q000627:therapeutic use*; D005260:Female; D005767:Gastrointestinal Diseases / Q000145:classification / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009288:Naproxen / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D017308:Etodolac; D009288:Naproxen; D001241:Aspirin