title: Comparison of gastrointestinal adverse effects between cyclooxygenase-2 inhibitors and non-selective, non-steroidal anti-inflammatory drugs plus proton pump inhibitors: a systematic review and meta-analysis.
abstract: BACKGROUND
  There are conflicting and inconsistent data regarding the gastrointestinal (GI) protective effect of cyclooxygenase-2 (COX-2) inhibitors and of non-steroidal anti-inflammatory drugs (NSAIDs) plus proton-pump inhibitors (PPI).
  
  
  OBJECTIVE
  To compare the adverse GI effects between COX-2 inhibitors and NSAIDs plus PPI.
  
  
  METHODS
  We performed a systematic review of randomized trials comparing GI adverse effects between COX-2 inhibitors and NSAID plus PPI. Trials were identified in MEDLINE, EMBASE, and the Cochrane Library. Primary outcomes were major GI complications including hemorrhage, perforation, and obstruction.
  
  
  RESULTS
  A total of nine trials involving 7,616 participants from 2002 to 2011 were included. All trials were randomized, double blinded, and placebo-controlled with moderate to high quality. COX-2 inhibitors were found to have significantly reduced the risk of major GI events, including perforation, obstruction, and bleeding (relative risk or RR 0.38, 95 % confidence interval or CI 0.25-0.56, p < 0.001); however, the benefit was significant only for patients who were at high risk for NSAID-related GI complications and long-term users. Additionally, the risk of diarrhea (RR 0.56, 95 % CI 0.35-0.9, p 0.02) and withdrawal (RR 0.77, 95 % CI 0.62-0.94, p 0.01) was significantly lower in use of COX-2 inhibitors, while the rate of dyspepsia was higher (RR 1.58, 95 % CI 1.26-1.98, p < 0.001).
  
  
  CONCLUSIONS
  COX-2 inhibitors significantly reduced the risk of perforation, obstruction, bleeding, diarrhea, and withdrawal due to GI adverse events, while the risk of dyspepsia was lower with NSAIDs plus PPI.
authors.affiliation: Department of Medicine, Nakornprathom Hospital, Nakornprathom, Thailand.
authors.forename: Saharat
authors.initials: S
authors.lastname: Jarupongprapa
authors.forename: Prapassorn
authors.initials: P
authors.lastname: Ussavasodhi
authors.forename: Wanruchada
authors.initials: W
authors.lastname: Katchamart
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012306:Risk
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D054328:Proton Pump Inhibitors