Original Article—Alimentary Tract

Journal of Gastroenterology

, Volume 48, Issue 7, pp 830-838

First online:

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

  • Saharat JarupongprapaAffiliated withDepartment of Medicine, Nakornprathom Hospital
  • , Prapassorn UssavasodhiAffiliated withDivision of Rheumatology, Department of Medicine Siriraj Hospital, Mahidol University
  • , Wanruchada KatchamartAffiliated withDivision of Rheumatology, Department of Medicine Siriraj Hospital, Mahidol University Email author 

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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).


To compare the adverse GI effects between COX-2 inhibitors and NSAIDs plus PPI.


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.


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).


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.


Cyclooxygenase-2 inhibitors Non-selective Non-steroidal anti-inflammatory drugs Proton-pump inhibitors Gastrointestinal toxicity Meta-analysis