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COX-1 Vs COX-2 inhibitors (relative risk of GI side effects)

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

Authoring team

  • there is evidence that the use of COX-2 inhibitors leads to a reduced incidence of dyspepsia by 2% to 3% (1)

  • the frequency of potentially serious gastrointestinal complications (e.g. bleeding or perforation) is approximately 1% with conventional NSAID treatment - the use of COX-2 inhibitors seems to lower this risk by 0.5.% to 1% (1)
    • this evidence means that 100 to 200 "typical" patients need to be treated (NNT) with a COX-2 inhibitor rather than a conventional NSAID to prevent one serious gastro-intestinal complication. In patients at low risk of gastrointestinal complications, the NNT to prevent a serious complication may be about 500 (2)

  • a MeReC review stated that (3)
    • cox-2 inhibitors, as a class, are associated with a lower GI risk than traditional NSAIDs. However, their GI-safety advantage is diminished when co-administered with aspirin
    • of the traditional NSAIDS, low-dose ibuprofen is associated with a lower GI risk than diclofenac and naproxen
    • use of a proton pump inhibitor (PPI) with any NSAID significantly reduces the risk of GI side effects
    • benefits from gastroprotection largely depend on the baseline risk that the individual has for GI complications. There is, as yet, very little direct evidence that adding a PPI to a cox-2 inhibitor is more beneficial than adding a PPI to a traditional NSAID


  • (1) Henry D, McGettigan P.Commentary on "Rofecoxib caused fewer endoscopic gastroduodenal ulcers than ibuprofen in osteoarthritis". Evidence Based Medicine 2000 May-June, 5 (3), 74. Comment on: Laine L, Harper S, Simon T et al, for the Rofecoxib Osteoarthritis Endoscopy Study Group. A randomized trial comparing the effect of rofecoxib, a cyclo-oxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis. Gastroenterology 1999; 117: 776-83.
  • (2) Emery P, Seidler H, Kvien TK et al. Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison. Lancet 1999;354; 2106-11.
  • (3) MeReC Extra 2007;30.

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