The gastrointestinal effects of nonselective NSAIDs and COX-2-selective inhibitors

Semin Arthritis Rheum. 2002 Dec;32(3 Suppl 1):25-32. doi: 10.1053/sarh.2002.37217.


Nonsteroidal anti-inflammatory drugs (NSAIDs), which include aspirin, are among the most frequently prescribed medications worldwide. The main factor limiting use of NSAIDs is concern about their gastrointestinal (GI) side effects. The purpose of this article is to review the incidence, pathophysiology, and risk factors of GI side effects associated with NSAID therapy. Upper GI symptoms, such as dyspepsia, occur in 15% to 60% of NSAID users, twice as often as in individuals not taking NSAIDs. The prevalence of gastric or duodenal ulcers in patients taking NSAIDs regularly is approximately 15% to 30%. The annual incidence of NSAID-related clinical upper GI events (complicated and symptomatic ulcers) is approximately 2.5% to 4.5%, with the annual incidence of serious complications (severe bleeding, perforation, and obstruction) about 1% to 1.5%. A history of ulcer or GI complications, advanced age, concomitant anticoagulation therapy or corticosteroid use, and high-dose or multiple NSAID therapy are associated with an increased risk of GI events during NSAID therapy. The cyclooxygenase (COX)-2 specific inhibitors (coxibs) have been developed in order to improve the GI safety and tolerability profile of therapy with NSAIDs. In numerous clinical trials, coxibs have been shown to have efficacy similar to that of nonselective NSAIDs, but are associated with significantly fewer endoscopic ulcers. In addition, 2 large outcome trials indicated that coxibs can also reduce the incidence of clinically important GI events.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors / adverse effects*
  • Duodenal Ulcer / chemically induced*
  • Duodenal Ulcer / epidemiology
  • Duodenal Ulcer / physiopathology
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / pathology
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Isoenzymes / antagonists & inhibitors*
  • Membrane Proteins
  • Middle Aged
  • Prevalence
  • Prostaglandin-Endoperoxide Synthases
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Stomach Ulcer / chemically induced*
  • Stomach Ulcer / epidemiology
  • Stomach Ulcer / physiopathology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Isoenzymes
  • Membrane Proteins
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases