Long-term effects of nonsteroidal anti-inflammatory drugs and cyclooxygenase-2 selective agents on the small bowel: a cross-sectional capsule enteroscopy study

Clin Gastroenterol Hepatol. 2007 Sep;5(9):1040-5. doi: 10.1016/j.cgh.2007.04.031. Epub 2007 Jul 10.


Background & aims: Nonsteroidal anti-inflammatory drug (NSAID) gastropathy is sufficiently important as to warrant co-administration of misoprostol or proton pump inhibitors or a switch to selective cyclooxygenase (COX)-2 inhibitors. However, the serious ulcer outcome studies suggested that 40% of the clinically significant gastrointestinal bleeding originated more distally, presumably from NSAID enteropathy. We used capsule enteroscopy to study small-bowel damage in patients on long-term NSAIDs and COX-2-selective agents.

Methods: Sixty healthy volunteers acted as controls. One hundred twenty and 40 patients on long-term NSAIDs and COX-2 selective agents, respectively, underwent a capsule enteroscopy study. Small-bowel damage was categorized and quantitated.

Results: Sixty-two percent of patients on conventional NSAIDs were abnormal, which differed significantly (P < .001) from controls. The main pathology related to reddened folds (13%), denuded areas (39%), and mucosal breaks (29%). Two percent had diaphragm-like strictures and 3% had bleeding without an identifiable lesion. The damage, seen in 50% of patients on selective COX-2 inhibitors (reddened folds, 8%; denuded areas, 18%; and mucosal breaks, 22%), did not differ significantly (P > .5) from that seen with NSAIDs.

Conclusions: Long-term NSAIDs and COX-2-selective agents cause comparable small-bowel damage. This suggests an important role for COX-2 in the maintenance of small-bowel integrity. The results have implications for strategies that aim to minimize the gastrointestinal damage in patients requiring anti-inflammatory analgesics.

Publication types

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

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Capsule Endoscopy / methods*
  • Confidence Intervals
  • Cross-Sectional Studies
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • England / epidemiology
  • Female
  • Follow-Up Studies
  • Humans
  • Iceland / epidemiology
  • Intestinal Diseases / chemically induced
  • Intestinal Diseases / pathology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Intestine, Small / drug effects*
  • Intestine, Small / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Risk Factors
  • Time Factors


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors