Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs

Aliment Pharmacol Ther. 2006 Sep 1;24(5):751-67. doi: 10.1111/j.1365-2036.2006.03043.x.


Background: Lower gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs) are much more poorly characterized than upper gastrointestinal effects.

Aim: To determine if NSAIDs increase lower gastrointestinal adverse effects and if the risk with non-selective NSAIDs is greater than with cyclooxygenase-2-selective inhibitors (coxibs).

Methods: Computerized databases were searched to identify studies of NSAID use reporting on lower gastrointestinal integrity (e.g. permeability), visualization (e.g. erosions, ulcers) and clinical events.

Results: Designs in 47 studies were randomized (18), case-control (14), cohort (eight) and before-after (seven). Non-selective-NSAIDs had significantly more adverse effects vs. no NSAIDs in 20 of 22 lower gastrointestinal integrity studies, five of seven visualization studies, seven of 11 bleeding studies (OR: 1.9-18.4 in case-control studies), two of two perforation studies (OR: 2.5-8.1) and five of seven diverticular disease studies (OR: 1.5-11.2). Coxibs had significantly less effect vs. non-selective-NSAIDs in three of four integrity studies, one endoscopic study (RR mucosal breaks: 0.3), and two randomized studies (RR lower gastrointestinal clinical events: 0.5; haematochezia: 0.4).

Conclusions: An increase in lower gastrointestinal injury and clinical events with non-selective-NSAIDs appears relatively consistent across the heterogeneous collection of trials. Coxibs are associated with lower rates of lower gastrointestinal injury than non-selective-NSAIDs. More high-quality trials are warranted to more precisely estimate the effects of non-selective-NSAIDs and coxibs on the lower gastrointestinal tract.

Publication types

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

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Cyclooxygenase 2 Inhibitors / adverse effects
  • Diverticulum / chemically induced
  • Gastrointestinal Hemorrhage / chemically induced
  • Humans
  • Inflammation / chemically induced
  • Intestinal Diseases / chemically induced*
  • Intestine, Large / drug effects
  • Intestine, Large / physiopathology
  • Intestine, Small / drug effects
  • Intestine, Small / physiopathology
  • Lower Gastrointestinal Tract
  • Permeability / drug effects


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