NSAIDs: increase the risk of gastrointestinal bleeding, perforations and ulcers

Clinical bottom line (level 1a)

  1. Patients who take oral NSAIDs for more than 4 days are at increased risk of developing gastrointestinal complications including bleeding, ulcers and perforation.
Ofman et al: J Rheumatol 2002; 29 : 804-812
Expires June 2004

The study

Systematic review of all studies of
  • Patients: requiring NSAIDs
  • Intervention: on oral NSAIDs for > 4 days
  • Outcome: perforations, ulcers, bleeding

Articles found in all languages using Medline, Biosis, Embase, Healthstar, 1966 to 1998 (search terms: detailed in text ) and searching bibliographies of previous reviews and personal files. The FDA was contacted for unpublished data.

Selection criteria: by 2 independent reviewers - disagreement was resolved by consensus
Appraisal criteria: by 2 independent reviewers - disagreement was resolved by consensus. Controlled clinical trials assessed by Jadad criteria. Other trials were assessed based on comparability between groups, blinding and treatment of loss to follow-up.
Articles excluded if:
  • animal subjects
  • NSAID not given orally
  • patients aged < 18
  • review, editorial, letter, clinical practice guideline or consensus statement
  • no outcome of interest reported
  • only endoscopic findings reported

  • 16 RCTs involving 4431 patients comparing NSAIDs v. placebo
  • 9 cohort studies with over 750000 person-years exposure
  • 23 case-control studies involving 25732 patients

The evidence

Outcome Time to outcome CER OR
(95% CI)		 NN?
(% CI)
RCTs: perforations, ulcer, bleeding weeks /
(%)		 5.36
(1.79 to 16.1)
case-control studies: perforations, ulcers, bleeding weeks /
(%)		 3.0
(2.5 to 3.7)

  • Cohort studies: perforations, ulcers, bleeding: RR 2.7 (95% CI: 2.1 to 3.5)

Comments

  1. Twenty papers in mainly Eastern European languages were not translated.
  2. Few case-control studies had blinded outcome assessment.

Citation

  1. Ofman JJ, Maclean CH, Straus WL, et al: a metaanalysis of severe upper gastrointestinal complications of nonsteroidal antiinflammatory drugs. J Rheumatol 2002; 29 : 804-812
Search Terms: from ACP Journal Club other articles noted
Contributor: Chris Ball, June 2002
Reviewer:

Clinical Question.
Patient requiring NSAIDs
Intervention or Exposure on NSAIDs for > 4 days
Outcome gastrointestinal perforation, ulcers, bleeding