Paper

Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis

BMJ 1996; 312 doi: 10.1136/bmj.312.7046.1563 (Published 22 June 1996)
Cite this as: BMJ 1996;312:1563
  1. David Henry, senior lecturer in clinical pharmacologyal,
  2. Lynette L-Y Lim, senior lecturer in biostatisticsa,
  3. Luis A Garcia Rodriguez, directorb,
  4. Susanne Perez Gutthann, head of pharmacoepidemiology researchc,
  5. Jeffrey L Carson, professor and chiefd,
  6. Marie Griffin, associate professor in medicine and preventive medicinee,
  7. Ruth Savage, general practitionerf,
  8. Richard Logan, reader in clinical epidemiologyg,
  9. Yola Moride, assistant professorh,
  10. Chris Hawkey, professor of gastroenterologyi,
  11. Suzanne Hill, acting head, drug safety, evaluation boardj,
  12. James T Fries, professor of medicine
  1. a Centre for Clinical Epidemiology and Biostatistics, Faculty of Medicine and Health Sciences, University of Newcastle, New South Wales, Australia
  2. b Centro Espanol de Investigacion, Farmacoepidemiologica, Universidad Complutense de Madrid, 28040 Madrid, Spain
  3. c Pharmacoepidemiology Research, Ciba-Geigy SA, Medical Department, 08013 Barcelona, Spain
  4. d Division of General Internal Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA
  5. e Department of Preventive Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
  6. f Department of Rheumatology, Christchurch Hospital, Christchurch, New Zealand
  7. g Department of Public Health and Epidemiology, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH
  8. h Centre for Clinical Epidemiology and Community Studies, McGill University-Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada
  9. i Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH
  10. j Therapeutics Goods Administration, Department of Human Services and Health, PO Box 100, Woden, ACT 2606, Australia
  11. k Stanford University School of Medicine, Suite 203, Palo Alto, CA 94304-1808, USA
  • Accepted 12 April 1996

Abstract

Objective: To compare the relative risks of serious gastrointestinal complications reported with individual non-steroidal anti-inflammatory drugs.

Design: Systematic review of controlled epidemiological studies that found a relation between use of the drugs and admission to hospital for haemorrhage or perforation.

Setting: Hospital and community based casecontrol and cohort studies.

Main outcome measures: (a) Estimated relative risks of gastrointestinal complications with use of individual drugs, exposure to ibuprofen being used as reference; (b) a ranking that best summarised the sequence of relative risks observed in the studies.

Results: 12 studies met the inclusion criteria. 11 provided comparative data on ibuprofen and other drugs. Ibuprofen ranked lowest or equal lowest for risk in 10 of the 11 studies. Pooled relative risks calculated with exposure to ibuprofen used as reference were all significantly greater than 1.0 (interval of point estimates 1.6 to 9.2). Overall, ibuprofen was associated with the lowest relative risk, followed by diclofenac. Azapropazone, tolmetin, ketoprofen, and piroxicam ranked highest for risk and indomethacin, naproxen, sulindac, and aspirin occupied intermediate positions. Higher doses of ibuprofen were associated with relative risks similar to those with naproxen and indomethacin.

Conclusions: The low risk of serious gastrointestinal complications with ibuprofen seems to be attributable mainly to the low doses of the drug used in clinical practice. In higher doses ibuprofen is associated with a similar risk to other non-steroidal anti-inflammatory drugs. Use of low risk drugs in low dosage as first line treatment would substantially reduce the morbidity and mortality due to serious gastrointestinal toxicity from these drugs.

Key messages

  • Because there are no important differences in efficacy, choice of first line treatment with these drugs should be based on their relative toxicity

  • Meta-analysis of the available epidemiological studies shows wide differences between individual drugs in the risk of inducing gastrointestinal bleed- ing and ulcer perforation

  • Of the drugs in common use, ibuprofen and diclofenac rank low in toxicity whereas azapropa- zone, ketoprofen, and piroxicam rank high

  • Some of the differences between drugs may be explained by dose, and the advantage of “low risk” drugs may be lost once their dose is increased

Footnotes

  • Funding Funding (other than above): None.

  • Conflict of interest None.

  • Accepted 12 April 1996

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