Intended for healthcare professionals

Education And Debate

Outcomes studies of drug induced ulcer complications: do we need them and how should they be done?

BMJ 2000; 321 doi: (Published 29 July 2000) Cite this as: BMJ 2000;321:291
  1. C J Hawkey (, professor
  1. Division of Gastroenterology, University Hospital, Queen's Medical Centre, Nottingham NG7 2UH
  • Accepted 4 May 2000

The hazards of non-steroidal anti-inflammatory drugs are considerable, and they result in the death of up to 2000 patients a year in the United Kingdom.1 2 Protective strategies that use the prostaglandin analogue misoprostol37 or proton pump inhibitors8 9 have been developed by using endoscopic evaluation. These strategies have been shown to reduce the incidence of clinically important events such as ulcer bleeding.10 11 The structure of primary care in the United Kingdom lends itself to such studies

Non-steroidal anti-inflammatories exert their therapeutic and toxic effects mainly by inhibiting the cyclo-oxygenase enzyme, which is involved in prostaglandin synthesis. There are two isoforms of cyclo-oxygenase: the constitutive cyclo-oxygenase-1 is principally responsible for mucosal protection and the inducible cyclo-oxygenase COX-2 principally contributes to disease.12 13 The recent discovery of these two forms has stimulated development of selective inhibitors of cyclo-oxygenase-2,14 of which rofecoxib and celecoxib are available for clinical use.15 16 Unlike standard non-steroidal anti-inflammatories, these selective drugs do not affect gastric mucosal prostaglandins17 and do not injure the stomach at clinical doses.18 19

Summary points

Long term use of non-steroidal anti-inflammatory drugs can cause stomach ulcers

Selective cyclo-oxygenase-2 inhibitors reduce the risk of ulcers

Most studies have been based on endoscopic findings rather than clinical outcomes

Outcome studies need to be large, and problems exist in evaluating clinical outcomes

Future studies need to have improved outcome definitions or could be conducted in primary care groups

Requirement for outcomes studies

Regulatory authorities have been reluctant to remove warnings about ulcer complications from patient labels even though endoscopic studies show no …

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