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 misoprostol3^–7 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