No clear winner in MEDAL race

Abstract

AbstractPrescribing an anti‐inflammatory medication is becoming an increasingly complicated therapeutic decision. This editorial will explore whether the recently published results of the Multinational Etoricoxib and Diclofenac Arthritis Long‐term (MEDAL) studies help to inform that decision.1 First of all, it is worth reviewing the convoluted background that has been reported as much in the newspapers and financial press as in the medical journals.It was in the 1990s that unacceptable rates of GI toxicity were linked with NSAIDs. MacDonald et al estimated that someone aged over 50 years taking an NSAID had a 0.7 per cent risk of a bleeding or perforated ulcer per year,2 and one out of three of these ulcers would be directly attributable to the drug. Assuming a mortality of 10 per cent it was estimated that NSAID therapy might account for 1200 deaths per year in the UK.Impressive scientific discoveries showed that benefits and toxicity could possibly be separated. Inhibition of cyclo‐oxygenase‐1 (COX‐1) was found to be the mechanism of GI toxicity, whereas a separate enzyme (COX‐2) mediated the suppression of inflammation. This paved the way for the pharmaceutical companies to develop drugs to selectively inhibit COX‐2. These coxib drugs still caused dyspepsia, but they did not seem to carry the serious GI risks of standard NSAIDs. Admittedly, arguments did rage over the reporting of results for celecoxib (Celebrex) and the lessening of the safety advantage by concomitant low‐dose aspirin.At this exciting stage COX‐2 inhibitors were also being considered for treatment of other diseases. The hope that cognitive decline in Alzheimer's disease might be slowed proved unfounded, however.3 Although rofecoxib and celecoxib did reduce the rate of recurrence of colorectal polyps,4 the three‐year studies against placebo provided a unique dataset to identify other long‐term side‐effects, including a fourfold increase in cardiovascular thrombotic events with rofecoxib.5 Amid a flurry of publicity rofecoxib was withdrawn, and safety warnings were sent to all doctors in the UK about COX‐2 inhibitors as a class. Litigation cases were brought, confidence fell and so did share prices. Copyright © 2007 Wiley Interface Ltd