The Changing Face of Peptic Ulceration

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used and some 24 million prescriptions are issued for them each year in the United Kingdom. Although animal and human experimental studies can yield confusing and disparate findings, complaints of gastro-intestinal side effects are common, and spontaneous reports of serious gastro-intestinal adverse effects of NSAIDs form by far the most commonly reported variety to the United Kingdom's Committee on the Safety of Medicines. Experimental suggestions that non-aspirin non-steroidal anti-inflammatory drugs (NSAIDs) cause gastritis and erosions have been overshadowed by evidence that takers of NSAIDs tend to develop serious complications with acute bleeding and perforations of duodenal and gastric ulcers. Findings in clinical case series that a third or more of patients with bleeding or perforated ulcers have been taking non-aspirin NSAIDs contrast with the outcome of surveillance studies where, in sets of 10,000 takers of such drugs, there appeared to be no material differences in ulcer complication rates in takers and non-takers. Data obtained in formal case control studies, however, have suggested a relative risk which is increased by between two-and four-fold in non-aspirin NSAID takers for both gastric and duodenal ulcer in elderly people. The findings in case-control and surveillance studies can be reconciled by taking account of the very large numbers of prescriptions for non-aspirin NSAIDs issued each year, now approaching 24 million in the United Kingdom. Some approximate calculations suggest that serious complications may occur about once in association with every 30,000 prescriptions in individuals aged under 60 and about once with every 3000 in those aged 60 and over. Surveillance studies in combined groups of younger and older people may therefore fail to detect any material risks although, given the intensity of non-aspirin NSAID use, such treatment may actually be responsible for at least 2000 hospital admissions each year in the United Kingdom with serious ulcer complications, and at least 200 deaths. The observations that non-aspirin NSAID treatment increases small bowel permeability to probe macro-molecules, and is associated with an increased frequency of lower bowel perforation and bleeding, suggest that the widely held belief that damage necessarily occurs against a background of acid-peptic attack is misplaced. In addition, a generally rising frequency of ulcer perforation in the elderly in the United Kingdom suggests that other environmental factors may be increasing susceptibility to gastro-intestinal mucosal damage in the elderly.

Key Words:

• Anti-inflammatory drugs
• duodenal ulcer
• epidemiology
• mortality
• peptic ulcer
• tobacco