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Acid-related disorders and use of antisecretory medication.

BACKGROUND The use of antisecretory medication (H2 blockers and proton pump inhibitors) is increasing rapidly, and constitutes 4-11% of the medical budget in the UK, Denmark and other western countries (1-6). The increasing use of proton pump inhibitors has aroused concern regarding the economic consequences (4-8). However, our knowledge about the type of patients who actually use antisecretory medication, why they use it, the consequences of use and understanding of the factors related to increasing use is sparse. In 1993, the approved main indications for use of antisecretory medication was oesophagitis and peptic ulcer disease. From 1995, they were approved as a part of H. pylori eradication treatment, and from 1997 they were approved as treatment for symptomatic reflux disease (www.produktresume.dk) (9). Numerous randomized trials have proven the high efficacy of antisecretory medication for treatment of peptic ulcer, gastro-oesophageal reflux disease and as a part of H. pylori eradication therapy (10-18). Antisecretory medication has been recommended for treatment of dyspeptic patients, and as primary prophylactic treatment in patients who use NSAIDs, but evidence for their efficacy in these settings is less convincing (19-21). Dyspeptic symptoms are common in the general population and affect within one year 25-54% of all adults, but only few of these seek medical care (22-30). Among patients who seek medical care dyspepsia is a chronic, relapsing condition with significant impact on the use of health care resources (31, 32). The main findings in dyspeptic patients are functional dyspepsia (>50%), peptic ulcer disease (20%), gastro-oesophageal reflux (20-30%) or gastric carcinoma (< 2%) (33). As peptic ulcers are cured after successful H. pylori eradication, strategies based on H. pylori testing have been proposed for management of dyspeptic patients as well as for patients who use anti-secretory medication on a long-term basis (34, 35). Alternative management strategies for dyspeptic patients are based on empiric antisecretory medication and/or prompt endoscopy. None of these strategies have ousted the others, and the most cost-effective approach to the initial assessment and management of dyspepsia is controversial (36). Many patients with gastro-oesophageal reflux disease suffer from heartburn, but patients with gastro-oesophageal acid reflux present in a wide clinical spectrum, ranging from no symptoms to debilitating symptoms and from no mucosal lesions, through erosive oesophagitis to severe lesions as Barrett’s oesophagus or oesophageal stricture (37-40). In western countries, 10-20% of the population experience heartburn and/or regurgitation at least once per week, but a clear demarcation between physiological reflux symptoms and gastro-oesophageal reflux disease has not been established (38-47). Although dyspeptic and reflux symptoms are highly prevalent, recent epidemiological descriptions of peptic ulcer and gastrooesophageal reflux disease are sparse, and it is unknown if the increasing use of antisecretory medication is related to a changing occurrence of these acid-related conditions (2-6, 38, 39, 48-66). Until 1999, the recommended strategy for management of dyspeptic patients in our area was prompt endoscopy. From 1999, a H. pylori test-and-treat strategy was recommended for patients < 45 years with no “alarm” symptoms. In spite of the recommended management strategies, many of the dyspeptic patients with no doubt have been managed by empiric treatment with antisecretory medication (30, 67, 68). About 1% of the dyspeptic patients in primary care have gastro-oesophageal cancer, and pre-endoscopic treatment with antisecretory medication might delay detection of the cancers (69-71). The extent of this is unknown. A few case reports have demonstrated that treatment with proton pump inhibitors can temporarily heal macroscopic lesions of early gastric cancers, and might thereby increase the risk of overlooking early cancers at endoscopy (72, 73). It is feared that pre-endoscopic treatment with antisecretory medication increases the risk of overlooking gastro-oesophageal cancer at endoscopy, but the absolute risk is unknown (70). Barrett’s oesophagitis is more common among patients with gastro-oesophageal reflux disease than in the background population (46, 74-77). The risk of osophageal adenocarcinoma is strongly increased among patients with Barrett’s oesophagus, with an incidence of oesophageal adenocarcinoma of 0.4-0.5% per year (7880). Several population-based studies have found that the risk of oesophageal adenocarcinoma is increased in patients with reflux disease, but the contribution of Barrett’s oesophagus to these risk estimates is unknown (37, 71, 81-85).