Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs

Background: Misoprostol is effective for ulcers associated with the use of nonsteroidal antiinflammatory drugs (NSAIDs) but is often poorly tolerated because of diarrhea and abdominal pain. We compared the efficacy of omeprazole and misoprostol in healing and preventing ulcers associated with NSAIDs. Methods: in a double-blind study, we randomly assigned 935 patients who required continuous NSAID therapy and who had ulcers or more than 10 erosions in the stomach or duodenum (or both) to receive 20 mg or 40 mg of omeprazole orally in the morning or 200 microg of misoprostol orally four times daily. Patients were treated for four weeks or, in the absence of healing, eight weeks. Treatment success was defined as the absence of ulcers and the presence of fewer than five erosions at each site and not more than mild dyspepsia. We then randomly reassigned 732 patients in whom treatment was successful to maintenance therapy with 20 mg of omeprazole daily, 200 microg of misoprostol twice daily, or placebo for six months. Results: at eight weeks, treatment was successful in 76 percent of the patients given 20 mg of omeprazole (233 of 308), 75 percent of those given 40 mg of omeprazole (237 of 315), and 71 percent of those given misoprostol (212 of 298). The rates of gastric-ulcer healing were significantly higher with 20 mg of omeprazole (but not 40 mg of omeprazole) than with misoprostol. Healing rates among patients with duodenal ulcers were higher with either dose of omeprazole than with misoprostol, whereas healing rates among patients with erosions alone were higher with misoprostol. More patients remained in remission during maintenance treatment with omeprazole (61 percent) than with misoprostol (48 percent, P=0.001) and with either drug than with placebo (27 percent, P<0.001). There were more adverse events during the healing phase in the misoprostol group than in the groups given 20 mg and 40 mg of omeprazole (59 percent, 48 percent, and 46 percent, respectively). Conclusions: the overall rates of successful treatment of ulcers, erosions, and symptoms associated with NSAIDs were similar for the two doses of omeprazole and misoprostol. Maintenance therapy with omeprazole was associated with a lower rate of relapse than misoprostol. Omeprazole was better tolerated than misoprostol

Overview of 50 years' progress in upper GI diseases

There have been numerous and dramatic advances in our understanding of the mechanisms, causes and treatments of upper gastrointestinal diseases in the past 50 years. This review focuses on a few, not dealt with elsewhere in this special issue of the Journal. The early history of the recognition that nonsteroidal anti-inflammatory drugs are a major cause of peptic ulcer is described, with particular attention to the work of the pioneering Australian investigators. The story of the development of the histamine H2-receptor antagonists and the proton pump inhibitors is also outlined

The ulcer sleuths : the search for the cause of peptic ulcers

The search for the cause or causes of peptic ulcers has been a long one. It was recognised as early as the 19th Century that damage to the stomach or duodenal bulb was likely to result if the resistance of their mucosae to luminal acid was for some reason impaired. An early theory suggested microscopic vascular occlusion leading to local infarction could be the initiating event but evidence was lacking. Excessive acid secretion is seen in some patients but not in many so is implausible as the main factor in most ulcers. Cigarette smoking is a risk factor and chronic life difficulties has been shown to sometimes play a part, but we would now think that they play only minor roles to possibly tip the balance when a major etiologic factor is already present. The overwhelming evidence now is that the major etiologic factors in chronic peptic ulcer are ingestion of nonsteroidal anti-inflammatory drugs (NSAIDs) and infection with Helicobacter pylori. Understanding the mechanism of the first, and the discovery and demonstration of Koch's postulates for the second, have been instrumental in the award of two Nobel prizes

Consensus about managing gastrointestinal and cardiovascular risks of nonsteroidal anti-inflammatory drugs?

In a recently published article in BMC Medicine, Scarpignato and colleagues present the results of a consensus conference that addressed several aspects of the management of pain in patients with osteoarthritis. The main areas covered include the relative safety in regard to gastrointestinal and cardiovascular adverse events of non-selective ‘traditional’ non-steroidal anti-inflammatory drugs (NSAIDs) versus cyclooxygenase-2 selective NSAIDs. The role of co-therapy with proton pump inhibitors in enhancing gastrointestinal safety is also reviewed. This commentary focuses on two areas that the consensus conference addressed, i) the whole length of gastrointestinal tract risk profile of the various NSAIDs (not just the ulcer risks in stomach and duodenum); ii) more recent information, but still some uncertainties, about the cardiovascular risks associated with the two classes of NSAID in general, and naproxen in particular

Aspirin : old drug, new uses and challenges

Salicylates have been used since antiquity to relieve pain and inflammation. However, it has been only in the last half century that evidence has emerged that aspirin causes reproducible acute and superficial injury to the gastric and duodenal mucosa, and is an important cause of complicated and uncomplicated peptic ulcer. Superficial damage to the mucosa occurs rapidly and reproducibly and acid and pepsin then produce a second wave of deeper injury. Most of the time this heals rapidly, but some focal deeper mucosal lesions (erosions) occur frequently and the point prevalence of frank ulcers in low dose aspirin users is around 10%. It is even more recently that aspirin's unique antiplatelet action has been recognized, with long-lasting inhibition of platelet aggregation due to irreversible inactivation of the cyclooxygenase-1 mediated production of thromboxane. It has now become the mainstay of pharmacological reduction of thrombotic risk in patients with cardiovascular diseases. In addition, evidence is accumulating about the cancer-reducing effects of blocking cyclooxygenase in a number of tissues. For example, recent data indicate that even at a 75-mg/day dose, it may reduce colorectal cancer risk after a lag of a year or so. Because of its widespread use for cardiovascular protection, aspirin is now one of the most frequently prescribed drugs-and gastroenterologists regularly need to deal with its ulcerative complications along the whole length of the gastrointestinal tract. Strategies that can be used to reduce these risks include using the lowest effective aspirin dose and co-prescribing acid suppressants

Health care in late Qing Dynasty and Republican China : Western influences, Chinese solutions

Western influences from about the middle of the 19th century played a pivotal role in modernising and improving health care in imperial and post-revolutionary China. But these influences also came up against the forces of a long medical tradition, cultural pride, and xenophobia. Much has been written about the “barefoot doctors” and the move to the countryside during the Cultural Revolution from the mid-1960s.1,2 This article explores the less well known period that preceded it

Impact of cyclooxygenase-2 inhibitors : are they fulfilling their promises?

Editorial: In this month’s issue of the Internal Medicine Journal, Joshua et al. analyse the patterns of use of the highly selective cyclooxygenase (COX)-2 inhibitors during the first 16 months of their release into the Australian market, and attempt a partial assessment of their costs and benefits.1 The COX-2 inhibitors were of course developed in the hope that the human and financial costs of non-steroidal anti-inflammatory drug (NSAID)- induced ulcers would be reduced, but also in the realisation that the drug costs of NSAID treatment would be bound to increase – at least while the new drugs have patent protection