Peptic ulcer is the most common cause of acute hemorrhage in the upper gastrointestinal tract, accounting for about 50 percent of cases1–14. There are approximately 150,000 hospitalizations per year in the United States for evaluation and treatment of bleeding ulcers (based on 1985 estimates and excluding federal hospitals)15. Although hospitalization and surgery for uncomplicated ulcers have decreased in the United States and Europe over the past 20 to 30 years, the number of hospital admissions for hemorrhage associated with ulcers has remained relatively unchanged15–17. It is noteworthy that the incidence of bleeding ulcers appears to . . .

Bleeding peptic ulcer.

Objective: To evaluate the long-term efficacy and safety of omeprazole in patients with gastroesophageal reflux disease resistant to treatment with histamine-2 (H2)-receptor antagonists. Design: Co...

Long-Term Treatment with Omeprazole for Refractory Reflux Esophagitis: Efficacy and Safety

Background: Data are limited on the value of effective antisecretory therapy in the relief of heartburn in patients without oesophagitis. Methods: Patients with heartburn, without endoscopic signs of oesophagitis, were randomized to double-blind treatment with omeprazole, 20 or 10 mg once daily, or placebo, for 4 weeks (n = 509). Pre-treatment oesophageal acid exposure was assessed using 24-h intra-oesophageal pH monitoring. Heartburn was assessed at 2 and 4 weeks. Results: At 4 weeks the proportion of patients with complete absence of heartburn was 46% (95% confidence interval, 39-53%) with 20 mg omeprazole, 31% (25-38%) with 10 mg omeprazole, and 13% (7-20%) with placebo. Satisfaction with therapy was reported by 66%, 57%, and 31% of the patients, respectively. Conclusions: Omeprazole, 20 and 10 mg once daily, provides rapid relief of heartburn in patients without endoscopic oesophagitis.

Heartburn without Oesophagitis: Efficacy of Omeprazole Therapy and Features Determining Therapeutic Response

Gastro-oesophageal reflux disease

Omeprazole blocks the action of H+,K+-ATPase in the gastric mucosa and thus inhibits the secretion of hydrochloric acid. We conducted a double-blind multicenter study (45 centers in 13 countries) of 602 patients with benign gastric or prepyloric ulcers to compare the effectiveness of omeprazole (20 mg once daily, 203 patients, or 40 mg once daily, 194 patients) and ranitidine, an H2-receptor antagonist (150 mg twice daily, 205 patients) in promoting ulcer healing and to evaluate the pattern of ulcer relapse during a six-month follow-up. Healing occurred at four weeks in 80 percent of the patients receiving 40 mg of omeprazole, 69 percent of those receiving 20 mg of omeprazole, 69 percent of those receiving ranitidine. At eight weeks, the corresponding figures were 96, 89, and 85 percent. A multivariate analysis of ulcer healing showed that at four weeks the ulcers of significantly more patients receiving omeprazole had healed as compared with patients receiving ranitidine (omeprazole, 40 mg, vs. ranitidine, P less than 0.0005; omeprazole, 20 mg, vs. ranitidine, P = 0.01). At eight weeks, the 40-mg dose of omeprazole was significantly more effective than ranitidine (P = 0.001) or the 20-mg dose of omeprazole (P = 0.03). Ulcer symptoms were relieved faster with omeprazole. In 68 patients receiving concurrent nonsteroidal antiinflammatory drugs, the healing rates at four weeks were 81 percent in the group receiving 40 mg of omeprazole, 61 percent in the group receiving 20 mg, and 32 percent in the group receiving ranitidine; at eight weeks, the corresponding figures were 95, 82, and 53 percent. During the six-month follow-up period (without treatment), significantly more patients in the omeprazole groups were free of symptoms and ulcers than in the ranitidine group. We conclude that in the dose used, omeprazole is superior to ranitidine in the treatment of benign gastric ulcers.

Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer.

One hundred and sixty two patients with endoscopically proved reflux oesophagitis stratified for severity, 66 with grade 1 disease (erythema and friability) and 96 with grade 2 or 3 disease (including erosions or ulcerations), were allocated at random to double blind treatment with omeprazole 40 mg in the morning or ranitidine 150 mg twice daily for up to 12 weeks. A patient could be evaluated sooner if symptomatic relief and endoscopically normal mucosa (grade 0) were noted after four to eight weeks' treatment. Patients treated with omeprazole responded significantly more rapidly than those treated with ranitidine (p less than 0.0001), cumulative healing rates at four, eight, and 12 weeks being 90%, 100%, and 100% respectively for those with grade 1 disease and 70%, 85%, and 91% respectively for those with grade 2 or 3 disease in the omeprazole group. Corresponding rates in the ranitidine group were 55%, 79%, and 88% (grade 1) and 26%, 44%, and 54% (grade 2 or 3). Relief of the major symptoms of heartburn, regurgitation, and dysphagia and improvements in the histological appearance of the mucosa occurred earlier and were again more pronounced during treatment with omeprazole than with ranitidine. This observed superiority of omeprazole 40 mg in the morning over ranitidine 150 mg twice daily in the short term treatment of reflux oesophagitis was obtained without major clinical or biochemical side effects, but further research is needed into longer term use of omeprazole and the effects of the acid inhibition it induces.

https://www.bmj.com/content/bmj/296/6615/89.full.pdf

Omeprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial.

One hundred and eighty patients with endoscopically proved duodenal ulcers were allocated at random to double blind treatment with the synthetic dehydroprostaglandin E2 enprostil 35 micrograms twice daily or ranitidine 150 mg twice daily for up to six weeks. Patients completed the study if ulcer healing and pain relief had occurred at two or four weeks. A total of 163 patients completed the trial. The duration of treatment was longer in the enprostil group (p less than 0.005) and the cumulative healing rates at two, four, and six weeks were 51%, 74%, and 85%, respectively. In the ranitidine group the corresponding figures were 65% (p less than 0.04), 89% (p less than 0.02), and 99% (p less than 0.002). More patients treated with ranitidine reported relief of pain (p less than 0.004 at weeks 5 and 6). The observed superiority of ranitidine 150 mg twice daily over enprostil 35 micrograms twice daily questions the clinical relevance of using so called "cytoprotection" as treatment for duodenal ulcer disease in the short term.

Enprostil and ranitidine in duodenal ulcer healing: double blind comparative trial.

We conducted a six week double blind randomised study of 176 patients with prepyloric gastric ulcer to determine whether the proton pump inhibitor, omeprazole 30 mg daily would accelerate healing and pain relief, as compared with cimetidine 1 g daily. At two, four, and six weeks after entry ulcers healed in a larger percentage of patients treated with omeprazole (54, 81, and 86%) than of those treated with cimetidine (39, 73, and 78%) ('intention to treat' cohort; p less than 0.05 at two weeks). A higher proportion of patients on omeprazole became free of pain during the first week of treatment (p less than 0.05). No major clinical or biochemical side effects were noted. Omeprazole is an efficient treatment for patients with prepyloric gastric ulcers.

https://gut.bmj.com/content/gutjnl/29/2/249.full.pdf

Effect of omeprazole and cimetidine on prepyloric gastric ulcer: double blind comparative trial

One hundred and forty two patients with duodenal ulcer who after a short term study had relief of pain and healed ulcers proved endoscopically were allocated at random to double blind maintenance treatment with enprostil (a synthetic dehydroprostaglandin E2) 35 micrograms or ranitidine 150 mg at bedtime for up to 12 months. Patients were monitored every third month and examined by endoscopy at three, six, and 12 months, or more often if warranted. The cumulative relapse rates in the enprostil group at three, six, and 12 months were 37% (25/67), 56% (37/66), and 62% (41/66), respectively. The corresponding rates in the ranitidine group were 8% (6/71), 19% (13/69), and 29% (20/69). These differences were highly significant and further enhanced by life table analysis adjusting for withdrawals and by an "intention to treat" analysis in which absence of proof of non-recurrence was counted as failure, more patients in the enprostil group having been withdrawn because of adverse events or recorded as non-compliant with the protocol. Enprostil 35 micrograms at bedtime cannot be recommended for preventing relapse of duodenal ulcer. Furthermore, the results challenge the clinical relevance of using so called "cytoprotection" for preventing recurrence.

https://www.bmj.com/content/bmj/294/6577/932.full.pdf

Enprostil and ranitidine in prevention of duodenal ulcer relapse: one year double blind comparative trial.

Oral ketoconazole appreciably reduced the rate of isolation of the outbreak strain from both systemically infected and colonised patients. The outbreak strain did not reappear when ketoconazole was withdrawn. All cases of systemic candidiasis acquired in the unit before April 1984 were caused by the outbreak strain, whereas after May 1984 all cases were caused by other strains. Control of an outbreak depends on its identification and the prevention of cross infection. Existing handwashing reagents can be replaced with fungicidal disinfectants such as Hibisol or Betadine, and antifungal prophylaxis can be given. Recent work in neutropenic patients in whom infection was probably due to an endogenous isolate showed that ketoconazole was as effective as amphotericin B, and prophylaxis with either agent failed.5 In this study ketoconazole failed in six cases, perhaps because of poor absorption in the gut as five patients had undergone major gastrointestinal surgery. Treatment with ketoconazole resulted in the virtual elimination of the outbreak strain, the incidence of cases returning to its former value, with occasional cases caused by the patients' own yeast flora. A much shorter course of prophylaxis might have been equally effective and could be considered in any unit where the incidence of candidal sepsis is unacceptably high and cross infection a problem.

https://www.bmj.com/content/bmj/291/6502/1093.full.pdf

L S Laursen

Papers

Omeprazole and ranitidine in treatment of reflux oesophagitis: double blind comparative trial.

Enprostil and ranitidine in duodenal ulcer healing: double blind comparative trial.

Effect of omeprazole and cimetidine on prepyloric gastric ulcer: double blind comparative trial

Enprostil and ranitidine in prevention of duodenal ulcer relapse: one year double blind comparative trial.

Controlled trial of arbaprostil in bleeding peptic ulcer.