Ulcer-healing drugs are required after eradication of Helicobacter pylori in patients with gastric ulcer but not duodenal ulcer haemorrhage

AIM: To study the efficacy of a 2-week anti-Helicobacter therapy in the healing of H. pylori-associated bleeding peptic ulcers. METHODS: Omeprazole 20 mg, clarithromycin 500 mg and amoxycillin 1 g, twice daily, were given for 2 weeks to 180 patients with H. pylori-associated bleeding peptic ulcers. Endoscopy was repeated 4 weeks after the eradication therapy to assess healing of the peptic ulcers. RESULTS: Repeat endoscopies were performed in 168 patients (42 gastric ulcer and 126 duodenal ulcer) who followed the protocol. Thirty-eight patients with bleeding gastric ulcers and 124 patients with bleeding duodenal ulcers healed 4 weeks after treatment (per protocol analysis; gastric ulcer: 91% vs. duodenal ulcer: 98%; P=0. 035). No patients who were compliant to the study medications suffered from re-bleeding. Stepwise discriminant analysis demonstrated that small ulcers (< 15 mm) and the presence of duodenal ulcers best predicted healing of the peptic ulcers. CONCLUSIONS: Ulcer-healing drugs should be continued after a 2-week course of omeprazole-containing anti-Helicobacter therapy for gastric ulcers and large peptic ulcers that have bled, but can be omitted in most patients with a bleeding duodenal ulcer.     

Omeprazole in peptic ulcers resistant to histamine H2-receptor antagonists

Eighteen patients with duodenal, gastric or jejunal ulcers, resistant to at least 3 months treatment with histamine H2-receptor antagonists, singly or in combination with other anti-ulcer drugs, were treated with 40 mg omeprazole once daily for up to 8 weeks. All ulcers healed, the majority within two weeks. After ulcer healing patients were given maintenance therapy with high doses of cimetidine or ranitidine. Of 15 patients on maintenance therapy with H2-receptor antagonists, 12 (80%) developed a relapse after a period ranging from 3 to 52 weeks. Two patients were lost to follow-up. After re-healing on 40 mg omeprazole, two patients were given 20 mg omeprazole daily as maintenance therapy but relapses occurred again after 14 and 26 weeks respectively. After re-healing on 40 mg omeprazole, these two patients and one additional patient received maintenance therapy with 40 mg omeprazole daily. At present these three patients have been relapse-free for periods varying from 16 to 52 weeks. No side effects were registered during treatment with omeprazole. It is therefore concluded that omeprazole is highly effective in healing refractory peptic ulcers and that omeprazole maintenance therapy may be useful for prevention of relapse. Patients are sometimes seen with peptic ulceration which appears resistant to therapy with histamine H2-receptor antagonists, colloidal bismuth subcitrate, sucralfate or pirenzepine, either given as monotherapy for a prolonged period of time or as combination therapy. Usually the reason for such therapeutic failure remains obscure. Whether virtually total abolition of acid secretion will allow ulcer healing in these circumstances is unknown.(ABSTRACT TRUNCATED AT 250 WORDS)     

Lansoprazole: pharmacokinetics, pharmacodynamics and clinical uses

Lansoprazole (Prevacid, TAP Pharmaceuticals, Inc.) is a substituted benzimidazole that inhibits gastric acid secretion. This agent is approved for the short-term treatment of erosive reflux oesophagitis, active gastric ulcer, active duodenal ulcer and the treatment of non-steroidal anti-inflammatory drug (NSAID)-induced gastric and duodenal ulcers. It is also approved for the long-term treatment of healed reflux oesophagitis, healed duodenal ulcer, the treatment of hypersecretory conditions such as Zollinger-Ellison syndrome and the eradication of Helicobacter pylori as a component of triple therapy with lansoprazole, clarithromycin and amoxicillin, or dual therapy with lansoprazole and amoxicillin. Its mechanism of action is to selectively inhibit the membrane enzyme H+/K+ ATPase in gastric parietal cells. In clinical trials, lansoprazole is more effective than placebo or histamine (H2)-receptor antagonists in the treatment of reflux oesophagitis. Lansoprazole administered at a dose of 30 mg daily produced faster relief of symptoms and superior healing rates in patients with gastric or duodenal ulcers or reflux oesophagitis than H2-receptor antagonists. A daily dose of 30 mg lansoprazole reduced epigastric pain faster than omeprazole 20 mg daily in patients with peptic ulcer disease but healing rates at 4 and 8 weeks were similar with both agents at these dosages. Lansoprazole was more effective than H2-receptor antagonists in patients with Zollinger-Ellison syndrome and produced similar treatment outcome to omeprazole. Lansoprazole in combination with clarithromycin and amoxicillin produced similar rates of eradication of H. pylori. In clinical trials, lansoprazole is well-tolerated and has a low frequency of side effects similar to that of H2-receptor antagonists or omeprazole.     

Lansoprazole: pharmacokinetics,pharmacodynamics and clinical uses

Lansoprazole (Prevacid?, TAP Pharmaceuticals, Inc.) is a substituted benzimidazole that inhibits gastric acid secretion. This agent is approved for the short-term treatment of erosive reflux oesophagitis, active gastric ulcer, active duodenal ulcer and the treatment of non-steroidal anti-inflammatory drug (NSAID)-induced gastric and duodenal ulcers. It is also approved for the long-term treatment of healed reflux oesophagitis, healed duodenal ulcer, the treatment of hypersecretory conditions such as Zollinger-Ellison syndrome and the eradication of Helicobacter pylori as a component of triple therapy with lansoprazole, clarithromycin and amoxicillin, or dual therapy with lansoprazole and amoxicillin. Its mechanism of action is to selectively inhibit the membrane enzyme H⁺/K⁺ATPase in gastric parietal cells. In clinical trials, lansoprazole is more effective than placebo or histamine (H₂)-receptor antagonists in the treatment of reflux oesophagitis. Lansoprazole administered at a dose of 30 mg daily produced faster relief of symptoms and superior healing rates in patients with gastric or duodenal ulcers or reflux oesophagitis than H₂-receptor antagonists. A daily dose of 30 mg lansoprazole reduced epigastric pain faster than omeprazole 20 mg daily in patients with peptic ulcer disease but healing rates at 4 and 8 weeks were similar with both agents at these dosages. Lansoprazole was more effective than H₂-receptor antagonists in patients with Zollinger-Ellison syndrome and produced similar treatment outcome to omeprazole. Lansoprazole in combination with clarithromycin and amoxicillin produced similar rates of eradication of H. pylori. In clinical trials, lansoprazole is well-tolerated and has a low frequency of side effects similar to that of H₂-receptor antagonists or omeprazole.     

Omeprazole. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in peptic ulcer disease and Zollinger-Ellison syndrome

Omeprazole is a substituted benzimidazole derivative which markedly inhibits basal and stimulated gastric acid secretion. It has a unique mode of action, irreversibly blocking the so-called proton pump of the parietal cell which is supposedly the terminal step in the acid secretory pathway. In animals, on a weight basis, omeprazole is 2 to 10 times more potent than cimetidine in inhibiting gastric acid secretion. Toxicological studies in rats have shown that very high doses of omeprazole administered for 2 years produce hyperplasia of gastric enterochromaffin-like cells and carcinoids, a few with proliferations into the submucosa. The significance of such findings to the clinical situation is wholly speculative and requires further research. Preliminary studies in patients with duodenal ulcers or Zollinger-Ellison syndrome have found no mucosal changes which would suggest that the drug represents a risk for development of carcinoid tumours at therapeutic dosages. In patients with duodenal ulcers omeprazole, at dosages of at least 20mg once daily, produced ulcer healing rates of between 60 and 100% after 2 weeks and between 90 and 100% after 4 weeks, even in patients resistant to treatment with H2-receptor antagonists. Comparative trials clearly demonstrated that omeprazole 20 to 40 mg administered once daily was significantly more effective than usual dosage regimens of cimetidine and ranitidine in healing duodenal ulcers during 2 to 4 weeks of treatment. At present no data are available evaluating omeprazole as maintenance therapy once ulcers have healed. Other clinical trials have also shown that omeprazole is effective for treating gastric ulcers, ulcerative peptic oesophagitis, and Zollinger-Ellison syndrome. In patients with Zollinger-Ellison syndrome the profound and long lasting antisecretory activity of omeprazole may make it the drug of choice for treating the massive acid hypersecretion associated with the disease, especially when H2-receptor antagonists are ineffective. During clinical trials reported to date omeprazole has been very well tolerated but further clinical experience is essential to fully evaluate its safety profile. Thus, omeprazole represents a pharmacologically unique antisecretory drug which is very effective for rapidly healing peptic ulcers and peptic oesophagitis, and for reducing gastric acid hypersecretion in patients with Zollinger-Ellison syndrome. If the apparent absence of undesirable mucosal morphological changes during treatment with usual doses in patients with peptic ulcer disease is confirmed, it may be a major advance in the treatment of these diseases.     

Rabeprazole: a review of its use in acid-related gastrointestinal disorders.

Rabeprazole is an inhibitor of the gastric proton pump. It causes dose-dependent inhibition of acid secretion and has a more rapid onset of action than omeprazole. Duodenal ulcers healed faster after treatment with rabeprazole 20 or 40 mg/day than placebo or ranitidine 150 mg 4 times daily and at a generally similar rate to omeprazole 20 mg/day in patients with duodenal ulcers; rabeprazole was similar or superior to these agents in relieving symptoms. Rabeprazole 20 and 40 mg/day healed gastric ulcers faster than placebo, and rabeprazole 20 mg/day healed ulcers at a similar healing rate, to omeprazole 20 mg/day in well controlled 6-week studies. Gastric ulcer symptom relief with rabeprazole was similar or superior to that provided by omeprazole or placebo. In 8-week studies in patients with gastro-oesophageal reflux disease (GERD), rabeprazole 10, 20 and 40 mg/day were more effective than placebo, rabeprazole 20 mg/day was more effective than ranitidine 150 mg twice daily, and rabeprazole 20 mg/day was similar in efficacy to omeprazole 20 mg/day. Symptom relief with rabeprazole in 8-week trials in patients with GERD was superior to that provided by placebo, and similar to ranitidine or omeprazole. Rabeprazole was similar to omeprazole and superior to placebo in both maintenance of healing and prevention of symptoms in patients with healed GERD in 1-year studies. One-week triple therapy with rabeprazole 20 mg twice daily plus 2 antibacterial agents achieved > or = 90% Helicobacter pylori eradication, but, as would be expected, a regimen of rabeprazole 20 mg twice daily plus 1 antibacterial agent was less successful. The drug was as effective as omeprazole and lansoprazole as part of triple therapy for H. pylori eradication. Rabeprazole successfully reduced acid output to target levels and prevented further pathological changes in 10 patients with Zollinger-Ellison syndrome. Usual dosages of rabeprazole are 20 mg/day for 4 weeks to treat duodenal ulcers, 6 weeks for gastric ulcers and 8 weeks for GERD, although some patients with duodenal ulcer may respond to a 10 mg/day dosage. For long term maintenance of GERD healing, 10 or 20 mg daily doses are adequate. Patients with hypersecretory states may need individualised dosages starting at 60 mg/day. The drug was well tolerated in clinical trials, with headache, rash, infection, diarrhoea and flu syndrome as the most common adverse events. In conclusion, rabeprazole appears to be a well tolerated proton pump inhibitor with a rapid onset of action and a low potential for drug interactions. The drug may be used to achieve healing and the relief of symptoms of duodenal ulcer, gastric ulcer and GERD, maintain GERD healing, and can form part of effective regimens to eradicate H. pylori.     

奥美拉唑治疗消化性溃疡的剂量与疗程分析

目的分析研究奥美拉唑对消化性溃疡的治疗剂量与疗程和疗效。方法将90例消化性溃疡患者随机分为两组,A组45例,用奥美拉唑20mg/d,治疗十二指肠溃疡4周,胃溃疡6周;B组45例用奥美拉唑40mg/d,治疗十二指肠溃疡2周,胃溃疡3周;两组患者均同时服用甲硝唑400mg,克拉霉素250mg,均2次/d。结果十二指肠溃疡的愈合率两组分别为84%和84%,胃溃疡的愈合率两组分别为85%和85%;十二指肠溃疡的总有效率两组分别为96%和96%,胃溃疡的总有效率两组均为100%,在愈合率与总有效率方面无明显差异。说明用奥美拉唑20mg/d,治疗时间要长,用奥美拉唑40mg/d,治疗时间则短,无论采取哪种方法,该药对消化性溃疡的治疗效果都是令人满意的。结论奥关拉唑对消化性溃疡的治疗效果是显著的,该药是质子泵抑制剂,能很好地抗胃酸分泌,迅速缓解症状,促进消化性溃疡的愈合。     

Lansoprazole: A Comprehensive Review

Lansoprazole is the second member of the substituted benzimidazole class of antisecretory agents approved for use in the United States. These drugs decrease parietal cell acid secretion by inhibiting H⁺,K⁺-adenosine triphosphatase, the final step in the secretion of acid. Lansoprazole has been studied extensively for the short-term treatment of duodenal and gastric ulcers, reflux esophagitis, and Helicobacter pylori-positive peptic ulcer disease; long-term treatment of Zollinger-Ellison syndrome; and maintenance treatment of erosive esophagitis. A dosage of 30 mg/day produced higher healing rates and equivalent or faster relief of ulcer symptoms than ranitidine or famotidine in patients with duodenal or gastric ulcers and reflux esophagitis. Compared with omeprazole 20 mg/day, that dosage provided faster epigastric pain relief in these patients after 1 week, although healing rates for the two agents were equivalent at 4 and 8 weeks. In patients with peptic ulcer refractory to 8-week therapy with histamine₂-receptor antagonists, healing rates were not significantly different between lansoprazole and omeprazole. In patients with Zollinger-Ellison syndrome, lansoprazole was superior to histamine₂-receptor antagonists and was similar in efficacy, safety, and duration of action to omeprazole. Combinations of lansoprazole or omeprazole with one or two antibiotics produced equivalent eradication of H. pylori. In clinical trials, lansoprazole was well tolerated, with frequency of adverse effects similar to that reported with ranitidine, famotidine, and omeprazole.     

One-week low-dose triple therapy for Helicobacter pylori is sufficient for relief from symptoms and healing of duodenal ulcers

Aim : To test the hypothesis that 1-week low-dose triple therapy for H. pylori is sufficient for relief from dyspeptic symptoms and healing of duodenal ulcers.
Methods : Fifty-nine out-patients with duodenal ulcers and positive rapid urease test participated in this randomized, double-blind, two-centre study. All patients were treated for 1 week with omeprazole 20 mg b.d., clarithromycin 250 mg b.d. and metronidazole 400 mg b.d. In a double-blind fashion, patients were then randomly treated for another 3 weeks with either omeprazole 20 mg once daily or an identical-looking placebo. Patients were investigated endoscopically before treatment for H. pylori , after 2 weeks and after 4 weeks. H. pylori infection was assessed by a ¹³C-urea breath test at the time of enrolment and 4 weeks after cessation of any study medication.
Results : Fifty-two patients were included in the 'all patients treated' analysis of efficacy. The overall H. pylori cure rate was 96% (95% CI=87–100%), with no difference between the treatment groups. After 2 weeks duodenal ulcer healing was confirmed in 91% (95% CI=80–100%) of patients treated with omeprazole and in 76% (95% CI=60–91%) in the placebo group ( P =0.14). After 4 weeks all ulcers had healed. Relief from dyspeptic symptoms and adverse events (13.8 and 16.7%) did not differ between the treatment groups.
Conclusions : One-week low-dose triple therapy consisting of omeprazole, clarithromycin and metronidazole is a highly effective and well-tolerated approach to the cure of H. pylori infection in patients with a duodenal ulcer. Our data suggest that continuation of antisecretory drug therapy beyond anti- H. pylori therapy is actually excessive regarding relief from dyspeptic symptoms and healing of duodenal ulcers.     

Lansoprazole. A review of its pharmacodynamic and pharmacokinetic properties and its therapeutic efficacy in acid-related disorders.

Lansoprazole is an effective acid pump inhibitor acting at the final enzymatic step of the acid secretory pathway of the parietal cell, decreasing gastric acid secretion regardless of the primary stimulus. Results of short term (less than 8 weeks) clinical trials have shown lansoprazole to be significantly superior to placebo and ranitidine in the treatment of duodenal ulcer, both in the rate of healing and in overall healing at 4 weeks. Lansoprazole appears to heal duodenal ulcer more quickly than famotidine, and demonstrates slightly greater efficacy at 4 weeks, although both drugs appear to have equivalent efficacy overall. Gastric ulcers and reflux oesophagitis are also healed by lansoprazole 30 mg/day for 4 to 8 weeks, with healing rates after 8 weeks of approximately 85 to 95% for both indications. Lansoprazole appears to be superior to ranitidine and comparable to omeprazole in treating reflux oesophagitis. Furthermore, lansoprazole has relieved reflux symptoms more quickly than either ranitidine or omeprazole. Preliminary data also indicate that lansoprazole may be effective in the treatment of peptic ulcer disease and reflux oesophagitis refractory to H2-receptor antagonists, and in patients with Zollinger-Ellison syndrome. While direct comparisons with omeprazole are limited, results suggest that lansoprazole, used for short term treatment, is at least as effective as omeprazole in the treatment of peptic ulcer and reflux oesphagitis. Lansoprazole has been well tolerated in short term clinical trials, with an incidence of adverse effects comparable with that of other agents in its therapeutic class. Trials assessing long term tolerability data are ongoing and will be required as part of the assessment of the safety profile, if lansoprazole is to be used prophylactically to prevent ulcer recurrence. Thus, by virtue of its ability to heal ulcers and rapidly relieve associated symptomatology, lansoprazole represents a useful alternative for the treatment of acid related disorders.     

The effects of omepmzole and cimetidine on duodenal ulcer healing and ihe relief of symptoms

In a Swedish double-blind multicentre study, omeprazole (30 mg o.m.) was compared with the H2-receptor antagonist cimetidine (400 mg b.d.) in 152 patients. Clinical assessments and laboratory investigations were carried out at 2 and 4 weeks, and again at 6 weeks in unhealed patients. Endoscopy was performed at 2 weeks, and again at 4 and 6 weeks in unhealed patients. The patients in the two groups were well-matched prior to treatment. Omeprazole was superior to cimetidine in ulcer-healing rate after 2, 4 and 6 weeks. After 2 weeks of treatment, 66% of the omeprazole- and 45% of the cimetidine-treated patients were healed (P = 0.02), after 4 weeks 97 and 84% (P = 0.01), and after 6 weeks 100 and 92% (P = 0.02), respectively. There was a more pronounced improvement in the patients' symptoms in the omeprazole group after 2 weeks (P = 0.05). Both drugs were well-tolerated, but there was a high prevalence of patients with adverse events in the cimetidine group (51%, compared to 30% of the omeprazole group; P = 0.02). A total of 125 patients were followed for 6 months after healing. The patients were investigated by endoscopy after 6 months, or whenever symptoms occurred. There was no significant difference in the rate of relapse within 6 months between the two treatment groups: 54% relapsed in the omeprazole group and 52% in the cimetidine group. In conclusion, 30 mg of omeprazole, given once daily, is superior to 400 mg of cimetidine twice daily in duodenal ulcer healing; but ulcer relapse in the two groups appears to be equivalent.     

Does eradication of Helicobacter pylori impair healing of nonsteroidal anti-inflammatory drug associated bleeding peptic ulcers? A prospective randomized study

Background:

Despite the widely accepted view that Helicobacter pylori is the most important cause of peptic ulcer disease, recent studies have suggested that the microbe protects against nonsteroidal anti-inflammatory drug (NSAID)-associated gastroduodenal lesions and promotes ulcer healing. We investigated the effects of H. pylori eradication on the healing of NSAID-associated bleeding peptic ulcers.

Methods:

Chronic NSAID users presenting with peptic ulcer haemorrhage underwent endoscopy to secure haemostasis and to document H. pylori infection by rapid urease test and culture. They were prospectively randomized to receive either omeprazole (20 mg once daily) for 8 weeks or a 1-week course of triple therapy (bismuth subcitrate 120 mg, tetracycline 500 mg, metronidazole 400 mg, all given four times daily) plus omeprazole (20 mg once daily) for 8 weeks. Endoscopy was repeated after 8 weeks. Final H. pylori status was determined by a ¹³C-urea breath test that was performed at least 4 weeks after discontinuation of omeprazole.

Results:

195 H. pylori-infected NSAID users, complicated by bleeding ulcers, were randomized to receive omeprazole alone (102) or triple therapy plus omeprazole (93). 174 patients returned for second endoscopy at 8 weeks (91 in the omeprazole group, 83 in the triple therapy group). Urea breath test was negative in 14% in the omeprazole group vs. 92% in the triple therapy group (P < 0.001). Complete ulcer healing was achieved in 88 (97%) patients in the omeprazole group and 77 (93%) in the triple therapy group (P = 0.31). On intention-to-treat analysis, ulcers were healed in 86% of the omeprazole group and 83% of the triple therapy group (P = 0.50). There was no significant difference in the healing rates of gastric or duodenal ulcers between the two groups.

Conclusion:

Eradication of H. pylori did not impair the healing of NSAID-associated bleeding peptic ulcers.

     

Misoprostol. A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of peptic ulcer disease

Misoprostol is an analogue of prostaglandin E1 and is the first synthetic prostaglandin analogue to be made available for the treatment of peptic ulcer disease. It inhibits gastric acid secretion in man, and there is also some evidence that it limits the extent of gastrointestinal damage induced by ulcerogenic agents in animals and healthy volunteers at doses lower than those required to inhibit acid secretion. This 'cytoprotective' activity has been explained by several mechanisms, but its contribution to the clinical efficacy of misoprostol in healing established ulcers is doubtful since the drug does not appear to be effective in healing peptic ulcers at non-antisecretory dosages. In clinical trials, ulcer healing has been reported in 60 to 85% of patients with duodenal ulcers and 32 to 54% with gastric ulcers receiving misoprostol 200 micrograms 4 times daily for 4 weeks--the recommended dosage. In comparative studies, the percentage of patients with healed ulcers after misoprostol (800 micrograms daily) was not significantly different from that with cimetidine (1200 mg daily), although there was greater pain relief with cimetidine. No study has yet been published concerning the use of misoprostol as maintenance therapy for the prevention of ulcer recurrence, and no long term tolerability data are available. However, in acute ulcer healing studies (2 to 12 weeks in duration) misoprostol has been well tolerated. Diarrhoea was the most commonly reported symptom, and this was only rarely of sufficient severity to interfere with treatment. No evidence of histopathological changes in the gastric mucosa induced by misoprostol have been reported in man. Evidence of uterine stimulant effects in women receiving misoprostol during the first trimester of pregnancy has resulted in the drug being contraindicated during pregnancy. Thus, misoprostol is a new type of antiulcer drug, providing an alternative approach to the therapy of peptic ulcer disease. It has been shown to be effective and well tolerated in the healing of both gastric and duodenal ulcers. Future studies need to identify the specific types of patients likely to obtain most benefit from treatment, in order to define more clearly the place of misoprostol in the treatment of these indications, as well as addressing the possibility of ulcer prevention with lower doses of misoprostol.     

Clopidogrel plus omeprazole compared with aspirin plus omeprazole for aspirin-induced symptomatic peptic ulcers/erosions with low to moderate bleeding/re-bleeding risk -- a single-blind, randomized controlled study

BACKGROUND: Clopidogrel causes significantly less symptomatic peptic ulcer disease and gastrointestinal bleeding than low-dose aspirin in average-risk patients. The gastrotoxicity of clopidogrel in patients with active peptic ulcer disease is unknown. AIM: To compare the incidence of unhealed ulcers in patients receiving clopidogrel or aspirin. METHODS: Patients with aspirin-induced peptic ulcer disease treated with omeprazole (20 mg/day) were randomized to receive clopidogrel (75 mg/day) or to continue with low-dose aspirin. Success was defined as ulcer/erosion healing at the eighth week. RESULTS: One hundred and twenty-nine patients were recruited (69 received clopidogrel and 60 continued with aspirin). Thirty-one (45%) in the clopidogrel group and 25 (42%) in the aspirin group had a minor gastrointestinal bleed. No ulcer showed an adherent clot or visible vessel. The distributions of peptic ulcer disease were similar in the clopidogrel and aspirin groups (gastric ulcer: 41% vs. 40%; duodenal ulcer: 10% vs. 12%; gastric ulcer + duodenal ulcer: 6% vs. 3%; gastritis: 32% vs. 37%; duodenitis: 4% vs. 7%; gastritis + duodenitis: 0% vs. 2%). Clopidogrel and aspirin were re-started after 0.86 +/- 1.79 and 0.44 +/- 1.60 days, respectively (P = 0.170). Three (4%) patients stopped clopidogrel due to drug rash. Using per protocol analysis, the treatment success rates of clopidogrel and aspirin were 94% (62/66) and 95% (57/60), respectively. CONCLUSIONS: In patients with aspirin-associated peptic ulcer disease of low to moderate grade, both early conversion from aspirin to clopidogrel and continuation of aspirin are safe.     

clinical aspects of Helicobacter pylori eradication therapy in peptic ulcer disease

Background and aims : Although the role of H. pylori in peptic ulcer disease is no longer in dispute, certain aspects of eradication therapy in this condition have yet to be settled. Uncertainties still surround the relationship between Helicobacter pylori status and ulcer healing, the efficacy of eradication therapy in alleviating acute symptoms and healing ulcers, and the prognosis after eradication with respect to recurrence of symptoms, ulcers and complications. The present literature review, encompassing studies published up to October 1995, specifically addresses these issues.
Results : Pooled data show that eradication therapy heals 90% of duodenal ulcers and 85% of gastric ulcers, while individual studies repeatedly confirm that it is more effective at healing ulcers than conventional treatment with anti-secretory drugs. Recent reports indicate that triple therapy regimens for 1 week, provided they include an anti-secretory drug, are sufficient to achieve high rates of healing and rapid symptom relief. A detailed analysis of the data, particularly those from studies reporting healing rates in relation to H. pylori status after eradication therapy, provides strong evidence that eradication of H. pylori produces ulcer healing. Follow-up studies show that ulcer recurrence and complications are rare after eradication treatment in patients with either gastric or duodenal ulcer disease. However, while ulcer symptoms are infrequent during follow-up, a proportion of patients appear to develop gastrooesophageal reflux after eradication.
Conclusions : H. pylori eradication is highly effective in promoting ulcer healing and preventing subsequent ulcer recurrence. These beneficial effects of eradication therapy are observed in patients with either gastric or duodenal ulcers which are associated with H. pylori infection.     

泮托拉唑治疗消化性溃疡临床疗效观察

目的：研究泮托拉唑与奥美拉唑治疗消化性溃疡的疗效及安全性。方法：经胃镜证实的消化性溃疡患者随机分成泮托拉唑组（治疗组）62例和奥美拉唑组（对照组）58例。治疗组泮托拉唑40mg,po,qn,对照组用药为奥美拉唑20mg,po,qn。十二指肠溃疡患者疗程4周,胃溃疡患者疗程6周。停药后均复查胃镜观察溃疡愈合情况。症状改善及副作用发生情况。结果：十二指肠溃疡的愈合率两组分别为92．1％和94．7％,胃溃疡的愈合率两组分别为91．7％和90％（P均〉0．05）。各项症状的改善情况两组无统计学差异。副作用的发生率两组分别为9．7％和8．6％（P〉0．05）。结论：泮托拉唑对消化性溃疡有较高的治愈率和良好的症状改善情况,其疗效和副作用与奥美拉唑相当。     

The treatment of "cimetidine resistant" peptic ulcers by ranitidine hydrochloride: a new histamine H2-receptor antagonist

Twelve patients with endoscopically confirmed peptic ulcers which had failed to heal despite standard cimetidine therapy were treated with 300 mg ranitidine hydrochloride daily for 4 to 8 weeks. Nine patients had complete symptomatic relief although the ulcer was found to have healed endoscopically in only six. Two patients derived no benefit from treatment and in 1 patient symptoms continued despite ulcer healing. Ranitidine would appear, therefore, to be of benefit in some "cimetidine resistant" patients.     

Symptom relief and duodenal ulcer healing with omeprazole or cimetidine

In a double-blind parallel-group study, 98 patients with symptomatic duodenal ulcer received omeprazole 20 mg o.m. and 91 cimetidine 800 mg nocte for 2 or, if then not healed, 4 weeks. After 2 weeks the healing rates on an intention-to-treat basis were: for omeprazole 62% and for cimetidine 33% (P less than 0.001), and at 4 weeks 85% and 61%, respectively (P less than 0.001). The proportions symptom-free at 2 weeks were 83% of the omeprazole and 63% of the cimetidine-group (P less than 0.01) and at 4 weeks 84% and 72% (P = 0.01). Patients receiving omeprazole took fewer antacid tablets than those receiving cimetidine. Patient tolerance of both drugs was similar and good. In the treatment of duodenal ulcer, omeprazole 20 mg o.m. gives faster symptom relief than cimetidine 800 mg nocte, as well as healing a greater proportion of ulcers within 2 and 4 weeks.     

Omeprazole. An updated review of its pharmacology and therapeutic use in acid-related disorders.

Omeprazole is the first of a new class of drugs, the acid pump inhibitors, which control gastric acid secretion at the final stage of the acid secretory pathway and thus reduce basal and stimulated acid secretion irrespective of the stimulus. In patients with duodenal or gastric ulcers, omeprazole as a single 20 mg daily dose provides more rapid and complete healing compared with ranitidine 150 mg twice daily or 300 mg at nighttime, or cimetidine 800 or 1000 mg/day. Patients poorly responsive to treatment with histamine H2-receptor antagonists respond well to omeprazole--most ulcers healed within 4 to 8 weeks of omeprazole 40 mg/day therapy. Omeprazole 20 or 40 mg/day has been administered as maintenance therapy for peptic ulcer disease for up to 5.5 years with very few ulcer recurrences. In patients with erosive or ulcerative oesophagitis, omeprazole 20 or 40 mg/day produces healing in about 80% of patients after 4 weeks, and is superior to ranitidine with respect to both healing and symptom relief. Healing rates of greater than 80% are achieved after 8 weeks in patients with severe reflux oesophagitis unresponsive to H2-receptor antagonists. Maintenance therapy with a daily 20 mg dose prevents relapse in about 80% of patients over a 12-month period. Omeprazole is considered to be the best pharmacological option for controlling gastric acid secretion in patients with Zollinger-Ellison syndrome. Daily dosages of 20 to 360 (median 60 to 70 mg successfully reduce basal acid output to target levels (less than 10 mmol/h or less than 5 mmol/h in patients with severe oesophagitis or partial gastrectomy) during treatment for up to 4 years. Omeprazole is well tolerated in short term studies (up to 12 weeks); the reported incidence of serious side effects (about 1%) being similar to that seen in patients treated with an histamine H2-receptor antagonist. The longer term tolerability of omeprazole has been investigated in patients treated for up to 5.5 years. Slight hyperplasia, but no evidence of enterochromaffin-like (ECL) cell dysplasia or neoplasia or ECL cell carcinoids has been reported. ECL cell carcinoids have been observed in rats after life-long treatment with high doses of omeprazole or ranitidine, or in rats with partial corpectomy; the weight of experimental evidence indicates that this is a result of prolonged hypergastrinaemia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Peptic ulcer in the elderly—a double-blind, short-term study comparing nizatidine 300 mg with ranitidine 300 mg

This was a randomized, double-blind, multicentre, short-term study comparing ranitidine and nizatidine at the standard dosages of 300 mg at bedtime. In 49 centres in Italy, all peptic ulcer patients aged over 65 years and with endoscopically documented acute disease were considered eligible for the study. Clinical check-ups were repeated every 3 weeks, while the endoscopic and biochemical assessments were scheduled at 6 and (in unhealed patients) 12 weeks. Statistics: chi-squared test, Fisher's exact test, Student t-test for unpaired data. The study included 170 duodenal ulcer and 75 gastric ulcer patients. Of these, 83/17 duodenal ulcer and 38/75 gastric ulcer patients were treated with nizatidine 300 mg and the remainder with ranitidine 300 mg. The groups were well-matched for common clinical data. Eight patients dropped out. Healing rates at 6 and 12 weeks were 81.9% and 91.5% for nizatidine-treated duodenal ulcer patients versus 78.1% and 94.2% for ranitidinetreated duodenal ulcer cases (P: N.S.); 6 and 12-week healing rates were 76.3% and 89.5% for nizatidinetreated gastric ulcer patients versus 67.6% and 83.8% for ranitidine-treated gastric ulcer patients (P: N.S.). No slow healing risk factors were found. Only minor adverse events were registered. In conclusion: ranitidine 300 mg and nizatidine 300 mg both proved effective and safe in the treatment of acute peptic ulceration in the elderly.