Proton pump inhibitor therapy for peptic ulcer bleeding: Cochrane collaboration meta-analysis of randomized controlled trials

OBJECTIVE: To evaluate the efficacy of proton pump inhibitors (PPIs) in treating peptic ulcer bleeding. MATERIAL AND METHODS: We searched the MEDLINE, EMBASE, CENTRAL, Cochrane Library, and metaRegister of Controlled Trials databases and published proceedings of major meetings through November 2004 for randomized controlled trials that compared oral or intravenous PPIs with placebo or a histamine2-receptor antagonist for peptic ulcer bleeding. Pharmaceutical companies and relevant experts were contacted. Data extraction and assessment of study validity were performed independently in duplicate. Assessed outcomes were 30-day all-cause mortality, rebleeding, surgery, and repeated endoscopic treatment. Influence of study characteristics on outcomes was examined by subgroup analyses and meta-regression. RESULTS: We included 24 trials (4373 participants). Statistical heterogeneity was evident only for rebleeding. Treatment with PPIs had no significant effect on mortality (odds ratio [OR], 1.01; 95% confidence interval [CI], 0.74-1.40; number needed to treat [NNT], incalculable) but significantly reduced rebleeding (OR, 0.49; 95% CI, 0.37-0.65; NNT, 13) and the need for surgery (OR, 0.61; 95% CI, 0.48-0.78; NNT, 34) and repeated endoscopic treatment (OR, 0.32; 95% CI, 0.20-0.51; NNT, 10). Results were similar when analysis was confined to trials with adequate allocation concealment. Treatment with PPIs significantly reduced mortality in Asian trials (OR, 0.35; 95% CI, 0.16-0.74; NNT, 34) and in patients with active bleeding or a nonbleeding visible vessel (OR, 0.53; 95% CI, 0.31-0.91; NNT, 50). CONCLUSIONS: In ulcer bleeding, PPIs reduce rebleeding and the need for surgery and repeated endoscopic treatment. They improve mortality among patients at highest risk.     

Proton pump inhibitor for maintenance therapy of peptic ulcer]

The strategy for peptic ulcer therapy has been changing with the clinical application of the gastric proton pump inhibitor (PPI). In Japan, Miyoshi et al and Takemoto et al reported an earlier reepithelialization of peptic ulcer with omeprazole (OME) or lansoprazole (LAN) than famotidine (FAM). Miyoshi et al also reported that there was no significant difference between OME and FAM in ulcer relapse rate during a one year follow-up period. Therefore, there were two problems. One is application of PPI for prevention of ulcer relapse, and the other is the more accurate diagnosis of ulcer healing. Application of PPI for maintenance therapy is not yet realized in Japan, but, Lauritsen et al had already reported on the efficacy and safety of OME, 20 mg, three days a week and 10 mg, daily in prevention of duodenal ulcer relapse. Reepithelialization (red scar) is already established as a starting point of maintenance therapy, and from Miyake's report, a white scar is believed a favorable (non relapsing) end point.     

Meta-analysis of proton pump inhibitors in treatment of bleeding peptic ulcers.

OBJECTIVE: To evaluate the efficacy of proton pump inhibitors (PPIs) compared with placebo and histamine receptor antagonists (H2RAs) for reducing the incidence of rebleeding, surgery, and death in acute gastrointestinal bleeding (GIB) associated with peptic ulcer disease. DATA SOURCES: A systematic search of the English-language literature was performed using MEDLINE, EMBASE, and Pre-MEDLINE (from 1966 to September 2000) and a manual search of references. STUDY SELECTION: Randomized, controlled trials evaluating any PPI for acute GIB in adults with the end points of rebleeding, surgery of death. DATA SYNTHESIS: Nine trials (1829 pts.) were included. The relative odds of rebleeding indicated a 50% reduction in the PPI-treated group (OR 0.50, 95% CI 0.33 to 0.77; p = 0.002, NNTB 9; 95% CI NNTB 6 to 13). The relative odds of surgery indicated a 53% reduction in the PPI-treated group (OR 0.47, 95% CI 0.29 to 0.77; p = 0.003; NNTB 17, 95% CI 12 to 35). The relative odds for mortality indicated a nonsignificant 8% decrease in the odds of death in the PPI-treated group (OR 0.92, 95% CI 0.46 to 1.83, p = 0.81; NNTB 323, 95% CI NNTB 47 to infinity to NNTH 33). CONCLUSIONS: PPIs are superior to H2RAs and placebo in preventing rebleeding and the need for surgery in patients with GIB, although they do not appear to reduce mortality.     

Proton-pump inhibitors for acute peptic ulcer bleeding

OBJECTIVE: To review the use of proton-pump inhibitors for acute peptic ulcer bleeding. DATA SOURCES: Articles were obtained through computerized searches of MEDLINE (1966-September 2000). Additionally, several textbooks containing information on the diagnosis and management of acute peptic ulcer bleeding were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references. STUDY SELECTION: All randomized studies and pharmacoeconomic evaluations that used proton-pump inhibitor therapy for acute peptic ulcer bleeding were included. Randomized controlled trials and meta-analyses involving other therapies for treating peptic ulcer bleeding were also reviewed for possible inclusion. DATA EXTRACTION: The primary outcomes extracted from the literature were persistent or recurrent bleeding, transfusion requirements, need for endoscopic intervention or surgery, length of stay, and mortality. DATA SYNTHESIS: Data from double-blind, placebo-controlled trials involving more than 1000 patients demonstrate that short-term, high-dose omeprazole therapy is effective for reducing bleeding and transfusion requirements in patients with acute peptic ulcer bleeding. The patients most likely to benefit from this therapy are hospitalized patients at high risk for rebleeding and patients in whom endoscopic evaluation must be delayed or is unavailable. CONCLUSIONS: Omeprazole (and likely other proton-pump inhibitors) is useful in reducing bleeding and transfusion requirements in patients with acute peptic ulcer bleeding, although better delineation of appropriate candidates is needed.     

大剂量质子泵抑制剂泵入联合内镜下止血治疗老年消化性溃疡出血

目的探讨老年消化性溃疡出血的治疗方案。方法选取2014年1至12月于我院住院的85例老年消化性溃疡出血的患者,随机分为两组,观察A组(42例),入院后即给予内镜检查,如果为出血性溃疡,即给予内镜下止血治疗,后给予质子泵抑制剂(PPI)静脉滴注bid 5 d;观察B组(43例),入院后给予大剂量PPI(80 mg+8 mg/h)泵入治疗24 h后,再行内镜检查,如果内镜发现为出血性溃疡,即给予内镜下止血治疗,后再予PPI泵入72 h,观察1周,比较两组的快速止血率、溃疡的内镜下分级、内镜下治疗率及溃疡再出血率。结果观察A组具有较高快速止血率(100%),内镜下Forrest分级多为Ⅰa~Ⅱb(76.2%),高危溃疡率及内镜下治疗率(76.2%)明显高于观察B组(P<0.01),但两组再出血率无统计学差异。结论内镜下止血治疗对老年消化性溃疡出血疗效肯定,具有安全、快速止血、低再出血率的特点,提高了内科治疗效果;但首先给予大剂量、高效PPI泵入也能得到良好的治疗效果,不仅可减少高危溃疡的发生率及内镜下治疗率,而且可以减少患者内镜下检查的时间、内镜带来的痛苦及检查的费用,也是一种理想的治疗方案。     

Cost-effective prescribing of proton pump inhibitor therapy: an audit in general practice

General practitioners must prescribe cost effectively to control drug expenditure and provide optimal treatment for patients requiring long-term management. An audit was implemented in general practices to review the management of dyspepsia, improve care, rationalise therapy and reduce costs. Policy included identifying patients receiving proton pump inhibitor (PPI) therapy and changing to low-dose cost-effective therapy. If PPI therapy was not required, patients were changed to antacids, H2 receptor antagonists or no treatment. This was an audit in general practice, not a clinical trial, therefore findings reflect outcomes in normal clinical practice. This paper describes the implementation and findings of the audit between January 1997 and July 1999 in 91 general practices involving 7121 patients. Extrapolation of the results concluded that savings of up to 50,000 Pounds could be made in a practice of 10,000 patients, allowing reinvestment in health improvement plans and optimal care.     

Pantoprazole: a new proton pump inhibitor

OBJECTIVE: This paper reviews the pharmacology, clinical efficacy, and tolerability of pantoprazole in comparison with those of other available proton pump inhibitors (PPIs). METHODS: Relevant English-language research and review articles were identified by database searches of MEDLINE, International Pharmaceutical Abstracts, and UnCover, and by examining the reference lists of the articles so identified. In selecting data for inclusion, the author gave preference to full-length articles published in peer-reviewed journals. RESULTS: Like other PPIs, pantoprazole exerts its pharmacodynamic actions by binding to the proton pump (H+,K+ -adenosine triphosphatase) in the parietal cells, but, compared with other PPIs, its binding may be more specific for the proton pump. Pantoprazole is well absorbed when administered as an enteric-coated, delayed-release tablet, with an oral bioavailability of approximately 77%. It is hepatically metabolized via cytochrome P2C19 to hydroxypantoprazole, an inactive metabolite that subsequently undergoes sulfate conjugation. The elimination half-life ranges from 0.9 to 1.9 hours and is independent of dose. Pantoprazole has similar efficacy to other PPIs in the healing of gastric and duodenal ulcers, as well as erosive esophagitis, and as part of triple-drug regimens for the eradication of Helicobacter pylori from the gastric mucosa. It is well tolerated, with the most common adverse effects being headache, diarrhea, flatulence, and abdominal pain. In clinical studies, it has been shown to have no interactions with various other agents, including carbamazepine, cisapride, cyclosporine, digoxin, phenytoin, theophylline, and warfarin. CONCLUSIONS: Pantoprazole appears to be as effective as other PPIs. Its low potential for drug interactions may give it an advantage in patients taking other drugs.     

Endoscopic band ligation for control of acute peptic ulcer bleeding

BACKGROUND AND STUDY AIMS: The use of endoscopic band ligation (EBL) is being extended to treat various causes of upper and lower gastrointestinal bleeding. The aim of this study was to evaluate the usefulness of EBL for control of acute peptic ulcer bleeding and to define the lesions that are most suitable for this technique. PATIENTS AND METHODS: 19 patients with major stigmata of acute peptic ulcer bleeding were treated using EBL; 11 patients had active bleeding and eight patients had a nonbleeding visible vessel. RESULTS: The site of acute peptic ulcer bleeding was the stomach in 12 patients, the duodenum in four patients, and Billroth II anastomosis in three. Initial hemostasis was achieved in 19 patients (100 %) in a single session. There were no rebleeding episodes in any of the patients, and there was no bleeding-related or procedure-related death. During long-term outpatient follow-up, bleeding did not recur. CONCLUSIONS: EBL is an effective and safe endoscopic treatment for small-sized nonfibrotic acute peptic ulcer bleeding. Larger studies in patients with acute peptic ulcer bleeding are needed to confirm these promising results.     

质子泵抑制剂对经皮冠状动脉介入治疗术后双联抗血小板治疗致胃肠道出血的影响

目的 观察质子泵抑制剂(PPIs)能否对经皮冠状动脉介入治疗(PCI)术后双联抗血小板治疗所致胃肠道出血以及可能性支架血栓的发生产生影响,并进一步筛查PCI术后发生胃肠道出血及可能性支架血栓的危险因素.方法 选取62例在PCI术后双联抗血小板治疗并最终发生胃肠道出血的患者,并按性别、年龄、居住地、民族等为配比条件选取最终未发生胃肠道出血的患者123例进行1∶2配对病例对照研究.分别统计PCI术后1个月及6个月内发生胃肠道出血的情况,并用同样方法从该人群中选取41例在PCI术后双联抗血小板治疗并最终发生可能性支架血栓的患者及82例最终未发生支架血栓的患者进行1∶2配对病例对照研究.分别统计PCI术后1个月及6个月内发生可能性支架血栓的情况.结果 危险因素分析表明,与未使用PPIs相比,PCI术后联合使用PPIs发生胃肠道出血的相对危险度(OR)明显降低[OR=0.120,95%可信区间(CI)为0.055～0.262];使用PPIs治疗1个月与6个月相比,发生上消化道出血的危险无明显差异(P>0.05).此外,PCI术后发生胃肠道出血还与既往胃肠复合疾病史关系密切(OR=3.520;95%CI为1.253～9.889).在可能性支架血栓方面,PCI术后有无联合使用PPIs治疗及治疗时间的长短,与发生支架血栓的危险无明显差异(P>0.05); 而肾功能不全、既往心肌梗死病史、血小板计数增高等与支架血栓的发生关系密切(OR=9.765,95%CI为3.083～30.928;OR=5.243,95%CI为2.442～11.260;OR=1.014,95%CI为1.006～1.021).结论 PPIs可以明显减少PCI术后双联抗血小板治疗所致胃肠道出血的危险,使用PPIs时间长短对该保护作用无明显影响,既往胃肠复合疾病史可能是PCI术后发生胃肠道出血的独立高危因素.PPIs对PCI术后双联抗血小板治疗者可能性支架血栓的发生率无明显影响,肾功能不全、既往心肌梗死病史、血小板计数增高可能是其高危因素.     

Antireflux surgery in the proton pump inhibitor era

Although proton pump inhibitors (PPIs) are now the first-line treatment for gastroesophageal reflux disease (GERD), surgery still has several specific indications. We review the current treatment of GERD and discuss how antireflux surgery fits into the overall scheme.     

Gastric epithelial cell modality and proton pump inhibitor

Proton pump inhibitors (PPIs) are now commonly used for the treatment of acid related diseases such as peptic ulcer and reflux esophagitis. Because of their ability to produce direct inhibition of the proton pump, PPIs provide more sustained increase of the gastric pH than H(2)-receptor (H(2)R) antagonists. Diverse reports have been published on gastric epithelial cell modality associated with PPI treatment both in animal models and clinical settings. The present review summarizes the recent accumulated evidence on gastric epithelial cell modality associated with PPI treatment, including the formation of gastric carcinoid tumors and fundic gland polyps, and the development of gastric mucosal atrophy. Long-term PPI treatment has been reported to cause enlargement of the parietal cells and enterochromaffin-like cells, and to decrease the number of chief cells without affecting A-like cell. Although the development of gastric carcinoid tumors after chronic PPI treatment has been reported in animal studies, no such occurrences have been demonstrated in humans. The effect of PPIs on the formation of fundic gland polyps and the development of atrophic gastritis should be investigated in future studies.     

Discovery and development of the proton pump inhibitor]

Gastric (H+/K+)-ATPase, the proton pump of the parietal cell, is responsible for the final step of acid secretion in the stomach. In 1981, picoprazole, a substituted benzimidazole, was found to inhibit (H+/K+)-ATPase. It was reported in 1983 that omeprazole has the most potent efficacy among the substituted benzimidazoles and today, omeprazole has been used for treatment of gastroduodenal disease. Recently, lansoprazole, similar to omeprazole in chemical structure, was developed in Japan, and several other compounds, such as pantoprazole, E-3810 and NC-1300-O-3, have also been reported to suppress acid secretion through inhibition of (H+/K+)-ATPase. In the present paper the background of the discovery of (H+/K+)-ATPase and development of proton pump inhibitors is reviewed.     

术前使用质子泵抑制剂对胃部内镜黏膜下剥离术相关性出血作用的初步研究

目的探讨术前使用质子泵抑制剂对胃部内镜黏膜下剥离术相关性出血的预防作用。方法 148例患者按病灶大小(2 cm)随机分为术前用药组(n=76)和对照组(n=72)进行内镜黏膜下剥离术(ESD),术前用药组术前1 d口服泮托拉唑片40 mg,手术当天上午静滴泮托拉唑40 mg,下午行ESD,两组术后当天静滴泮托拉唑40 mg,第1至第3天早晚各静滴泮托拉唑40 mg,术后第4天改泮托拉唑口服40 mg/d,术后d1、d7、d28复查胃镜,并将溃疡进行Forrest分级,ESD术前、术后检测胃液pH值,并统计两组术中及术后延迟性出血的比例。结果术前用药组ESD时胃液pH值明显高于对照组(P<0.05),而术后无差异;两组均未出现术中大量出血,术中少量出血术前用药组1例,对照组10例(P<0.05);在术后迟发性出血术前用药组4例,对照组3例(P>0.05);术后第1天复查胃镜ForrestⅡa级溃疡术前用药组3例,对照组9例(P<0.05),ForrestⅡb级溃疡术前用药组5例,对照组14例(P<0.05)。结论术前使用质子泵抑制剂能减少胃部ESD术中出血,但并不能减少术后迟发性出血的发生。     

Appropriate choice of proton pump inhibitor therapy in the prevention and management of NSAID-related gastrointestinal damage

Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with gastrointestinal adverse effects, ranging from dyspepsia and peptic ulcer disease to more serious complications such as haemorrhage or perforation. NSAID-induced gastrointestinal toxicity is a significant medical problem worldwide. Misoprostol is effective in reducing NSAID-induced mucosal damage, but patient compliance is limited by poor tolerance. Histamine receptor antagonists are relatively effective against duodenal ulcers but offer no significant protection against gastric ulcers. Proton pump inhibitors (PPIs), such as pantoprazole, omeprazole and lansoprazole, have been shown to be effective in preventing the development of gastric and duodenal ulcers in high-risk patients taking NSAIDs. PPI therapy is also beneficial in healing NSAID-induced ulcers and preventing their recurrence in patients requiring ongoing NSAID therapy. PPIs have an excellent safety profile, and pantoprazole--with its low potential for drug-drug interactions--is particularly suitable for administration to elderly patients who often require concomitant treatment with other medications.     

血清不对称二甲基精氨酸与服用质子泵抑制剂后初次发生急性冠状动脉综合征的相关性

目的本研究旨在探讨血清不对称二甲基精氨酸（ADMA）与服用质子泵抑制剂（PPI）后初次发生急性冠状动脉综合征（ACS）的关系。 方法研究纳入2017年1月至2018年10月因初次发生ACS入住徐州医科大学附属淮安医院的患者及体检中心同期健康体检者共210例,分为3组,PPI组（服用PPI＋初次发生ACS）患者70例,其中男性51例,女性19例,平均年龄为（62.80±11.87）岁;ACS组（未服用PPI＋初次发生ACS）患者70例,其中男性55例,女性15例,平均年龄为（62.66±12.13）岁;对照组为同期健康体检患者（未服用PPI＋未发生ACS）70人,其中男性54人,女性16人,平均年龄为（62.96±9.09）岁。采用酶联免疫吸附法检测血清ADMA浓度,同时测量总胆固醇、三酰甘油等指标。采用单因素方差分析、非参数检验和χ²检验比较3组研究对象一般人口学信息、各项生化指标及ADMA水平;组间两两比较采用Mann-Whitney U检验;采用Spearman相关分析分析血清ADMA水平与ACS传统危险因素的关系;采用多因素Logistic回归分析探讨ACS的独立危险因素。 结果PPI组和ACS组的血清ADMA水平均高于对照组,差异均有统计学意义（Z=-9.585、-4.793,P均<0.001）;PPI组的血清ADMA水平高于ACS组,差异具有统计学意义（Z=-8.750,P<0.001）;PPI组和ACS组（即ACS患者）的血清ADMA水平与年龄、性别、BMI、吸烟、糖尿病、高血压、总胆固醇、三酰甘油无相关性（P均>0.05）;Logistic回归分析显示血清ADMA水平是初发ACS患者的独立危险因素（β=0.017,OR=1.017,P<0.001）。 结论服用PPI后初次发生ACS患者的血清ADMA水平明显高于未服用PPI的初次发生ACS患者;初次发生ACS患者的血清ADMA水平明显高于健康对照者;血清ADMA升高是初次发生ACS的独立危险因素。