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Background: Multiple Helicobacter pylori second-line schedules have been described as potentially useful. It remains unclear, however, which are the best combinations, and which features of second-line treatments are related to better cure rates. The aim of this study was to determine that second-line treatments achieved excellent (>90%) cure rates by performing a systematic review and when possible a meta-analysis. A meta-regression was planned to determine the characteristics of treatments achieving excellent cure rates., Methods: A systematic review for studies evaluating second-line Helicobacter pylori treatment was carried out in multiple databases. A formal meta-analysis was performed when an adequate number of comparative studies was found, using RevMan5.3. A meta-regression for evaluating factors predicting cure rates >90% was performed using Stata Statistical Software., Results: The systematic review identified 115 eligible studies, including 203 evaluable treatment arms. The results were extremely heterogeneous, with 61 treatment arms (30%) achieving optimal (>90%) cure rates. The meta-analysis favored quadruple therapies over triple (83.2% vs 76.1%, OR: 0.59:0.38-0.93; P = .02) and 14-day quadruple treatments over 7-day treatments (91.2% vs 81.5%, OR; 95% CI: 0.42:0.24-0.73; P = .002), although the differences were significant only in the per-protocol analysis. The meta-regression did not find any particular characteristics of the studies to be associated with excellent cure rates., Conclusion: Second-line Helicobacter pylori treatments achieving>90% cure rates are extremely heterogeneous. Quadruple therapy and 14-day treatments seem better than triple therapies and 7-day ones. No single characteristic of the treatments was related to excellent cure rates. Future approaches suitable for infectious diseases-thus considering antibiotic resistances-are needed to design rescue treatments that consistently achieve excellent cure rates., (© 2018 John Wiley & Sons Ltd.)

Introduction: The efficacy of currently recommended third-line therapies for Helicobacter pylori is suboptimal, even that of culture-guided treatments. Resistance to multiple antibiotics is the major factor related to treatment failure. The aim of this study was to evaluate the effectiveness and safety of a 14-day therapy using high-dose of amoxicillin, metronidazole and esomeprazole., Material and Methods: Multicenter open-label study as a register in routine clinical practice in patients with two previous failures of eradication therapy. A triple therapy with esomeprazole 40 mg b.d., amoxicillin 1 g t.d.s and metronidazole 500 mg t.d.s for 2 weeks was administered as a third-line therapy after a first treatment including clarithromycin and a second treatment including a quinolone. Helicobacter pylori status was determined by either histology or 13 C-UBT both before and after treatment., Results: A total of 68 patients were included in this study. An interim analysis showed that only three out of eight patients who had received metronidazole in previous eradication regimens were cured (37%, 95% CI 8-75); as a result, after this interim analysis only metronidazole-naïve patients were included. The ITT eradication rate in metronidazole-naive patients was 64% (95% CI 51-76). Adverse events occurred in 58% of patients, all of them mild-to-moderate. Two patients (3%) did not complete >90% of the treatment because of side effects. No severe adverse events occurred., Conclusion: Cure rates of this 14-day schedule using high-dose esomeprazole, amoxicillin and metronidazole as a third-line eradication regimen were suboptimal, especially in patients who had received metronidazole in previous failed eradication regimens., (© 2017 John Wiley & Sons Ltd.)

Background: Due to clarithromycin resistance, the current efficacy of Helicobacter pylori first-line triple therapies including clarithromycin is low. It seems reasonable to explore alternative clarithromycin-free therapies., Objectives: The objective of this study was to evaluate the efficacy of triple therapy including a proton-pump inhibitor (PPI), amoxicillin and metronidazole (PAM) as first-line H. pylori therapy by systematic review and meta-analysis., Methods: Studies evaluating PAM in adult patients were included. Meta-analyses comparing PAM with other treatments were performed. The primary endpoint was the ITT eradication rate for H. pylori first-line treatment. In addition, sensitivity analyses ascertained the effects of treatment schedule, dosage and duration on cure rates., Results: Ninety-four studies (8061 patients) were included. Meta-analyses comparing PAM versus clarithromycin-including triple therapies showed a significant difference in favour of PPI, amoxicillin and clarithromycin (PAC) (70% versus 77.1%; OR = 0.70, 95% CI = 0.56-0.88) and PPI, metronidazole and clarithromycin (PMC) therapy (66.4% versus 77.7%; OR = 0.55, 95% CI = 0.39-0.76). Sensitivity analyses showed a similar efficacy of PAM versus PAC when drugs were administered for 14 days (80% versus 84%; OR = 0.70, 95% CI = 0.44-1.12). There were not enough studies to perform further comparisons. Number of antibiotic doses (P = 0.012), length of treatment (P < 0.001) and use of high metronidazole doses (P = 0.021) were related to higher cure rates in the sensitivity analysis including observational studies., Conclusions: PAM was less efficacious than clarithromycin-including triple therapies. However, its efficacy was similar to that of PAC when drugs were administered for 14 days, although ITT cure rates did not reach 90%. Use of 14 day, thrice daily and high-metronidazole-dose PAM treatments markedly increased the cure rate., (© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Proton pump inhibitors (PPI) are a major cause of false-negative Helicobacter pylori test results. Detecting PPI use and stopping it 2 weeks before testing is the preferred approach to improve the reliability of H pylori diagnostic tests. Immunoblot and molecular methods may be useful for the detection of H pylori infection in difficult cases. When conventional tests are negative and eradication is strongly indicated, empirical H pylori treatment should be considered. In this article, an updated critical review of the usefulness of the various invasive and noninvasive tests in the context of extensive PPI use is provided., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To assess rates of further bleeding, surgery and mortality in patients hospitalized owing to peptic ulcer bleeding., Materials and Methods: Consecutive patients hospitalized for peptic ulcer bleeding and treated with a proton pump inhibitor (PPI) (esomeprazole or pantoprazole) were identified retrospectively in 12 centers in Spain. Patients were included if they had high-risk stigmata (Forrest class Ia-IIb, underwent therapeutic endoscopy and received intravenous PPI ≥120 mg/day for ≥24 h) or low-risk stigmata (Forrest class IIc-III, underwent no therapeutic endoscopy and received intravenous or oral PPI [any dose])., Results: Of 935 identified patients, 58.3% had high-risk stigmata and 41.7% had low-risk stigmata. After endoscopy, 88.3% of high-risk patients and 22.1% of low-risk patients received intravenous PPI therapy at doses of at least 160 mg/day. Further bleeding within 72 h occurred in 9.4% and 2.1% of high- and low-risk patients, respectively (p < 0.001). Surgery to stop bleeding was required within 30 days in 3.5% and 0.8% of high- and low-risk patients, respectively (p = 0.007). Mortality at 30 days was similar in both groups (3.3% in high-risk and 2.3% in low-risk patients)., Conclusion: Among patients hospitalized owing to peptic ulcer bleeding and treated with PPIs, patients with high-risk stigmata have a higher risk of further bleeding and surgery, but not of death, than those with low-risk stigmata.

Background: The optimal duration for Helicobacter pylori (H. pylori) eradication therapy is controversial, with recommendations ranging from 7 to 14 days. Several systematic reviews have attempted to address this issue but have given conflicting results and limited their analysis to proton pump inhibitor (PPI), two antibiotics (PPI triple) therapy. We performed a systematic review and meta-analysis to investigate the optimal duration of multiple H. pylori eradication regimens., Objectives: The primary objective was to assess the relative effectiveness of different durations (7, 10 or 14 days) of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events., Search Methods: The Cochrane Library, MEDLINE, EMBASE, and CINAHL were searched up to December 2011 to identify eligible randomised controlled trials (RCTs). We also searched the proceedings of six conferences from 1995 to 2011, dissertations and theses, and grey literature. There were no language restrictions applied to any search., Selection Criteria: Only parallel group RCTs assessing the efficacy of one to two weeks duration of first line H. pylori eradication regimens in adults were eligible. Within each regimen, the same combinations of drugs at the same dose were compared over different durations. Studies with at least two arms comparing 7, 10, or 14 days were eligible. Enrolled participants needed to be diagnosed with at least one positive test for H. pylori on the basis of a rapid urease test (RUT), histology, culture, urea breath test (UBT), or a stool antigen test (HpSA) before treatment. Eligible trials needed to confirm eradication of H. pylori as their primary outcome at least 28 days after completion of eradication treatment. Trials using only serology or a polymerase chain reaction (PCR) to determine H. pylori infection or eradication were excluded., Data Collection and Analysis: Study eligibility and data extraction were performed by two independent review authors. Data analyses were performed within each type of intervention, for both primary and secondary outcomes. The relative risk (RR) and number needed to treat (NNT)/number needed to harm (NNTH) according to duration of therapy were calculated using the outcomes of H. pylori persistence and adverse events. A random-effects model was used. Subgroup analyses and sensitivity analyses were planned a priori., Main Results: In total, 75 studies met the inclusion criteria. Eight types of regimens were reported with at least two comparative eligible durations. They included: PPI + two antibiotics triple therapy (n = 59), PPI bismuth-based quadruple therapy (n = 6), PPI + three antibiotics quadruple therapy (n = 1), PPI dual therapy (n = 2), histamine H2-receptor antagonist (H₂RA) bismuth quadruple therapy (n = 3), H₂RA bismuth-based triple therapy (n = 2), H₂RA + two antibiotics triple therapy (n = 3), and bismuth + two antibiotics triple therapy (n = 2). Some studies provided data for more than one regimen or more than two durations.For the PPI triple therapy, 59 studies with five regimens were reported: PPI + clarithromycin + amoxicillin (PCA); PPI + clarithromycin + a nitroimidazole (PCN); PPI + amoxicillin + nitroimidazole (PAN); PPI + amoxicillin + a quinolone (PAQ); and PPI + amoxicillin + a nitrofuran (PANi). Regardless of type and dose of antibiotics, increased duration of PPI triple therapy from 7 to 14 days significantly increased the H. pylori eradication rate (45 studies, 72.9% versus 81.9%), the RR for H. pylori persistence was 0.66 (95% CI 0.60 to 0.74), NNT was 11 (95% CI 9 to 14). Significant effects were seen in the subgroup of PCA (34 studies, RR 0.65, 95% CI 0.57 to 0.75; NNT 12, 95% CI 9 to 16); PAN (10 studies, RR 0.67, 95% CI 0.52 to 0.86; NNT = 11, 95% CI 8 to 25); and in PAQ (2 studies, RR 0.37, 95% CI 0.16 to 0.83; NNT 3, 95% CI 2 to 10); but not in PCN triple therapy (4 studies, RR 0.87, 95% CI 0.71 to 1.07). Significantly increased eradication rates were also seen for PPI triple therapy with 10 versus 7 days (24 studies, 79.9% versus 75.7%; RR 0.80, 95% CI 0.72 to 0.89; NNT 21, 95% CI 15 to 38) and 14 versus 10 days (12 studies, 84.4% versus 78.5%; RR 0.72, 95% CI 0.58 to 0.90; NNT 17, 95% CI 11 to 46); especially in the subgroup of PAC for 10 versus 7 days (17 studies, RR 0.80, 95% CI 0.70 to 0.91) and for 14 versus 10 days (10 studies, RR 0.69, 95% CI 0.52 to 0.91). A trend towards increased H. pylori eradication rates was seen with increased duration of PCN for 10 versus 7 days, and of PAN for 10 versus 7 days and 14 versus 10 days, though this was not statistical significant. The proportion of patients with adverse events, defined by authors, was marginally significantly increased only between 7 days and 14 days (15.5% versus 19.4%; RR 1.21, 95% CI 1.06 to 1.37; NNTH 31, 95% CI 18 to 104) but not for other duration comparisons. The proportion of patients discontinuing treatment due to adverse events was not significantly different between treatment durations.Only limited data were reported for different durations of regimens other than PPI triple therapy. No significant difference of the eradication rate was seen for all regimens according to different durations except for H₂RA bismuth quadruple therapy, where a significantly higher eradication rate was seen for 14 days versus 7 days, however only one study reported outcome data., Authors' Conclusions: Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy; more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.

Objective: To assess clinical outcomes in patients treated with proton pump inhibitors (PPIs) after endoscopic hemostasis in routine clinical care, and to compare these outcomes to those seen in a randomized controlled trial (RCT) of i.v. esomeprazole., Materials and Methods: Patients with peptic ulcer bleeding and endoscopic stigmata of recent hemorrhage, who were treated with i.v. esomeprazole or pantoprazole ≥120 mg/day following therapeutic endoscopy, were identified from 12 hospitals in Spain (n = 539). Outcomes assessed included further bleeding, all-cause mortality and surgery. The results were compared to those of the RCT., Results: Overall, 9.1% (95% confidence interval [CI]: 6.7-11.5) of patients experienced further bleeding within 72 h following initial endoscopy, 14.3% (95% CI: 11.3-17.2) of patients had further bleeding within 30 days and 3.3% (95% CI: 1.8-4.9) of patients died within 30 days. In the RCT, the rate of rebleeding within 72 h was significantly lower in the esomeprazole arm (5.9%) than in the placebo arm (10.3%; p = 0.026). The further bleeding rate in patients treated with esomeprazole in routine clinical practice (7.8%; 95% CI: 4.6-11.1) was between these two values. Similar results were seen with the other outcomes studied., Conclusions: The proportion of patients treated with i.v. esomeprazole in routine clinical practice who experienced further bleeding following endoscopic treatment for peptic ulcer bleeding was between the rates observed in the esomeprazole group and the placebo group in the RCT.

Background: The decreasing efficacy of H. pylori eradication treatments over time makes the search for better regimens and adjuvant medications a priority., Aim: To conduct a meta-analysis of studies comparing rabeprazole or esomeprazole with other proton pump inhibitors (PPI) or with each other in H. pylori eradication treatment., Selection of Studies: Randomised clinical trials comparing esomeprazole or rabeprazole with first-generation PPIs (omeprazole-lansoprazole-pantoprazole) or with each other., Results: The meta-analysis (35 studies, 5998 patients) showed higher eradication rates for esomeprazole than for first-generation PPIs: 82.3% vs. 77.6%; OR = 1.32(1.01-1.73); NNT = 21. Rabeprazole also showed better results than first-generation PPIs: 80.5% vs. 76.2%; OR = 1.21(1.02-1.42); NNT = 23. PPI dosage sub-analysis: only esomeprazole 40 mg b.d. improved results [83.5% esomeprazole vs. 72.4% first generation; OR = 2.27(1.07-4.82); NNT = 9]. Whereas rabeprazole 10 and 20 mg b.d. maintained results, esomeprazole 20 mg b.d. obtained lower efficacy. Esomeprazole vs. rabeprazole sub-analysis (five studies): no significant differences were found: 78.7% vs. 76.7%; OR = 0.90(0.70-1.17). CYP2C19 sub-analysis: Genotype did not significantly affect eradication either in first [OR = 1.76(0.99-3.12)] or new generation [OR = 1.19(0.73-1.95)] PPIs. However, sub-analysis considering only extensive metaboliser patients showed higher eradication with new-generation PPIs [OR = 1.37(1.02-1.84)]., Conclusions: Esomeprazole and rabeprazole show better overall H. pylori eradication rates than first-generation PPIs. This clinical benefit is more pronounced in esomeprazole 40 mg b.d. regimens. In CYP2C19 extensive metabolisers, new-generation PPIs are more effective than first-generation PPIs for H. pylori eradication. However, a general recommendation of using new-generation PPIs in all scenarios remains unclear., (© 2012 Blackwell Publishing Ltd.)

H2-receptor antagonists (H2RA) and proton pump inhibitors (PPI) are widely used for aspiration prophylaxis in patients receiving general anaesthesia. Many randomized trials have compared these agents but it remains unclear which drug type is more effective in reducing the number of patients at risk of complications. The study aimed to compare their efficacy for decreasing the number of patients at risk of acid aspiration during general anaesthesia. Major databases were systematically searched. Randomized controlled trials comparing PPI and H2RA were selected. Sub-analyses were performed considering the dose, the dosing schedule, and the route of administration. Eighteen studies fulfilled the inclusion criteria. The main analysis showed a non-significant trend for H2RA being more effective than PPI. Only when both drugs were administered per os, as a single dose and immediately before surgery, was H2RA significantly more effective than PPI. By contrast, the effect of PPI and H2RA was similar when they were administered in two doses (the night before and on the morning of surgery) or when the drugs were given intravenously. A single H2RA dose before surgery is highly effective in reducing the number of patients at risk of acid aspiration. PPI administered in two oral doses or in a single intravenous infusion seems to be as effective as H2RA., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

BACKGROUND  A decrease in the Helicobacter pylori eradication rate after standard triple therapy has been suggested in recent years. AIM  To assess the efficacy of standard triple therapy in the eradication of H. pylori through an epidemiological analysis of all published Spanish trials. A secondary aim was to review the prevalence of clarithromycin resistance in Spain. METHODS  Articles on H. pylori eradication in Spain published in peer-reviewed journals were identified through MEDLINE searches. Studies that included a triple therapy consisting of any proton pump inhibitor with clarithromycin (500 mg b.d.) and amoxicillin (1 g b.d.) for up to 14 days were selected. Spanish studies evaluating the prevalence of clarithromycin resistance were also reviewed. Meta-analysis was performed using the generic inverse variance method. RESULTS The pooled eradication rates by year from Spanish studies evaluating the efficacy of the standard triple regimen revealed a relatively constant rate over the years. Overall, the analysis of the 32 studies (4727 patients) showed a mean H. pylori cure rate of 80% (95% CI = 77-82%) by intention-to-treat and 83% (81-86%) by per-protocol. When only peptic ulcer disease or 7-day regimens were considered, results were similar. Based on 13 studies (3293 patients), mean clarithromycin resistance rate was 8% (5-10%). CONCLUSION Although a decrease in the H. pylori eradication rate after triple therapy has been suggested in recent years, cure rates with this regimen did not change in Spain between 1997 and 2008. However, this by no means indicates that the efficacy of standard triple therapy in Spain is acceptable, as it has been calculated to be around only 80%. Therefore, it is evident that new strategies to improve first-line treatment are urgently needed., (© 2011 Blackwell Publishing Ltd.)

Background: Traditional standard triple therapy for Helicobacter pylori infection (PPI-clarithromycin-amoxicillin) can easily be converted to non-bismuth quadruple (concomitant) therapy by the addition of a nitroimidazole twice daily., Aim: To critically review evidence on the role of non-bismuth quadruple therapy (PPI-clarithromycin-amoxicillin-nitroimidazole) in the treatment of H. pylori infection., Methods: Bibliographical searches were performed in MEDLINE and relevant congresses., Results: The first randomised comparison of the non-bismuth quadruple therapy and the sequential (PPI-amoxicillin 5days plus PPI-clarithromycin-nitroimidazole 5days) regimens recently concluded that both were similar in terms of efficacy and safety and that the sequential administration protocol may be unnecessarily complex. Several randomised controlled trials (and one meta-analysis) have demonstrated that non-bismuth quadruple therapy is more effective than and is equally well tolerated as standard triple therapy. A meta-analysis of 15 studies (1723 patients) revealed a mean H. pylori cure rate (intention-to-treat) of 90% for non-bismuth quadruple therapy. A tendency towards better results with longer treatments (7-10days vs. 3-5days) has been observed, so it seems reasonable to recommend the length of treatment by achieving maximal cure rates (10days). Clarithromycin resistance may reduce the efficacy of non-bismuth quadruple therapy, although the decrease in eradication rates seems to be far lower than in standard triple therapy. Experience with the non-bismuth quadruple therapy in patients with metronidazole-resistant strains is still very limited., Conclusions: Non-bismuth quadruple (concomitant) therapy appears to be an effective, safe, and well-tolerated alternative to triple therapy and is less complex than sequential therapy. Therefore, this regimen appears well suited for use in settings where the efficacy of triple therapy is unacceptably low., (© 2011 Blackwell Publishing Ltd.)

Gastric pH should be maintained at very high values to prevent peptic ulcer rebleeding. A recent randomized trial, however, has confirmed that intravenous infusion of esomeprazole decreases the rebleeding rate after endoscopic therapy. In addition, the use of proton pump inhibitor perfusion at admission before diagnostic endoscopy reduces the need for endoscopic therapy and shortens the mean length of hospital stay., (Copyright 2010 Elsevier España S.L. All rights reserved.)

Importance of the Field: Standard triple therapy (STT) is the most used treatment for Helicobater pylori infection. The prevalence of antibiotic resistance has increased substantially in recent years and there has been a corresponding decrease in efficacy., Areas Covered in This Review: Bibliographical searches were performed in MEDLINE and international congresses up to 2009 for 'Helicobacter pylori' AND 'sequential regimen/therapy'., What the Reader Will Gain: Several meta-analyses have demonstrated that sequential therapy (SQT) is more effective than STT. SQT is not affected by bacterial and host factors that have, until now, predicted the outcome of STT. Primary clarithromycin resistance is the only factor reducing the efficacy of SQT; however, even in these patients an acceptable > 75% eradication can be achieved. So far, almost all the studies have been performed in Italy. The advantages of SQT over STT should be confirmed in different countries. Whether it is necessary to provide the drugs sequentially or if the four components of SQT can be given concurrently is unclear., Take Home Message: SQT is a promising new treatment approach that deserves consideration as a treatment strategy for H. pylori infection. However, further robust assessment across a much broader range of patients is required before SQT could supplant existing treatment regimens and be generally recommended in clinical practice.

Background: The evidence on whether high-dose proton pump inhibitors (PPIs) increase cure rates of Helicobacter pylori treatment has not been previously assessed., Aim: To evaluate the evidence on the usefulness of high-dose PPI in standard triple therapy by performing a systematic review and a meta-analysis., Methods: A systematic search was performed in multiple databases and in the abstracts submitted to the Digestive Diseases Week, the European Helicobacter Study Group congress and the United European Gastroenterology Week. Randomized trials comparing a standard dose of a PPI with high-dose PPI both twice a day in triple therapy combining a PPI plus clarithromycin and either amoxicillin or metronidazole were selected. Relative risk (RR) and 95% confidence intervals (95% CIs) for all comparisons were calculated using Review Manager., Results: Six studies fulfilled the inclusion criteria. All used triple therapy for 7 days. A mean intention-to-treat cure rate of 82% was achieved with high-dose PPI and one of 74% with standard dose (RR: 1.09; 95% CI: 1.01-1.17). Subgroup analysis showed that the maximum increase was observed when the PPI compared were omeprazole 20 mg or pantoprazole 40 mg vs. esomeprazole 40 mg., Conclusion: High-dose PPI seems more effective than standard-dose for curing H. pylori infection in 7-day triple therapy.

Background: Cure rates of Helicobacter pylori infection with standard triple therapy are disappointingly low. A very effective, new sequential treatment schedule has recently been described. However, all studies published to date were performed in Italy; it is mandatory to confirm these results in other settings., Aim: To assess the cure rate and the acceptability of a new sequential treatment regimen through a pilot study., Methods: A hundred and thirty-nine patients (60% men, mean age 49.6 +/- 15.7 yr) were recruited from six centers. H. pylori status was assessed by histology, urease test or urea breath test. Sequential regime consisted of a 10-day treatment including a proton pump inhibitor (PPI) b.d. plus amoxicillin 1 g b.d. for the first 5 days, followed by a PPI b.d. clarithromycin 500 mg b.d. and metronidazole 500 mg b.d for the next 5 days. Eradication was determined 8 wk after the end of treatment by urea breath test or histology. Eradication rates were calculated both per protocol and by intention-to-treat., Results: Eradication was achieved in 117 out of 129 patients who returned for a follow-up test. The intention-to-treat eradication rate was thus 84.2% (95%CI: 77%-90%) and the per-protocol cure rate 90.7% (95%CI: 84%-95%). The treatment was well tolerated. Only 14 patients complained of mild side effects., Conclusions: Sequential treatment seems highly effective for eradicating H. pylori.

Background: Ten-day triple therapy is somewhat more effective than 7-day treatment for curing Helicobacter pylori infection. Recent studies have suggested that rabeprazole-a proton pump inhibitor with fast onset of acid inhibition-could raise the efficacy of 7-day therapies to the levels obtained with 10-day treatment., Objective: To compare the efficacy of 7- and 10-day rabeprazole-based triple therapy for H. pylori eradication., Patients and Methods: Four hundred and fifty-eight patients were randomized to 7 or 10 days of triple therapy, including rabeprazole 20 mg, clarithromycin 500 mg, and amoxicillin 1 g, all twice a day. Cure rates were evaluated by urea breath test., Results: Two hundred and thirty-seven patients received 7-day and 221 received 10-day therapy. Groups were comparable in terms of demographic variables. Intention to treat cure rates were 73.8% (95% CI: 67-79%) for 7-day and 79.6% (95%: CI:74-85%) for 10-day therapy (p= 0.09). Per-protocol cure rates were 81.8% (95% CI:76-86%) and 89.3% (95% CI: 84-93%), p= 0.02, respectively. Cure rates were similar in peptic ulcer patients but in subjects without ulcer they were clearly lower for 7-day therapy: 66%versus 77% by intention to treat (p= 0.08) and 73%versus 91% in the per-protocol analysis (p= 0.004). Side effects and compliance in the two groups were comparable., Conclusions: Seven- and 10-day triple therapies seem equally efficient in peptic ulcer patients. In contrast, 7-day therapy is significantly less effective in nonulcer dyspepsia patients. Ten-day therapy, therefore, seems preferable when treating nonulcer patients.

Objective: To systematically review the Helicobacter pylori eradication efficacy with ranitidine bismuth citrate (RBC) and two antibiotics, and to conduct a meta-analysis of randomized clinical trials comparing the efficacy of proton pump inhibitor (PPI) vs. RBC with two antibiotics for 1 week., Selection of Studies: Studies evaluating RBC plus two antibiotics were considered. For the meta-analysis, randomized controlled trials comparing PPI vs. RBC plus two antibiotics for 1 week were included., Search Strategy: Electronic and manual bibliographical searches. Assessment of study quality and data extraction: Independently done by two reviewers., Data Synthesis: 'Intention-to-treat' eradication rate. Meta-analysis was performed, combining the odds ratios (OR) of the individual studies. Subanalysis: Depending on the type of antibiotics and the quality of the studies., Results: Mean H. pylori eradication with 7-day RBC-clarithromycin-amoxicillin, RBC-clarithromycin-nitroimidazole, and RBC-amoxicillin-nitroimidazole was 83%, 86%, and 71%, respectively. The meta-analysis showed comparable efficacy with RBC and PPI when they were combined with clarithromycin and amoxicillin (OR = 1.11; 95% CI = 0.88-1.40), or with amoxicillin and metronidazole (OR = 0.92; 95%CI = 0.60-1.41). However, when comparing PPI vs. RBC plus clarithromycin and a nitroimidazole, higher cure rates with RBC than with PPI were demonstrated (OR = 1.65; 95% CI = 1.15-2.37)., Conclusion: The efficacy of RBC and PPI-based triple regimens were comparable when using the clarithromycin-amoxicillin or the amoxicillin-metronidazole combination. However, RBC seems to have a higher efficacy than PPI when clarithromycin and a nitroimidazole are the antibiotics prescribed. Therefore, if one prefers to use the clarithromycin-nitroimidazole regimen, RBC should be used instead of a PPI.

The clinical response to antisecretory treatment correlates directly with the degree of inhibition of acid secretion achieved. Acid inhibition able to maintain the intragastric pH at a value greater than 4 for at least 16 h/day seems to heal even the most refractory acid-related diseases. It has also been shown that the degree of inhibition of acid secretion in response to antisecretory treatment depends on the genetic characteristics of the patient and on the presence of Helicobacter pylori infection. A possible definition of potent (or profound) acid inhibition is, therefore, the achievement of the aforementioned level of control of acid secretion regardless of patient characteristics or of the presence of H. pylori infection. Antisecretory drugs differ in their ability to reach potent acid inhibition. As far as the comparative efficacy of different drugs for inhibiting acid secretion is concerned, proton pump inhibitors are more efficient in inhibiting gastric acid secretion than histamine (H2) receptor antagonists. Among the different proton pump inhibitors, esomeprazole 40 mg/day exhibits greater antisecretory potency than the others at standard doses. Rabeprazole 20 mg/day and lansoprazole 30 mg/day exhibit a more rapid onset of action than omeprazole 20 mg/day or pantoprazole 40 mg/day.

Acid inhibition is safe and useful in several clinical settings. Proton pump inhibitors are more effective than H2-receptor antagonists in virtually all cases. Proton pump inhibitors should be used in: the eradication of Helicobacter pylori; the treatment of non-H. pylori-related peptic ulcer healing; for the prevention and treatment of non-steroidal anti-inflammatory drug-induced upper digestive lesions; for bleeding peptic lesions; and, especially, in the short-term and long-term control of gastro-oesophageal reflux disease. The timing, the dosing and the specific drugs should be adapted to the particular patient, clinical situation and local factors. For instance, in a patient with active bleeding from a duodenal ulcer, intravenous constant infusion should be the preferred treatment. When seeking oral 'potent' acid inhibition (refractory gastro-oesophageal reflux disease, and perhaps Barrett's oesophagus), available data suggest that the pharmacological and clinical profiles of esomeprazole are slightly better.

Background: It is unknown whether proton pump inhibitors are superior to H2-receptor antagonists in Helicobacter pylori eradication regimens., Aim: To perform a meta-analysis comparing the efficacy of both antisecretors when co-prescribed with antibiotics., Methods: Randomized clinical trials comparing proton pump inhibitors vs. H2-receptor antagonists with the same antibiotics were selected. Data sources included PubMed, the Cochrane Controlled Trials Register and abstracts from congresses up to January 2002. A meta-analysis was performed by combining the odds ratios., Results: Twenty studies fulfilled the inclusion criteria. In the intention-to-treat analysis, the mean eradication rates with proton pump inhibitors and H2-receptor antagonists plus antibiotics were 74% [95% confidence interval (CI), 71-76%] and 69% (95% CI, 66-71%), respectively. The odds ratio for this comparison was 1.31 (95% CI, 1.09-1.58). The number needed to treat with proton pump inhibitors to achieve eradication success, compared with H2-receptor antagonists, was 25. When studies prescribing very high doses of H2-receptor antagonists (two of the outliers) were excluded, the odds ratio (for proton pump inhibitors vs. H2-receptor antagonists) increased to 1.37, the number needed to treat decreased to 20 and the heterogeneity between the studies decreased., Conclusions: Overall, proton pump inhibitors are more effective than H2-receptor antagonists when prescribed at usual doses with antibiotics to eradicate H. pylori infection.

Background: It is not known whether certain proton-pump inhibitors are more efficacious than others when used in triple therapy for Helicobacter pylori eradication., Aim: To compare the efficacy of different proton-pump inhibitors in triple therapy by performing a meta-analysis., Methods: A MEDLINE search was performed. Abstracts of the European Helicobacter pylori Study Group and the American Gastroenterological Association congresses from 1996 to 2002 were also examined. Randomized studies with at least two branches of triple therapy that differed only in terms of type of proton-pump inhibitor were included in a meta-analysis using Review Manager 4.1., Results: Fourteen studies were included. Intention-to-treat cure rates were similar for omeprazole and lansoprazole: 74.7% vs. 76%, odds ratio (OR) 0.91 [95% confidence interval (CI) 0.69-1.21] in a total of 1085 patients; for omeprazole and rabeprazole: 77.9% vs. 81.2%, OR 0.81 (95% CI 0.58-1.15) in a total of 825 patients; for omeprazole and esomeprazole: 87.7% vs. 89%, OR 0.89 (95% CI 0.58-1.35) in 833 patients; and for lansoprazole and rabeprazole: 81% vs. 85.7%, OR 0.77 (95% CI 0.48-1.22) in 550 patients., Conclusion: The efficacy of various proton-pump inhibitors seems to be similar when used for H. pylori eradication in standard triple therapy.

Background: Triple therapies combining a double dose of proton pump inhibitor plus two antibiotics are the standard treatment for Helicobacter pylori infection. Some reports suggest that the use of half the dose of proton pump inhibitor is equally effective., Aim: To compare the efficacy of a single vs. double dose of proton pump inhibitor in triple therapy., Methods: We conducted a MEDLINE search. The search strategy included the words (pylori) AND (triple, PPI, proton pump, omeprazole, rabeprazole, pantoprazole, lansoprazole, clarithromycin, amoxicillin, amoxycillin or metronidazole). Abstracts of the articles obtained and papers presented at the European Helicobacter pylori Study Group and American Gastroenterological Association congresses from 1996 to 2001 were examined. Inclusion criteria were: (i) randomized studies with at least two branches of triple therapy including a proton pump inhibitor and two standard antibiotics; (ii) branches could differ only in terms of proton pump inhibitor dosage. A meta-analysis was conducted using conventional shareware (Review Manager 4.1)., Results: Thirteen studies met the inclusion criteria with a total of 2391 patients. Cure rates with double doses of proton pump inhibitor were higher in both the intention-to-treat analysis (83.9% vs. 77.7%; Peto odds ratio, 1.51; 95% confidence interval, 1.23-1.85; P < 0.01) and per protocol analysis (89% vs. 81%; Peto odds ratio, 1.96; 95% confidence interval, 1.55-2.47; P < 0.01)., Conclusion: Triple therapies containing a single dose of proton pump inhibitor are less effective than those containing a standard double dose of proton pump inhibitor.

Purpose: To evaluate whether proton pump inhibitors are more effective than H2-antagonists (H2-A) for the treatment of bleeding peptic ulcer., Data Sources: PubMed database until January 2000., Study Selection: Comparative randomized trials of proton pump inhibitors (omeprazole, lansoprazole, or pantoprazole) vs. H2-A (cimetidine, ranitidine or famotidine)., Data Extraction: Meta-analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method). OUTCOMES EVALUATED: Persistent or recurrent bleeding, need for surgery, or mortality., Data Synthesis: Eleven studies fulfilled the inclusion criteria and contained data for at least one of the planned comparisons. Persistent or recurrent bleeding was reported in 6.7% (95% CI: 4.9-8.6%) of the patients treated with proton pump inhibitors, and in 13.4% (95% CI: 10.8-16%) of those treated with H2-A (OR 0.4; 95% CI: 0.27-0.59) (chi2-homogeneity test, 18; P=0.09). Surgery was needed in 5.2% (95% CI: 3.4-6.9%) of the patients treated with proton pump inhibitors, and in 6.9% (95% CI: 4.9-8.9%) of the patients treated with H2-A (OR 0.7; 95% CI: 0.43-1.13). Respective percentages for mortality were 1.6% (95% CI: 0.9-2.9%) and 2.2% (95% CI: 1.3-3.7%) (OR 0.69; 95% CI: 0.31-1.57). SUB-ANALYSIS: Five studies evaluated the effect of both therapies given in bolus injections on persistent or recurrent bleeding rate, which was 6% (95% CI: 3.6-8.3%) and 8.1% (95% CI: 5.3-10.9%), respectively (OR, 0.57; 95% CI: 0.31-1.05). Persistent or recurrent bleeding in high risk patients (Forrest Ia, Ib and IIa) occurred in 13.2% (95% CI: 7.9-8%) of the patients treated with proton pump inhibitors and in 34.5% (27-42%) of those treated with H2-A (OR 0.28; 95% CI: 0.16-0.48). In patients not having endoscopic therapy, persistent or recurrent bleeding was reported, respectively, in 4.3% (95% CI: 2.7-6.7%) and in 12% (95% CI: 8.7-15%) (OR 0.24; 95% CI: 0.13-0.43). Less marked differences were observed in patients having adjunct endoscopic therapy: 10.3% (95% CI: 6.7-13.8%) and 15.2% (11.1-19.3%) (OR 0.59; 95% CI: 0.36-0.97). Moreover, the significance disappeared in this group when a single outlier study was excluded., Conclusions: Proton pump inhibitors are more effective than H2-A in preventing persistent or recurrent bleeding from peptic ulcer, although this advantage seems to be more evident in patients not having adjunct sclerosis therapy. This beneficial effect seems to be similar or even more marked in patients with Forrest Ia, Ib or IIa ulcers. However, proton pump inhibitors are not more effective than H2-A for reducing surgery or mortality rates. Nevertheless, the data are too scarce and heterogeneous to draw definitive conclusions, and further comparative trials are clearly warranted.

Background: Triple therapy with a proton pump inhibitor, clarithromycin and amoxicillin is widely used for H. pylori infection. The appropriate length of treatment remains controversial., Aim: To determine whether length of treatment has an impact on the cost-effectiveness of triple therapy., Methods: The study took the form of a cost-effectiveness analysis spanning 2 years. The perspective was societal and the setting, ambulatory care. Subjects were Helicobacter pylori-positive patients with a duodenal ulcer. The triple therapy trials spanned 7, 10 or 14 days and the main outcome measures were cost per patient and marginal cost for additional cured patient calculated for a low cost-of-care setting (Spain), for a high-cost setting (USA), and for two follow-up strategies: (i) systematic 13C-urea breath test after eradication; (ii) clinical follow-up, breath-test if symptoms recurred., Results: Base-case analysis showed that for both the 13C-UBT and the clinical follow-up branches, lowest costs were obtained with 7-day schedules both in Spain and the USA. Sensitivity analysis showed that in Spain, 10-day therapies would have to increase 7-day cure rates by 10-12% to become cost-effective. In contrast, in the USA only a 3-5% increase was needed. The corresponding figures for 14-day therapy were 25-35% and 8-11%, respectively., Conclusions: Seven-day therapies seem the most cost-effective strategy. However, in high-cost areas the differences were less evident.

Aim: To perform a meta-analysis of studies comparing twice daily, one-week triple therapy with a proton pump inhibitor, clarithromycin (C) and amoxycillin (A) (PCA) vs. those using proton pump inhibitor, clarithromycin and a nitroimidazole (N) (PCN) for H. pylori eradication., Selection Criteria: Comparative randomized trials of PCA vs. PCN were included., Data Sources: PubMed database and abstracts from congresses until September 1999., Statistics: Meta-analysis was performed combining the Odds Ratios (OR) of the individual studies in a global OR (Peto method) both on an intention-to-treat (ITT) and on a per protocol (PP) basis., Results: Twenty-two studies fulfilled the inclusion criteria. Eighteen studies reported ITT and 20 PP analysis. Mean H. pylori eradication rates were 81% (95% CI: 79-83%) ITT, and 84% (82-86%) PP with PCA, and 81% (78-83%) ITT and 84% (82-86%) PP with PCN; the odds ratio for the effect of PCA vs. PCN was 1 (0.83-1.22) on an ITT, and 0.98 (0.8-1.2) on a PP basis. Subanalysis showed that mean H. pylori eradication efficacy with PC(250 b.d.)A was 81% (78-85%) ITT, vs. 86% (83-89%) with PC(250 b.d.)N. The odds ratio for this comparison was 0.68 (0.48-0.98). Finally, when comparing PC(500 b.d. )A against PC(250 b.d.)N ITT cure rates were 77% (74-80%), and 75% (72-78%) with an odds ratio of 1.18 (0.93-1.5)., Conclusion: Overall, one-week combination regimens of PCA and PCN present similar H. pylori eradication efficacy. Nevertheless, the PCN regimen obtains significantly better results when using low doses of C (250 mg b.d.).

Objective: To compare the efficacy of proton pump inhibitor vs. ranitidine bismuth citrate (RBC) with two antibiotics for 1 week in Helicobacter pylori eradication., Methods: Randomized trials comparing 1-week regimens with (i) proton pump inhibitor plus two antibiotics [clarithromycin (C) and amoxycillin (A) or a nitroimidazole (N)]; or (ii) RBC plus the same antibiotics. Eradication was confirmed by histology or 13C-urea breath test at least 4 weeks after therapy. Data sources included PubMed database and abstracts from congresses until October 1999. Statistical analysis was by meta-analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method)., Results: Twelve studies met the selection criteria. Nine compared proton pump inhibitor vs. RBC plus C and A, and five compared proton pump inhibitor vs. RBC plus C and N. With RBC, C and A, mean H. pylori eradication efficacy by intention-to-treat analysis (pooled data) was 76.6% (95% CI: 72-81%) and 73.7% (95% CI: 69-78%) with proton pump inhibitor, C and A. The OR for the effect of RBC vs. proton pump inhibitor (plus C and A) on H. pylori eradication was 1.15 (95% CI: 0.8-1.64%). Mean H. pylori eradication with RBC, C and N was 87. 2% (95% CI: 83-91%), and 74.9% (95% CI: 74-84%) with proton pump inhibitor plus these two antibiotics. The OR for the effect of RBC vs. proton pump inhibitor (plus C and N) on H. pylori eradication was 1.76 (95% CI: 1.08-2.85%)., Conclusion: RBC and proton pump inhibitor have similar efficacy for H. pylori eradication when given with C and A for 1 week, but RBC seems to have a higher efficacy than proton pump inhibitor when C and N are the co-prescribed antibiotics.

Background: Although triple therapies with a proton pump inhibitor, clarithromycin and either amoxycillin or metronidazole are the most widely accepted treatment for Helicobacter pylori infection, there is no consensus on how long treatment should be maintained for., Aim: To evaluate whether increasing the length of triple therapies beyond 7 days improves treatment efficacy., Methods: An extensive search of the literature was performed. Reports of randomized trials comparing different lengths of therapy were selected. Short (7-day) vs. long (10/14-day) therapies were compared, and three-way comparison of 7-day vs. 10-day, 10-day vs. 14-day and 7-day vs. 14-day therapies was performed. Meta-analysis was conducted using conventional shareware (Review Manager 4.0). The Peto Odds Ratio using a fixed model analysis was calculated for each comparison., Results: Thirteen studies were identified. Pooled 10- to 14-day therapies achieved better results than 7-day schedules. In head-to-head comparisons, only 14-day therapies were significantly better than 7-day treatments. Improvement in cure rates ranged from 7 to 9%. Comparisons of 7-day vs. 10-day and 10-day vs. 14-day also showed a non-significant trend towards better cure rates with longer therapies., Conclusions: Fourteen-day, proton pump inhibitor-based triple therapy achieves better results than 7-day schedules. Additional data are necessary to evaluate 10-day therapies.

: Quadruple rescue therapy requires a complex scheme with four drugs.: To evaluate the efficacy of ranitidine bismuth citrate-tetracycline-metronidazole rescue regimen, and to compare two different metronidazole dose schemes.: Prospective multicentre study including proton-pump inhibitor + clarithromycin + amoxicillin failures. Rescue regimen included two 7-day treatment: (i) ranitidine bismuth citrate (400 mg b.d.)-tetracycline (500 mg q.d.s.)-metronidazole (500 mg t.d.s.; RTM1); or (ii) the same regimen but with metronidazole 250 mg q.d.s. (RTM2). Eradication was confirmed with13C-urea breath test.: A total of 150 patients were included (58 RTM1, 92 RTM2). All patients but two (one in each group) returned after treatment. About 86% in group RTM1 and 95% in RTM2 correctly took all the medications (P = 0.076). Per-protocol eradication rates with RTM1 and RTM2 were 74 (95% CI: 60–84) and 69% (59–78). The intention-to-treat eradication rates were 64 (51–75) and 70% (59–78;P > 0.05). The type of regimen was not associated with eradication in the multivariate analysis. Adverse effects were more frequent with RTM1 (41%) than with RTM2 (30%;P > 0.05).: Seven-day triple rescue therapy with ranitidine bismuth citrate-tetracycline-metronidazole is effective forHelicobacter pylorieradication, and represents an encouraging alternative to quadruple therapy, with the advantage of simplicity. The administration of metronidazole every 6 h (together with tetracycline), and at a low dose (250 mg), achieves similar efficacy and is probably associated with a better compliance and a lower incidence of adverse effects. [ABSTRACT FROM AUTHOR]

: It is unknown whether proton pump inhibitors are superior to H2-receptor antagonists in Helicobacter pylori eradication regimens. : To perform a meta-analysis comparing the efficacy of both antisecretors when co-prescribed with antibiotics. : Randomized clinical trials comparing proton pump inhibitors vs. H2-receptor antagonists with the same antibiotics were selected. Data sources included PubMed, the Cochrane Controlled Trials Register and abstracts from congresses up to January 2002. A meta-analysis was performed by combining the odds ratios. : Twenty studies fulfilled the inclusion criteria. In the intention-to-treat analysis, the mean eradication rates with proton pump inhibitors and H2-receptor antagonists plus antibiotics were 74% [95% confidence interval (CI), 71–76%] and 69% (95% CI, 66–71%), respectively. The odds ratio for this comparison was 1.31 (95% CI, 1.09–1.58). The number needed to treat with proton pump inhibitors to achieve eradication success, compared with H2-receptor antagonists, was 25. When studies prescribing very high doses of H2-receptor antagonists (two of the outliers) were excluded, the odds ratio (for proton pump inhibitors vs. H2-receptor antagonists) increased to 1.37, the number needed to treat decreased to 20 and the heterogeneity between the studies decreased. : Overall, proton pump inhibitors are more effective than H2-receptor antagonists when prescribed at usual doses with antibiotics to eradicate H. pylori infection. [ABSTRACT FROM AUTHOR]

Summary Aim : To perform a systematic review of the efficacy of rabeprazole-based therapies in Helicobacter pylori eradication, and to conduct a meta-analysis comparing the efficacy of rabeprazole and other proton pump inhibitors when co-prescribed with antibiotics. Methods : Studies evaluating rabeprazole plus antibiotics were considered. Only randomized trials comparing rabeprazole and other proton pump inhibitors with antibiotics, and differing only in the proton pump inhibitor, were included in the meta-analysis. Electronic and manual bibliographic searches were conducted. The percentage (weighted mean) of successful eradication was calculated. Meta-analysis was performed by combining the odds ratios (OR) of the individual studies. Results : The eradication rates were as follows: 14-day rabeprazole–amoxicillin, 73%; rabeprazole–amoxicillin–clarithromycin for 3, 5, 7 and 10 days, 44%, 72%, 78% and 75%, respectively; low-dose rabeprazole (20 mg/day), amoxicillin and clarithromycin for 7 days, 81%; high-dose rabeprazole (40 mg/day), amoxicillin and clarithromycin for 7 days, 75%; 7-day rabeprazole–clarithromycin–nitroimidazole, 85%. Twelve comparative studies were included in the meta-analysis. The eradication rate with rabeprazole plus antibiotics was 79%; it was 77% with other proton pump inhibitors (OR = 1.15; 95% confidence interval, 0.93–1.42). Sub-analysis comparing rabeprazole at low doses (10 mg b.d.) with other proton pump inhibitors at standard doses (omeprazole 20 mg b.d. or lansoprazole 30 mg b.d.) showed no differences. Conclusions : Rabeprazole achieves similar H. pylori eradication rates to omeprazole and lansoprazole when co-prescribed with antibiotics. Low doses of rabeprazole (10 mg b.d.), when administered with two antibiotics, may be sufficient to eradicate H. pylori infection. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether proton pump inhibitors are more effective than H2-antagonists (H2-A) for the treatment of bleeding peptic ulcer. Data sources: PubMed database until January 2000. Study selection: Comparative randomized trials of proton pump inhibitors (omeprazole, lansoprazole, or pantoprazole) vs. H2-A (cimetidine, ranitidine or famotidine). Data extraction: Meta-analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method). Outcomes evaluated: Persistent or recurrent bleeding, need for surgery, or mortality. Data synthesis: Eleven studies fulfilled the inclusion criteria and contained data for at least one of the planned comparisons. Persistent or recurrent bleeding was reported in 6.7% (95% CI: 4.9–8.6%) of the patients treated with proton pump inhibitors, and in 13.4% (95% CI: 10.8–16%) of those treated with H2-A (OR 0.4; 95% CI: 0.27–0.59) (χ2-homogeneity test, 18; P=0.09). Surgery was needed in 5.2% (95% CI: 3.4–6.9%) of the patients treated with proton pump inhibitors, and in 6.9% (95% CI: 4.9–8.9%) of the patients treated with H2-A (OR 0.7; 95% CI: 0.43–1.13). Respective percentages for mortality were 1.6% (95% CI: 0.9–2.9%) and 2.2% (95% CI: 1.3–3.7%) (OR 0.69; 95% CI: 0.31–1.57). Sub-analysis: Five studies evaluated the effect of both therapies given in bolus injections on persistent or recurrent bleeding rate, which was 6% (95% CI: 3.6–8.3%) and 8.1% (95% CI: 5.3–10.9%), respectively (OR, 0.57; 95% CI: 0.31–1.05). Persistent or recurrent bleeding in high risk patients (Forrest Ia, Ib and IIa) occurred in 13.2% (95% CI: 7.9–8%) of the patients treated with proton pump inhibitors and in 34.5% (27–42%) of those treated with H2-A (OR 0.28; 95% CI: 0.16–0.48). In patients not having endoscopic therapy, persistent or recurrent bleeding was reported, respectively, in 4.3% (95% CI: 2.7–6.7%) and in 12% (95% CI: 8.7–15%) (OR 0.24; 95% CI: 0.13–0.43). Less marked differences were observed in patients having adjunct endoscopic therapy: 10.3% (95% CI: 6.7–13.8%) and 15.2% (11.1–19.3%) (OR 0.59; 95% CI: 0.36–0.97). Moreover, the significance disappeared in this group when a single outlier study was excluded. Conclusions: Proton pump inhibitors are more effective than H2-A in preventing persistent or recurrent bleeding from peptic ulcer, although this advantage seems to be more evident in patients not having adjunct sclerosis therapy. This beneficial effect seems to be similar or even more marked in patients with Forrest Ia, Ib or IIa ulcers. However, proton pump inhibitors are not more effective than H2-A for reducing surgery or mortality rates. Nevertheless, the data are too scarce and heterogeneous to draw definitive conclusions, and further comparative trials are clearly warranted. [ABSTRACT FROM AUTHOR]

Aim: It is unknown whether proton pump inhibitors (PPIs) are superior to H[sub 2] antagonists (H[sub 2]-antag) in H. pylori eradication regimens. Our aim was to perform a meta-analysis comparing the efficacy of both antisecretors when co-prescribed with antibiotics. Methods: Selection criteria: Comparative randomized trials with at least two branches of treatment consisting of PPIs vs. H[sub 2]-antag with the same antibiotics. Data sources: PubMed database, Cochrane Controlled Trials Register, and abstracts from congresses until January 2002. Statistics: Meta-analysis combining the Odds Ratios (OR) of the individual studies in a global OR (Random-effects-model) and multiple regression analysis (meta-regression). Results: Included studies: 16 studies were identified on an intentionto-treat (ITT) basis (including 1,193 patients treated with PPIs and 1,181 with H[sub 2]-antag) and 20 studies on a per-protocol (PP) basis (1,217 patients treated with PPI and 1,204 with H[sub 2]-antag). Efficacy: Mean eradication rate (ITT) with PPIs plus antibiotics was 75%, and 68% with H[sub 2]-antag. The global OR for the effect of PPIs vs. H[sub 2]-antag on H. pylori eradication was 1.48 (95%CI = 1.23-1.79). NNT (number needed to treat) with PPIs to achieve eradication success, compared with H[sub 2]-antag, was 17. PP eradication rates with PPIs and H[sub 2]-antag were 82% and 78% respectively (OR = 1.37; 95%CI = 1.11-1.69). Subanalysis: When studies prescribing very high doses of H[sub 2]-antag [(Gschwantler et al (famotidine 160 mg/day) and Tham et al (ranitidine 1,200 mg/day), two of the outliers) were excluded, heterogeneity decreased and OR increased, both by ITT (1.56; 1.29-1.89) and PP (1.52; 1.22-1.9). Meta-regression including duration of treatment (7 vs. 10-14 days), number of antibiotics (double vs. triple) and dose of H[sub 2]-antag (low-normal vs. high) demonstrated that H[sub 2]-antag dose was the only variable associated with differences in H. pylori eradication.... [ABSTRACT FROM AUTHOR]