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JAMA Internal Medicine Nov 2014Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor (PPI) followed by continuous PPI infusion after endoscopic therapy in patients with... (Comparative Study)
Comparative Study Meta-Analysis Review
IMPORTANCE
Current guidelines recommend an intravenous bolus dose of a proton pump inhibitor (PPI) followed by continuous PPI infusion after endoscopic therapy in patients with high-risk bleeding ulcers. Substitution of intermittent PPI therapy, if similarly effective as bolus plus continuous-infusion PPI therapy, would decrease the PPI dose, costs, and resource use.
OBJECTIVE
To compare intermittent PPI therapy with the currently recommended bolus plus continuous-infusion PPI regimen for reduction of ulcer rebleeding.
DATA SOURCES
Searches included MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases through December 2013; US and European gastroenterology meeting abstracts from 2009 to 2013; and bibliographies of systematic reviews.
STUDY SELECTION
Randomized trials of patients with endoscopically treated high-risk bleeding ulcers (active bleeding, nonbleeding visible vessels, and adherent clots) comparing intermittent doses of PPIs and the currently recommended regimen (80-mg intravenous bolus dose of a PPI followed by an infusion of 8 mg/h for 72 hours).
DATA EXTRACTION AND SYNTHESIS
Duplicate independent data extraction and risk-of-bias assessment were performed. Data were pooled using a fixed-effects model or a random effects model if statistical heterogeneity was present.
MAIN OUTCOMES AND MEASURES
The primary outcome was rebleeding within 7 days; additional predefined outcomes included rebleeding within 3 and 30 days, need for urgent intervention, mortality, red blood cell transfusion, and length of hospital stay. The primary hypothesis, defined before initiation of the literature review, was that intermittent use of PPIs was noninferior to bolus plus continuous infusion of PPIs, with the noninferiority margin predefined as an absolute risk difference of 3%.
RESULTS
The risk ratio of rebleeding within 7 days for intermittent vs bolus plus continuous infusion of PPIs was 0.72 (upper boundary of 1-sided 95% CI, 0.97) and the absolute risk difference was -2.64% (upper boundary of 1-sided 95% CI, -0.28%, which is well below the predefined noninferiority margin of 3%). Risk ratios for rebleeding within 30 days and 3 days, mortality, and urgent interventions were less than 1 and mean differences for blood transfusion and hospital length of stay were less than 0, indicating that no summary estimate showed an increased risk with intermittent therapy. The upper boundaries of 95% CIs for absolute risk differences were less than 1.50% for all predefined rebleeding outcomes.
CONCLUSIONS AND RELEVANCE
Intermittent PPI therapy is comparable to the current guideline-recommended regimen of intravenous bolus plus a continuous infusion of PPIs in patients with endoscopically treated high-risk bleeding ulcers. Guidelines should be revised to recommend intermittent PPI therapy.
Topics: Humans; Infusions, Intravenous; Peptic Ulcer; Peptic Ulcer Hemorrhage; Proton Pump Inhibitors
PubMed: 25201154
DOI: 10.1001/jamainternmed.2014.4056 -
Journal of Gastroenterology Apr 2021The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an...
The Japanese Society of Gastroenterology (JSGE) revised the third edition of evidence-based clinical practice guidelines for peptic ulcer disease in 2020 and created an English version. The revised guidelines consist of nine items: epidemiology, hemorrhagic gastric and duodenal ulcers, Helicobacter pylori (H. pylori) eradication therapy, non-eradication therapy, drug-induced ulcers, non-H. pylori, and nonsteroidal anti-inflammatory drug (NSAID) ulcers, remnant gastric ulcers, surgical treatment, and conservative therapy for perforation and stenosis. Therapeutic algorithms for the treatment of peptic ulcers differ based on ulcer complications. In patients with NSAID-induced ulcers, NSAIDs are discontinued and anti-ulcer therapy is administered. If NSAIDs cannot be discontinued, the ulcer is treated with proton pump inhibitors (PPIs). Vonoprazan (VPZ) with antibiotics is recommended as the first-line treatment for H. pylori eradication, and PPIs or VPZ with antibiotics is recommended as a second-line therapy. Patients who do not use NSAIDs and are H. pylori negative are considered to have idiopathic peptic ulcers. Algorithms for the prevention of NSAID- and low-dose aspirin (LDA)-related ulcers are presented in this guideline. These algorithms differ based on the concomitant use of LDA or NSAIDs and ulcer history or hemorrhagic ulcer history. In patients with a history of ulcers receiving NSAID therapy, PPIs with or without celecoxib are recommended and the administration of VPZ is suggested for the prevention of ulcer recurrence. In patients with a history of ulcers receiving LDA therapy, PPIs or VPZ are recommended and the administration of a histamine 2-receptor antagonist is suggested for the prevention of ulcer recurrence.
Topics: Humans; Anti-Bacterial Agents; Evidence-Based Practice; Japan; Peptic Ulcer; Proton Pump Inhibitors
PubMed: 33620586
DOI: 10.1007/s00535-021-01769-0 -
Alimentary Pharmacology & Therapeutics Jan 2021Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Functional dyspepsia (FD) is a relapsing and remitting condition affecting between 5% and 10% of people. Efficacious therapies are available, but their relative efficacy is unknown.
AIM
To perform a systematic review with network meta-analysis to resolve this uncertainty.
METHODS
We searched the medical literature through July 2020 for randomised controlled trials (RCTs) assessing efficacy of drugs for adults with FD, compared with each other, or placebo. Trials reported a dichotomous assessment of symptom status after completion of therapy. We pooled data using a random effects model. Efficacy was reported as a pooled relative risk (RR) of remaining symptomatic with a 95% confidence interval (CI) to summarise efficacy of each comparison tested. Relative ranking was assessed with surface under the cumulative ranking curve (SUCRA) probabilities.
RESULTS
We identified 71 eligible RCTs (19 243 participants). Tricyclic antidepressants (TCAs) were ranked second for efficacy (RR of remaining symptomatic = 0.71; 95% CI 0.58-0.87, SUCRA 0.87), and first when only low risk of bias trials were included. Most RCTs that used TCAs recruited patients who were refractory to other drugs included in the network. Although sulpiride or levosulpiride were ranked first for efficacy (RR = 0.49; 95% CI 0.36-0.69, SUCRA 0.99), trial quality was low and only 86 patients received active therapy. TCAs were more likely to cause adverse events than placebo.
CONCLUSIONS
TCAs, histamine- receptor antagonists, standard- and low-dose proton pump inhibitors, sulpiride or levosulpiride, itopride and acotiamide were all more efficacious than placebo for FD.
Topics: Adult; Dyspepsia; Histamine H2 Antagonists; Humans; Network Meta-Analysis; Pharmaceutical Preparations; Proton Pump Inhibitors
PubMed: 32936964
DOI: 10.1111/apt.16072 -
World Journal of Gastroenterology Mar 2016To evaluate whether Helicobacter pylori (H. pylori) eradication therapy benefits patients with functional dyspepsia (FD). (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate whether Helicobacter pylori (H. pylori) eradication therapy benefits patients with functional dyspepsia (FD).
METHODS
Randomized controlled trials (RCTs) investigating the efficacy and safety of H. pylori eradication therapy for patients with functional dyspepsia published in English (up to May 2015) were identified by searching PubMed, EMBASE, and The Cochrane Library. Pooled estimates were measured using the fixed or random effect model. Overall effect was expressed as a pooled risk ratio (RR) or a standard mean difference (SMD). All data were analyzed with Review Manager 5.3 and Stata 12.0.
RESULTS
This systematic review included 25 RCTs with a total of 5555 patients with FD. Twenty-three of these studies were used to evaluate the benefits of H. pylori eradication therapy for symptom improvement; the pooled RR was 1.23 (95%CI: 1.12-1.36, P < 0.0001). H. pylori eradication therapy demonstrated symptom improvement during long-term follow-up at ≥ 1 year (RR = 1.24; 95%CI: 1.12-1.37, P < 0.0001) but not during short-term follow-up at < 1 year (RR = 1.26; 95%CI: 0.83-1.92, P = 0.27). Seven studies showed no benefit of H. pylori eradication therapy on quality of life with an SMD of -0.01 (95%CI: -0.11 to 0.08, P = 0.80). Six studies demonstrated that H. pylori eradication therapy reduced the development of peptic ulcer disease compared to no eradication therapy (RR = 0.35; 95%CI: 0.18-0.68, P = 0.002). Eight studies showed that H. pylori eradication therapy increased the likelihood of treatment-related side effects compared to no eradication therapy (RR = 2.02; 95%CI: 1.12-3.65, P = 0.02). Ten studies demonstrated that patients who received H. pylori eradication therapy were more likely to obtain histologic resolution of chronic gastritis compared to those who did not receive eradication therapy (RR = 7.13; 95%CI: 3.68-13.81, P < 0.00001).
CONCLUSION
The decision to eradicate H. pylori in patients with functional dyspepsia requires individual assessment.
Topics: Adult; Anti-Bacterial Agents; Chi-Square Distribution; Drug Therapy, Combination; Dyspepsia; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Middle Aged; Odds Ratio; Proton Pump Inhibitors; Remission Induction; Risk Factors; Treatment Outcome
PubMed: 27022230
DOI: 10.3748/wjg.v22.i12.3486 -
Diseases of the Esophagus : Official... May 2017In patients with gastroesophageal reflux disease (GERD) and erosive esophagitis, treatment with proton pump inhibitors (PPIs) is highly effective. However, in some... (Meta-Analysis)
Meta-Analysis Review
In patients with gastroesophageal reflux disease (GERD) and erosive esophagitis, treatment with proton pump inhibitors (PPIs) is highly effective. However, in some patients, especially those with nonerosive reflux disease or atypical GERD symptoms, acid-suppressive therapy with PPIs is not as successful. Alginates are medications that work through an alternative mechanism by displacing the postprandial gastric acid pocket. This study performed a systematic review and meta-analysis to examine the benefit of alginate-containing compounds in the treatment of patients with symptoms of GERD. PubMed/MEDLINE, Embase, and the Cochrane library electronic databases were searched through October 2015 for randomized controlled trials comparing alginate-containing compounds to placebo, antacids, histamine-2 receptor antagonists (H2RAs), or PPIs for the treatment of GERD symptoms. Additional studies were identified through a bibliography review. Non-English studies and those with pediatric patients were excluded. Meta-analyses were performed using random-effect models to calculate odds ratios (OR). Heterogeneity between studies was estimated using the I2 statistic. Analyses were stratified by type of comparator. The search strategy yielded 665 studies and 15 (2.3%) met inclusion criteria. Fourteen were included in the meta-analysis (N = 2095 subjects). Alginate-based therapies increased the odds of resolution of GERD symptoms when compared to placebo or antacids (OR: 4.42; 95% CI 2.45-7.97) with a moderate degree of heterogeneity between studies (I2 = 71%, P = .001). Compared to PPIs or H2RAs, alginates appear less effective but the pooled estimate was not statistically significant (OR: 0.58; 95% CI 0.27-1.22). Alginates are more effective than placebo or antacids for treating GERD symptoms.
Topics: Adult; Alginates; Antacids; Female; Gastroesophageal Reflux; Glucuronic Acid; Hexuronic Acids; Histamine H2 Antagonists; Humans; Male; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28375448
DOI: 10.1093/dote/dow020 -
Journal of Gastroenterology and... Dec 2022Potassium-competitive acid blocker (PCAB) is a recent alternative to proton pump inhibitor (PPI) for potent acid suppression. The current systematic review and... (Meta-Analysis)
Meta-Analysis
A comparison of efficacy and safety of potassium-competitive acid blocker and proton pump inhibitor in gastric acid-related diseases: A systematic review and meta-analysis.
BACKGROUND AND AIM
Potassium-competitive acid blocker (PCAB) is a recent alternative to proton pump inhibitor (PPI) for potent acid suppression. The current systematic review and meta-analysis aimed to compare the efficacy and safety of PCAB versus PPI in treating gastric acid-related diseases.
METHODS
We searched up to June 5, 2022, for randomized controlled trials of gastric acid-related diseases that included erosive esophagitis, symptomatic gastroesophageal reflux disease (GERD), peptic ulcers, and Helicobacter pylori infection. The pooled risk ratio (RR) was evaluated for the efficacy outcome and treatment-emergent adverse events (TEAEs) as the safety outcome. Sensitivity analyses were performed to test the robustness of the study findings.
RESULTS
Of the 710 screened studies, 19 studies including 7023 participants were analyzed. The RRs for the healing of erosive esophagitis with Vonoprazan versus PPI were 1.09 (95% confidence interval [CI] 1.03-1.14), 1.03 (95% CI 1.00-1.07), and 1.02 (95% CI 1.00-1.05) in Weeks 2, 4, and 8, respectively. There were no differences in the improvement of GERD symptoms and healing of gastric and duodenal ulcers between PCAB and PPI. The pooled eradication rates of H. pylori were significantly higher in Vonoprazan versus PPI first-line treatment (RR 1.13; 95% CI 1.04-1.22). The overall RR of TEAEs with Vonoprazan versus PPI was 1.08 (95% CI 0.89-1.31). Overall, the risk of bias was low to some concerns. Furthermore, sensitivity analyses confirmed the robustness of the study's conclusion.
CONCLUSION
Vonoprazan is superior to PPI in first-line H. pylori eradication and erosive esophagitis but non-inferior in other gastric acid-related diseases. Likewise, short-term safety is comparable in both treatment groups.
Topics: Humans; Gastric Acid; Proton Pump Inhibitors; Potassium; Helicobacter Infections; Helicobacter pylori
PubMed: 36181401
DOI: 10.1111/jgh.16017 -
Frontiers in Pharmacology 2022Proton pump inhibitors (PPIs) are usually prescribed to prevent gastrointestinal (GI) complications in patients receiving dual antiplatelet therapy (DAPT). This...
Efficacy and safety of concomitant use of proton pump inhibitors with aspirin-clopidogrel dual antiplatelet therapy in coronary heart disease: A systematic review and meta-analysis.
Proton pump inhibitors (PPIs) are usually prescribed to prevent gastrointestinal (GI) complications in patients receiving dual antiplatelet therapy (DAPT). This systematic review and meta-analysis aimed to explore the efficacy and safety of the concomitant use of PPIs with aspirin-clopidogrel DAPT in patients with Coronary heart disease (CHD). The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from inception to August 2022 for eligible studies. The adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Subgroup analysis was conducted according to different PPI subtypes, populations, follow-up times and study types. This study was registered on PROSPERO (CRD42022332195). A total of 173,508 patients from 18 studies [2 randomized controlled trials (RCTs), 3 analyses of RCTs, and 13 cohort studies] were included in this study. Pooled data revealed that coadministration of PPIs significantly increased the risk of major adverse cardiovascular events (MACEs) (HR = 1.15, 95% CI = 1.06-1.26, = .001) and reduced the risk of gastrointestinal (GI) complications (HR = 0.44, 95% CI = 0.30-0.64, .0001). Subgroup analysis results showed that the esomeprazole users and patients with coronary stenting in the PPI group were associated with an increased risk of MACEs compared with the non-PPI group. The occurrence of MACEs in PPI users was more common than that in non-PPI users in long-term follow-up (≥12 months) studies and in the observational studies. There was no significant differences in the incidences of net clinical adverse events (NACEs), all-cause mortality, or cardiac death between the two groups. In patients with CHD, the concomitant use of PPIs with aspirin and clopidogrel was associated with a reduced risk of GI complications but could increase the rates of MACEs (particularly in patients receiving esomeprazole or with coronary stenting). There was no clear evidence of an association between PPI use and NACEs, all-cause mortality, or cardiac death. The results could have been affected by the follow-up time and study type. Further large-scale RCTs with long-term follow-up are needed.
PubMed: 36703730
DOI: 10.3389/fphar.2022.1021584 -
Gastroenterology May 2016Eradication of Helicobacter pylori infection has been reported to reduce the risk of gastric cancer among asymptomatic individuals in high-risk areas. The magnitude of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Eradication of Helicobacter pylori infection has been reported to reduce the risk of gastric cancer among asymptomatic individuals in high-risk areas. The magnitude of benefit of H pylori eradication in populations with different levels of gastric cancer risk and in different clinical scenarios is unclear. We performed a systematic review and meta-analysis of randomized controlled trials and observational studies to investigate the effects of H pylori eradication on the incidence of gastric cancer.
METHODS
We searched PubMed, Cochrane Library, and ClinicalTrials.gov, reviewing titles and abstracts of studies of the effects of eradication of H pylori infection on risk of gastric cancer, through May 2015. We also searched bibliographies of included studies, related reviews, and abstracts presented at Digestive Disease Week. Twenty-four eligible studies (22 research manuscripts and 2 abstracts) were included in our meta-analysis (715 incident gastric cancers among a total of 48,064 individuals/340,255 person-years). We assessed the effects, as well as their modification by baseline gastric cancer incidence, study design (randomized trial vs observational study), clinical scenario (asymptomatic infected individuals vs individuals after endoscopic resection of early gastric cancer), demographic characteristics of patients (age and sex), and duration of follow-up.
RESULTS
After adjustment for baseline gastric cancer incidence, individuals with eradication of H pylori infection had a lower incidence of gastric cancer than those who did not receive eradication therapy (pooled incidence rate ratio = 0.53; 95% confidence interval: 0.44-0.64). There was little heterogeneity among studies. Baseline gastric cancer incidence modified the benefit of H pylori eradication (P = .037 for interaction); the incidence rate ratio of gastric cancer decreased in a nonlinear fashion with increasing baseline incidence of gastric cancer (P = .018, in comparison with the linear model). The benefit also modestly increased with age (P = .023 for interaction), but this might be due to correlation between age and baseline gastric cancer incidence. Eradication provided significant benefit for asymptomatic infected individuals (pooled incidence rate ratio, 0.62; 95% CI: 0.49-0.79) and individuals after endoscopic resection of gastric cancers (pooled incidence rate ratio, 0.46; 95% CI: 0.35-0.60). The benefits of H pylori eradication did not differ with study design, sex, or follow-up period.
CONCLUSIONS
In a systematic review and meta-analysis, we associated eradication of H pylori infection with a reduced incidence of gastric cancer. The benefits of eradication vary with baseline gastric cancer incidence, but apply to all levels of baseline risk.
Topics: Anti-Bacterial Agents; Drug Therapy, Combination; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Odds Ratio; Protective Factors; Proton Pump Inhibitors; Risk Assessment; Risk Factors; Stomach Neoplasms; Treatment Outcome
PubMed: 26836587
DOI: 10.1053/j.gastro.2016.01.028 -
Clinical Gastroenterology and... Jun 2018Although proton pump inhibitors (PPIs) are widely used, their relative potency and ideal dosing regimens remain unclear. We analyzed data from randomized clinical trials... (Comparative Study)
Comparative Study
Although proton pump inhibitors (PPIs) are widely used, their relative potency and ideal dosing regimens remain unclear. We analyzed data from randomized clinical trials that performed pH testing in patients receiving solid-dose PPI formulations (omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole) for a minimum of 5 days. We used omeprazole equivalency and the surrogate biomarker, percentage time pH > 4 over a 24-hour period (pH4time), to compare PPI effectiveness for different PPIs given once, twice, or 3 times daily. We found that increasing strength of once-daily PPIs (9-64 mg omeprazole equivalents) increased pH4time linearly from approximately 10.0 to 15.6 hours; higher doses produced no further increase in pH4time. Increasing the frequency to twice-daily PPI increased pH4time linearly, from approximately 15.8 to 21.0 hours. Three-times daily PPIs performed similarly to twice-daily PPIs. The costs of PPIs varied greatly, but the cost variation was not directly related to potency. We conclude that PPIs can be used interchangeably based on potency. Using twice-daily PPIs is more effective in increasing efficacy increasing once-daily PPI dosage. Omeprazole and lansoprazole (30 mg) and 20 mg of esomeprazole rabeprazole are functionally equivalent.
Topics: Gastroesophageal Reflux; Humans; Hydrogen-Ion Concentration; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28964908
DOI: 10.1016/j.cgh.2017.09.033 -
British Journal of Clinical Pharmacology Nov 2021The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes. (Meta-Analysis)
Meta-Analysis Review
AIMS
The objective of this paper is to systematically review the literature on drug-drug interactions with warfarin, with a focus on patient-important clinical outcomes.
METHODS
MEDLINE, EMBASE and the International Pharmaceutical Abstract (IPA) databases were searched from January 2004 to August 2019. We included studies describing drug-drug interactions between warfarin and other drugs. Screening and data extraction were conducted independently and in duplicate. We synthesized pooled odds ratios (OR) with 95% confidence intervals (CIs), comparing warfarin plus another medication to warfarin alone. We assessed the risk of bias at the study level and evaluated the overall certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Of 42 013 citations identified, a total of 72 studies reporting on 3 735 775 patients were considered eligible, including 11 randomized clinical trials and 61 observational studies. Increased risk of clinically relevant bleeding when added to warfarin therapy was observed for antiplatelet (AP) regimens (OR = 1.74; 95% CI 1.56-1.94), many antimicrobials (OR = 1.63; 95% CI 1.45-1.83), NSAIDs including COX-2 NSAIDs (OR = 1.83; 95% CI 1.29-2.59), SSRIs (OR = 1.62; 95% CI 1.42-1.85), mirtazapine (OR = 1.75; 95% CI 1.30-2.36), loop diuretics (OR = 1.92; 95% CI 1.29-2.86) among others. We found a protective effect of proton pump inhibitors (PPIs) against warfarin-related gastrointestinal (GI) bleeding (OR = 0.69; 95% CI 0.64-0.73). No significant effect on thromboembolic events or mortality of any drug group used with warfarin was found, including single or dual AP regimens.
CONCLUSIONS
This review found low to moderate certainty evidence supporting the interaction between warfarin and a small group of medications, which result in increased bleeding risk. PPIs are associated with reduced hospitalization for upper GI bleeding for patients taking warfarin. Further studies are required to better understand drug-drug interactions leading to thromboembolic outcomes or death.
Topics: Anticoagulants; Drug Interactions; Gastrointestinal Hemorrhage; Humans; Pharmaceutical Preparations; Randomized Controlled Trials as Topic; Warfarin
PubMed: 33769581
DOI: 10.1111/bcp.14833