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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 -
The Cochrane Database of Systematic... Jan 2022Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to... (Review)
Review
BACKGROUND
Upper gastrointestinal (GI) bleeding is a common reason for emergency hospital admission. Proton pump inhibitors (PPIs) reduce gastric acid production and are used to manage upper GI bleeding. However, there is conflicting evidence regarding the clinical efficacy of proton pump inhibitors initiated before endoscopy in people with upper gastrointestinal bleeding.
OBJECTIVES
To assess the effects of PPI treatment initiated prior to endoscopy in people with acute upper GI bleeding.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Embase and CINAHL databases and major conference proceedings to October 2008, for the previous versions of this review, and in April 2018, October 2019, and 3 June 2021 for this update. We also contacted experts in the field and searched trial registries and references of trials for any additional trials.
SELECTION CRITERIA
We selected randomised controlled trials (RCTs) that compared treatment with a PPI (oral or intravenous) versus control treatment with either placebo, histamine-2 receptor antagonist (HRA) or no treatment, prior to endoscopy in hospitalised people with uninvestigated upper GI bleeding.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed study eligibility, extracted study data and assessed risk of bias. Outcomes assessed at 30 days were: mortality (our primary outcome), rebleeding, surgery, high-risk stigmata of recent haemorrhage (active bleeding, non-bleeding visible vessel or adherent clot) at index endoscopy, endoscopic haemostatic treatment at index endoscopy, time to discharge, blood transfusion requirements and adverse effects. We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included six RCTs comprising 2223 participants. No new studies have been published after the literature search performed in 2008 for the previous version of this review. Of the included studies, we considered one to be at low risk of bias, two to be at unclear risk of bias, and three at high risk of bias. Our meta-analyses suggest that pre-endoscopic PPI use may not reduce mortality (OR 1.14, 95% CI 0.76 to 1.70; 5 studies; low-certainty evidence), and may reduce rebleeding (OR 0.81, 95% CI 0.62 to 1.06; 5 studies; low-certainty evidence). In addition, pre-endoscopic PPI use may not reduce the need for surgery (OR 0.91, 95% CI 0.65 to 1.26; 6 studies; low-certainty evidence), and may not reduce the proportion of participants with high-risk stigmata of recent haemorrhage at index endoscopy (OR 0.80, 95% CI 0.52 to 1.21; 4 studies; low-certainty evidence). Pre-endoscopic PPI use likely reduces the need for endoscopic haemostatic treatment at index endoscopy (OR 0.68, 95% CI 0.50 to 0.93; 3 studies; moderate-certainty evidence). There were insufficient data to determine the effect of pre-endoscopic PPI use on blood transfusions (2 studies; meta-analysis not possible; very low-certainty evidence) and time to discharge (1 study; very low-certainty evidence). There was no substantial heterogeneity amongst trials in any analysis.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that PPI treatment initiated before endoscopy for upper GI bleeding likely reduces the requirement for endoscopic haemostatic treatment at index endoscopy. However, there is insufficient evidence to conclude whether pre-endoscopic PPI treatment increases, reduces or has no effect on other clinical outcomes, including mortality, rebleeding and need for surgery. Further well-designed RCTs that conform to current standards for endoscopic haemostatic treatment and appropriate co-interventions, and that ensure high-dose PPIs are only given to people who received endoscopic haemostatic treatment, regardless of initial randomisation, are warranted. However, as it may be unrealistic to achieve the optimal information size, pragmatic multicentre trials may provide valuable evidence on this topic.
Topics: Acute Disease; Endoscopy; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Proton Pump Inhibitors
PubMed: 34995368
DOI: 10.1002/14651858.CD005415.pub4 -
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 -
Clinical Pharmacology and Therapeutics Jun 2021Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric...
Proton pump inhibitors (PPIs) are widely used for acid suppression in the treatment and prevention of many conditions, including gastroesophageal reflux disease, gastric and duodenal ulcers, erosive esophagitis, Helicobacter pylori infection, and pathological hypersecretory conditions. Most PPIs are metabolized primarily by cytochrome P450 2C19 (CYP2C19) into inactive metabolites, and CYP2C19 genotype has been linked to PPI exposure, efficacy, and adverse effects. We summarize the evidence from the literature and provide therapeutic recommendations for PPI prescribing based on CYP2C19 genotype (updates at www.cpicpgx.org). The potential benefits of using CYP2C19 genotype data to guide PPI therapy include (i) identifying patients with genotypes predictive of lower plasma exposure and prescribing them a higher dose that will increase the likelihood of efficacy, and (ii) identifying patients on chronic therapy with genotypes predictive of higher plasma exposure and prescribing them a decreased dose to minimize the risk of toxicity that is associated with long-term PPI use, particularly at higher plasma concentrations.
Topics: Cytochrome P-450 CYP2C19; Gastroesophageal Reflux; Genotype; Humans; Pharmacogenetics; Proton Pump Inhibitors
PubMed: 32770672
DOI: 10.1002/cpt.2015 -
BMJ Open Feb 2020To conduct a systematic review of systematic reviews and national guidelines to assess the effectiveness of four treatment approaches (manual therapy, probiotics, proton... (Comparative Study)
Comparative Study
OBJECTIVE
To conduct a systematic review of systematic reviews and national guidelines to assess the effectiveness of four treatment approaches (manual therapy, probiotics, proton pump inhibitors and simethicone) on colic symptoms including infant crying time, sleep distress and adverse events.
METHODS
We searched PubMed, Embase, Cochrane and Mantis for studies published between 2009 and 2019. Inclusion criteria were systematic reviews and guidelines that used evidence and expert panel opinion. Three reviewers independently selected articles by title, abstract and full paper review. Data were extracted by one reviewer and checked by a second. Selected studies were assessed for quality using modified standardised checklists by two authors. Meta-analysed data for our outcomes of interest were extracted and narrative conclusions were assessed.
RESULTS
Thirty-two studies were selected. High-level evidence showed that probiotics were most effective for reducing crying time in breastfed infants (range -25 min to -65 min over 24 hours). Manual therapies had moderate to low-quality evidence showing reduced crying time (range -33 min to -76 min per 24 hours). Simethicone had moderate to low evidence showing no benefit or negative effect. One meta-analysis did not support the use of proton pump inhibitors for reducing crying time and fussing. Three national guidelines unanimously recommended the use of education, parental reassurance, advice and guidance and clinical evaluation of mother and baby. Consensus on other advice and treatments did not exist.
CONCLUSIONS
The strongest evidence for the treatment of colic was probiotics for breastfed infants, followed by weaker but favourable evidence for manual therapy indicated by crying time. Both forms of treatment carried a low risk of serious adverse events. The guidance reviewed did not reflect these findings.
PROSPERO REGISTRATION NUMBER
CRD42019139074.
Topics: Antifoaming Agents; Colic; Humans; Infant; Musculoskeletal Manipulations; Practice Guidelines as Topic; Probiotics; Proton Pump Inhibitors; Review Literature as Topic; Simethicone; Treatment Outcome
PubMed: 32102827
DOI: 10.1136/bmjopen-2019-035405 -
The American Journal of Medicine Oct 2022The role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of antisecretory drugs for the prevention of upper gastrointestinal bleeding in patients using anticoagulants is unclear. We investigated this question in a systematic review and meta-analysis.
METHODS
We searched Embase, PubMed, Web of Science, Scopus, the Cochrane Library, and clinicaltrials.gov thru April 2021 for controlled randomized trials and observational studies evaluating the association of proton pump inhibitors (PPIs) or H2-receptor antagonists with overt upper gastrointestinal bleeding in patients using anticoagulants. Independent duplicate review, data extraction, and risk of bias assessment were performed. Observational studies were included only if they provided results controlled for at least 2 variables. Meta-analyses were performed using random effects models.
RESULTS
Six observational studies and 1 randomized trial were included. All but 1 study had low risk of bias. None of the studies excluded patients with concomitant aspirin or nonsteroidal anti-inflammatory drug use. For PPIs, the pooled relative risk of upper gastrointestinal bleeding was 0.67 (95% confidence interval 0.61, 0.74) with low statistical heterogeneity (I = 15%). Individual studies showed greater treatment effect in patients with higher risk for upper gastrointestinal bleeding (eg, nonsteroidal anti-inflammatory drug or aspirin use, elevated bleeding risk score). A single observational study evaluating the association of H2-receptor antagonists with upper gastrointestinal bleeding found a relative risk of 0.69 (95% confidence interval 0.24-2.02).
CONCLUSIONS
Evidence drawn mostly from observational studies with low risk of bias demonstrate that PPIs reduce upper gastrointestinal bleeding in patients prescribed oral anticoagulants. The benefit appears to be most clearcut and substantial in patients with elevated risk of upper gastrointestinal bleeding.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Anticoagulants; Aspirin; Gastrointestinal Agents; Gastrointestinal Hemorrhage; Histamine H2 Antagonists; Humans; Observational Studies as Topic; Proton Pump Inhibitors
PubMed: 35679879
DOI: 10.1016/j.amjmed.2022.05.031 -
Journal of Gastroenterology and... Aug 2019Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIM
Gastroesophageal reflux disease (GERD) is a common disease caused by reflux of gastric contents to the esophagus. Proton-pump inhibitors (PPIs) are recommended as a first-line therapy to treat GERD. Recently, a new potassium-competitive acid blocker, vonoprazan, was launched in Japan. We aimed to evaluate the comparative efficacy of vonoprazan and other PPIs in healing GERD.
METHODS
We used MEDLINE and the Cochrane Central Register of Controlled Trials to search the literature. Double-blind randomized controlled trials for PPIs and/or vonoprazan that were published in English or Japanese and assessed healing effects in adult GERD patients were included. To estimate the comparative efficacy of treatments, we performed a Bayesian network meta-analysis to assess the consistency assumption.
RESULTS
Of 4001 articles identified in the database, 42 studies were eligible. One study was hand-searched and added to the analysis. For the main analysis of healing effects at 8 weeks, odds ratios (ORs) of vonoprazan (20 mg daily) to esomeprazole (20 mg), rabeprazole (20 mg), lansoprazole (30 mg), and omeprazole (20 mg) were 2.29 (95% credible interval, 0.79-7.06), 3.94 (1.15-14.03), 2.40 (0.90-6.77), and 2.71 (0.98-7.90), respectively. Subgroup analysis for patients with severe esophagitis at baseline showed significantly higher ORs for vonoprazan versus most of the comparator PPIs.
CONCLUSIONS
This analysis shows that the GERD healing effect of vonoprazan is higher than that of rabeprazole (20 mg) but not higher than other PPIs. Subgroup analysis indicated that vonoprazan is more effective than most PPIs for patients with severe erosive esophagitis.
Topics: Bayes Theorem; Esophagitis, Peptic; Gastroesophageal Reflux; Humans; Network Meta-Analysis; Patient Selection; Proton Pump Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Remission Induction; Severity of Illness Index; Sulfonamides; Time Factors; Treatment Outcome; Wound Healing
PubMed: 30883868
DOI: 10.1111/jgh.14664 -
The American Journal of Gastroenterology May 2024Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive... (Meta-Analysis)
Meta-Analysis Comparative Study
INTRODUCTION
Los Angeles grade C/D esophagitis is a severe manifestation of gastroesophageal reflux disease that require active treatment and close follow-up. Potassium competitive acid blockers (P-CAB) are promising alternatives to proton pump inhibitors (PPI). We aimed to compare the efficacy and safety of P-CAB and PPI in healing grade C/D esophagitis to aid clinical decision-making.
METHODS
A systematic literature search was performed using PubMed, MEDLINE, and Cochrane Central Register of Controlled Trials. Randomized controlled trials were eligible for inclusion if efficacy of P-CAB and PPI in healing grade C/D esophagitis was reported. Pooled risk ratios and risk difference with 95% credible intervals were used to summarize estimated effect of each comparison. The benefit of treatments was ranked using the surface under the cumulative probability ranking score.
RESULTS
Of 5,876 articles identified in the database, 24 studies were eligible. Studies included incorporated 3 P-CAB (vonoprazan, tegoprazan, and keverprazan) and 6 PPI (lansoprazole, esomeprazole, omeprazole, rabeprazole extended-release (ER), pantoprazole, and dexlansoprazole). Based on the failure to achieve mucosal healing, 20 mg of vonoprazan q.d. ranked the first among PPI in initial and maintained healing of grade C/D esophagitis (surface under the cumulative probability ranking score = 0.89 and 0.87, respectively). Vonoprazan had similar risk of incurring adverse events, severe adverse events, and withdrawal to drug when compared with PPI. For those who attempted lower maintenance treatment dose, 10 mg of vonoprazan q.d. was a reasonable choice, considering its moderate efficacy and safety.
DISCUSSION
Vonoprazan has considerable efficacy in initial and maintained healing of grade C/D esophagitis compared with PPI, with moderate short-term and long-term safety.
Topics: Humans; Esophagitis; Esophagitis, Peptic; Gastroesophageal Reflux; Network Meta-Analysis; Proton Pump Inhibitors; Pyrroles; Randomized Controlled Trials as Topic; Sulfonamides; Treatment Outcome
PubMed: 38345252
DOI: 10.14309/ajg.0000000000002714 -
Expert Review of Gastroenterology &... May 2023Proton pump inhibitors (PPI) may impact the absorption of vitamin B12. We performed a systematic review to ascertain if PPI use increases risk of vitamin B12 deficiency. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Proton pump inhibitors (PPI) may impact the absorption of vitamin B12. We performed a systematic review to ascertain if PPI use increases risk of vitamin B12 deficiency.
METHODS
Electronic databases (PubMed, Embase, Scopus) were searched on first of September 2022. We selected studies that compared the frequency of vitamin B12 deficiency in PPI users and non-users. Pooled Odds Ratio (OR) was calculated for the occurrence of vitamin B12 deficiency in PPI users compared to non-users. The risk of bias was assessed using the Newcastle Ottawa scale.
RESULTS
Twenty-five studies were included. The pooled OR of vitamin B12 deficiency among PPI users (2852 participants) was higher than non-users (28070 participants) (OR 1.42, 95% CI: 1.16-1.73; I = 54%). Overall risk of PPI use among vitamin B12 deficient individuals was higher than those without deficiency (OR 1.49, 1.20-1.85; I = 68%). Most studies found no difference between serum vitamin B12 levels among PPI users compared to non-users.
CONCLUSION
Although the pooled OR of vitamin B12 deficiency was slightly increased in PPI users, but there was significant heterogeneity, and the pooled OR was too low to imply an association clearly. Better-designed prospective studies in long-term users may clarify the issue.
REGISTRATION
This study was not registered on PROSPERO.
Topics: Humans; Proton Pump Inhibitors; Prospective Studies; Vitamin B 12 Deficiency; Vitamin B 12
PubMed: 37060552
DOI: 10.1080/17474124.2023.2204229 -
Journal of Digestive Diseases Aug 2015We designed this systematic review and meta-analysis aiming to clarify the advantage of steroid therapy compared with non-steroid therapy for the treatment of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We designed this systematic review and meta-analysis aiming to clarify the advantage of steroid therapy compared with non-steroid therapy for the treatment of eosinophilic esophagitis (EoE).
METHODS
PubMed, EMBASE, Medline, ISI Web of Science and the Cochrane Database of Systematic Reviews were searched to identify relevant randomized controlled trials (RCTs) comparing steroid and non-steroid therapy, and retrospective and prospective trials on steroid therapy for EoE. RevMan 5.2 was used for the analysis. Weighted mean difference and 95% confidence interval (CI) were estimated and pooled using meta-analysis methods.
RESULTS
Six RCTs including 193 participants fulfilled the inclusion criteria for meta-analysis, and another two RCTs, three prospective and five retrospective trials were included in systematic review. Meta-analysis showed that topical steroids significantly decreased the mean and peak esophageal eosinophils (EOS) count compared to non-steroid therapy (MDmean = -23.41, 95% CImean -42.08--4.73, P = 0.01 and MDpeak = -51.27, 95% CIpeak -78.62--23.92, P = 0.0002). There were 14 trials showing the efficacy of steroids on decreasing the EOS count, 10 showing the amelioration of symptoms, and five showing endoscopic improvement. Only mild adverse events were reported for topical steroids.
CONCLUSIONS
Steroids are effective on decreasing the EOS count in EoE patients. Its value in ameliorating symptoms and endoscopic changes remains undetermined due to the lack of comparable criteria.
Topics: Eosinophilic Esophagitis; Eosinophils; Glucocorticoids; Humans; Leukocyte Count; Proton Pump Inhibitors
PubMed: 26058809
DOI: 10.1111/1751-2980.12265