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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 -
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 -
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 -
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 -
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 -
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 -
Clinical Oral Implants Research Oct 2018The aim of this systematic review was to investigate the association between the intake of systemic medications that may affect bone metabolism and their subsequent... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The aim of this systematic review was to investigate the association between the intake of systemic medications that may affect bone metabolism and their subsequent impact on implant failures.
MATERIAL AND METHODS
Electronic and manual literature searches were conducted. Implant failure (IF) was the primary outcome, while biological/mechanical and the causes/timing associated with IF were set as secondary outcomes. Meta-analyses for the binary outcome IF and odds ratio were performed to investigate the association with medications.
RESULTS
A final selection of 17 articles was screened for qualitative assessment. As such, five studies focused on evaluating the association of implant failure and non-steroidal anti-inflammatory drugs (NSAIDs), two on selective serotonin reuptake inhibitors (SSRIs), two on proton pump inhibitors (PPIs), seven on bisphosphonates (BPs), and one on anti-hypertensives (AHTNs). For PPIs, the fixed effect model estimated a difference of IF rates of 4.3%, indicating significantly higher IF rates in the test compared to the control group (p < 0.5). Likewise, for SSRIs, the IF was shown to be significantly higher in the individuals taking SSRIs (p < 0.5) as estimated a difference of 7.5%. No subset meta-analysis could be conducted for AHTNs medications as only one study fulfilled the inclusion criteria, which revealed an increased survival rate of AHTN medication. None of the other medications yielded significance.
CONCLUSIONS
The present systematic review showed an association of PPIs and SSRIs with an increased implant failure rate. Hence, clinicians considering implant therapy should be aware of possible medication-related implant failures.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Bone and Bones; Databases, Factual; Dental Implantation, Endosseous; Dental Implants; Dental Restoration Failure; Diphosphonates; Drug-Related Side Effects and Adverse Reactions; Humans; Pharmaceutical Preparations; Proton Pump Inhibitors; Selective Serotonin Reuptake Inhibitors
PubMed: 30328197
DOI: 10.1111/clr.13137 -
European Journal of Clinical... Sep 2023Proton pump inhibitors (PPIs) reduce acid secretion in the stomach and rank as one of the most widely used acid-suppressing medicines globally. While PPIs are safe in... (Review)
Review
PURPOSE
Proton pump inhibitors (PPIs) reduce acid secretion in the stomach and rank as one of the most widely used acid-suppressing medicines globally. While PPIs are safe in the short-term, emerging evidence shows risks associated with long-term use. Current evidence on global PPI use is scarce. This systematic review aims to evaluate global PPI use in the general population.
METHODS
Ovid MEDLINE, Embase, and International Pharmaceutical Abstracts were systematically searched from inception to 31 March 2023 to identify observational studies on oral PPI use among individuals aged ≥ 18 years. PPI use was classified by demographics and medication factors (dose, duration, and PPI types). The absolute numbers of PPI users for each subcategory were summed and expressed as a percentage.
RESULTS
The search identified data from 28 million PPI users in 23 countries from 65 articles. This review indicated that nearly one-quarter of adults use a PPI. Of those using PPIs, 63% were less than 65 years. 56% of PPI users were female, and "White" ethnicities accounted for 75% of users. Nearly two-thirds of users were on high doses (≥ defined daily dose (DDD)), 25% of users continued PPIs for > 1 year, and 28% of these continued for > 3 years.
CONCLUSION
Given the widespread use PPIs and increasing concern regarding long-term use, this review provides a catalyst to support more rational use, particularly with unnecessary prolonged continuation. Clinicians should review PPI prescriptions regularly and deprescribe when there is no appropriate ongoing indication or evidence of benefit to reduce health harm and treatment cost.
Topics: Adult; Humans; Female; Male; Proton Pump Inhibitors; Upper Gastrointestinal Tract; Health Care Costs; Prescriptions
PubMed: 37420019
DOI: 10.1007/s00228-023-03534-z -
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 -
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