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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 -
World Journal of Gastroenterology Nov 2021The use of proton pump inhibitors (PPI) is common worldwide, with reports suggesting that they may be overused. Several studies have found that PPI may affect colorectal...
BACKGROUND
The use of proton pump inhibitors (PPI) is common worldwide, with reports suggesting that they may be overused. Several studies have found that PPI may affect colorectal cancer (CRC) risk.
AIM
To summarize current knowledge on the relationship between PPI and CRC from basic research, epidemiological and clinical studies.
METHODS
This systematic review was based on the patients, interventions, comparisons, outcome models and performed according to PRISMA guidelines. MEDLINE, EMBASE, Scopus, and Web of Science databases were searched from inception until May 17, 2021. The initial search returned 2591 articles, of which, 28 studies met the inclusion criteria for this review. The studies were categorized as basic research studies ( = 12), epidemiological studies ( = 11), and CRC treatment studies ( = 5). The quality of the included studies was assessed using the Newcastle-Ottawa Scale or Cochrane Risk of Bias 2.0 tool depending on the study design.
RESULTS
Data from basic research indicates that PPI do not stimulate CRC development the trophic effect of gastrin but instead may paradoxically inhibit it. These studies also suggest that PPI may have properties beneficial for CRC treatment. PPI appear to have anti-tumor properties (omeprazole, pantoprazole), and are potential T lymphokine-activated killer cell-originated protein kinase inhibitors (pantoprazole, ilaprazole), and chemosensitizing agents (pantoprazole). However, these mechanisms have not been confirmed in human trials. Current epidemiological studies suggest that there is no causal association between PPI use and increased CRC risk. Treatment studies show that concomitant PPI and capecitabine use may reduce the efficacy of chemotherapy resulting in poorer oncological outcomes, while also suggesting that pantoprazole may have a chemosensitizing effect with the fluorouracil, leucovorin, oxaliplatin (FOLFOX) regimen.
CONCLUSION
An unexpected inhibitory effect of PPI on CRC carcinogenesis by way of several potential mechanisms is noted. This review identifies that different PPI agents may have differential effects on CRC treatment, with practical implications. Prospective studies are warranted to delineate this relationship and assess the role of individual PPI agents.
Topics: Capecitabine; Colorectal Neoplasms; Fluorouracil; Humans; Leucovorin; Proton Pump Inhibitors
PubMed: 34908809
DOI: 10.3748/wjg.v27.i44.7716 -
Medicine Nov 2022Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Proton-pump inhibitors (PPIs) and vonoprazan are recommended as first-line therapies for erosive esophagitis (EE). However, it is uncertain how the magnitude of efficacy and safety of first-line therapy, the choice of individual PPIs or vonoprazan in the treatment of EE remains controversial. This study aimed to evaluate the efficacy and safety of vonoprazan and PPIs in healing esophageal mucosal injury in patients with EE.
METHODS
Relevant databases were searched to collect randomized controlled trials of proton pump inhibitors and vonoprazan in the treatment of reflux esophagitis up to December 2021. Studies on standard-dose PPIs or vonoprazan that were published in Chinese or English and assessed healing effects in EE were included in the analysis. Stata16.0 was used to conduct a network Meta-analysis to evaluate the efficacy and safety of the treatment.
RESULTS
A total of 41 literatures were included with 11,592 enrolled patients. For the endoscopic cure rate, all the PPIs and vonoprazan significantly improve compared to Placebo; Based on the surface under the cumulative ranking curve, Ilaprazole ranked first, followed by esomeprazole, vonoprazan, pantoprazole, lansoprazole, omeprazole, rabeprazole and placebo therapy ranked the last. For the rate of adverse events, there was no significant difference among all the PPIs, vonoprazan, and placebo.
CONCLUSIONS
Ilaprazole, esomeprazole and vonoprazan have more advantages in mucosal erosion healing, there was no significant difference in the comparative safety among all interventions.
Topics: Humans; Proton Pump Inhibitors; Esomeprazole; Network Meta-Analysis; Peptic Ulcer; Rabeprazole; Esophagitis, Peptic; Abdominal Injuries
PubMed: 36451489
DOI: 10.1097/MD.0000000000031807 -
PloS One 2014Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although many case reports have described patients with proton pump inhibitor (PPI)-induced hypomagnesemia, the impact of PPI use on hypomagnesemia has not been fully clarified through comparative studies. We aimed to evaluate the association between the use of PPI and the risk of developing hypomagnesemia by conducting a systematic review with meta-analysis.
METHODS
We conducted a systematic search of MEDLINE, EMBASE, and the Cochrane Library using the primary keywords "proton pump," "dexlansoprazole," "esomeprazole," "ilaprazole," "lansoprazole," "omeprazole," "pantoprazole," "rabeprazole," "hypomagnesemia," "hypomagnesaemia," and "magnesium." Studies were included if they evaluated the association between PPI use and hypomagnesemia and reported relative risks or odds ratios or provided data for their estimation. Pooled odds ratios with 95% confidence intervals were calculated using the random effects model. Statistical heterogeneity was assessed with Cochran's Q test and I2 statistics.
RESULTS
Nine studies including 115,455 patients were analyzed. The median Newcastle-Ottawa quality score for the included studies was seven (range, 6-9). Among patients taking PPIs, the median proportion of patients with hypomagnesemia was 27.1% (range, 11.3-55.2%) across all included studies. Among patients not taking PPIs, the median proportion of patients with hypomagnesemia was 18.4% (range, 4.3-52.7%). On meta-analysis, pooled odds ratio for PPI use was found to be 1.775 (95% confidence interval 1.077-2.924). Significant heterogeneity was identified using Cochran's Q test (df = 7, P<0.001, I2 = 98.0%).
CONCLUSIONS
PPI use may increase the risk of hypomagnesemia. However, significant heterogeneity among the included studies prevented us from reaching a definitive conclusion.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Dexlansoprazole; Esomeprazole; Humans; Lansoprazole; Magnesium; Odds Ratio; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Rabeprazole; Risk Factors; Treatment Outcome
PubMed: 25394217
DOI: 10.1371/journal.pone.0112558 -
Medicine Dec 2021Data are conflicting on whether proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel. We investigated individual PPIs and adverse cardiovascular events in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Data are conflicting on whether proton pump inhibitors (PPIs) diminish the efficacy of clopidogrel. We investigated individual PPIs and adverse cardiovascular events in postpercutaneous coronary intervention (PCI) patients on dual antiplatelet therapy with clopidogrel.
METHODS
We searched Ovid-MEDLINE, EMBASE, and Cochrane from inception to March 2020 to identify studies that evaluated the efficacy and safety of clopidogrel added PPIs versus clopidogrel only in post-PCI patient. We extracted data from 28 studies for major adverse cardiovascular endpoints (MACE), myocardial infarction (MI), cardiovascular death, and gastrointestinal bleeding. Risk ratios (RR) and hazard ratios (HR) were pooled separately.
RESULTS
Data were extracted on 131,412 patients from the 28 studies included. Concomitant use of PPI with clopidogrel was associated with increased risk of MACE (RR 1.30; 95% confidence interval [CI] 1.15-1.48; P < .001) and MI (RR 1.43; 95% CI 1.25-1.64; P < .001). Random-effects meta-analyses with individual PPIs demonstrated an increased risk of MACE in those taking pantoprazole (RR 1.31; 95% CI 1.07-1.61, P = .01) or lansoprazole (RR 1.35; 95% CI 1.19-1.54, P < .0001) compared with patients not on PPIs. Likewise, in adjusted analyses, the pooled HR of adjusted events for MACEs showed that the increased risk of MACEs was similar for 4 classes of PPIs but not for rabeprazole (HR: 1.32; 95% CI 0.69-2.53, P = .40).
CONCLUSION
The post-PCI patients on dual antiplatelet therapy with clopidogrel in the PPI group were associated with higher risk of MACE and MI. Although the results for rabeprazole were not robust, it was the only PPI that did not yield a significantly increased risk of MACE.
Topics: Clopidogrel; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Rabeprazole; Ticlopidine; Treatment Outcome
PubMed: 34967346
DOI: 10.1097/MD.0000000000027411 -
Clinical and Experimental Dental... Oct 2022Proton pump inhibitors, such as omeprazole and pantoprazole, are frequently prescribed for the treatment of acid reflux. However, those medications have been shown to... (Review)
Review
OBJECTIVES
Proton pump inhibitors, such as omeprazole and pantoprazole, are frequently prescribed for the treatment of acid reflux. However, those medications have been shown to affect a variety of physiologic processes, including bone homeostasis and the gastrointestinal microbiome. The objective of this study was to assess the relationship between proton pump inhibitors and attachment levels around teeth and dental implants. A scoping review was performed to assess the extent and quality of the relevant literature.
MATERIALS AND METHODS
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) and searched four relevant biomedical literature databases in addition to the grey literature. Keywords in the title and abstract fields, and subject headings for proton pump inhibitors, teeth, and dental implants were included as search terms.
RESULTS
Overall search results identified 791 publications which, after applying the inclusion and exclusion criteria, yielded 27 publications that were further analyzed for relevance and quality of scientific evidence. The majority of eligible publications were retrospective cohort studies. Following critical analysis, 13 publications, including six abstracts, were used to assess the effect of proton pump inhibitors on tissue attachment around teeth and dental implants.
CONCLUSIONS
There are few high-quality studies describing the effect of proton pump inhibitors on tissue attachment around teeth and dental implants. Nevertheless, among the included papers with the fewest confounding factors, there was a positive relationship between proton pump inhibitors and soft tissue attachment levels around teeth, and a predominantly negative but variable effect of proton pump inhibitors on the bone level around dental implants. Additional well-controlled prospective studies are required to fully elucidate those relationships.
Topics: Dental Implants; Humans; Omeprazole; Pantoprazole; Proton Pump Inhibitors; Retrospective Studies
PubMed: 35799099
DOI: 10.1002/cre2.616 -
Gut Pathogens Mar 2021Spontaneous bacterial peritonitis (SBP) is one of the most common infectious diseases in patients with cirrhosis and is associated with serious prognosis. A prevailing...
BACKGROUND
Spontaneous bacterial peritonitis (SBP) is one of the most common infectious diseases in patients with cirrhosis and is associated with serious prognosis. A prevailing dogma posits that SBP is exacerbated by the frequent use of proton pump inhibitors (PPIs).
AIMS
To re-assess the association between PPIs use and SBP incidence with larger and better-quality data.
METHOD
The studies were identified by searching Proquest, Medline, and Embase for English language articles published between January 2008 and March 2020 using the following keywords alone or in combination: anti-ulcer agent, antacid, proton pump inhibitor, proton pumps, PPI, omeprazole, rabeprazole, lansoprazole, pantoprazole, esomeprazole, peritonitis, spontaneous bacterial peritonitis, SBP, ascites, cirrhosis, ascitic and cirrhotic. Three authors critically reviewed all of the studies retrieved and selected those judged to be the most relevant. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was followed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Sub-group analyses were done to decrease the heterogeneity.
RESULTS
A total of twenty-three studies: seven case-control, and sixteen cohorts, involving 10,386 patients were analyzed. The overall results showed a statistically significant association between SBP and PPIs use (pooled odds ratio (OR): 1.80, 95% CI of 1.41 to 2.31). Substantial heterogeneity was observed. On subgroup analysis involving cohort studies, the association was weaker (OR: 1.55 with 95% CI of 1.16 to 2.06 p < 0.00001) but still statistically significant and with high heterogeneity (Chip = 57.68; I = 74%). For case-control studies, the OR was 2.62 with a 95% CI of 1.94 to 3.54. The funnel plot was asymmetric and Egger's test confirmed asymmetry suggesting publication bias (intercept = - 0.05, SE = 0.27, P = 0.850 two-tailed).
CONCLUSION
This meta-analysis sheds light on the conflicting results raised by previous studies regarding the association of SBP with PPIs use. Our meta-analysis showed that there is a weak association, although statistically significant, between SBP and PPIs use. However, the magnitude of the possible association diminished when analysis focused on higher quality data that were more robust. Thus, this updated meta-analysis suggests judicious use of PPIs among cirrhotic patients with ascites.
PubMed: 33741033
DOI: 10.1186/s13099-021-00414-8 -
Frontiers in Pharmacology 2022The cure rates of () treatment using a proton pump inhibitor (PPI) are gradually decreasing due to antibiotic resistance, poor compliance, high gastric acidity, and...
The cure rates of () treatment using a proton pump inhibitor (PPI) are gradually decreasing due to antibiotic resistance, poor compliance, high gastric acidity, and cytochrome P450 2C19 (CYP2C19) polymorphism, and the effects of PPI depend on metabolic enzymes, cytochrome P450 enzymes. The aim of this meta-analysis was to determine whether CYP2C19 polymorphisms affect cure rates in patients treated with different proton pump inhibitors (PPIs) according to stratified analysis. The literature was searched with the key words "" and "CYP2C19" in PubMed, CNKI, and Wanfang up to 31 May 2022, and the studies were limited to clinical observational or randomized controlled trials (RCTs). Finally, seven RCTs and 29 clinical observational studies met the inclusion criteria and were used for the meta-analysis STATA version 16. The cure rates were significantly different between genotypes of homozygous extensive metabolizers (EM) and poor metabolizers (PM) (OR = 0.58, 95% CI: 0.47-0.71) and between EM and heterozygous extensive metabolizers (IM) (OR = 0.71, 95% CI: 0.59-0.86), but not between IM and PM. Moreover, there was a significantly lower cure rate in EM subjects than that in IM subjects when treated with omeprazole (66.4% vs. 84.1%), lansoprazole (76.1% vs. 85.6%), but not rabeprazole, esomeprazole, or pantoprazole. In addition, there was a significantly lower cure rate in EM subjects than that in IM subjects when treated with a PPIs for 7 days (77.4% vs. 82.1%), but not 14 days (85.4% vs. 90.0%). Carriers of CYP2C19 loss-of-function variant alleles (IM and PM) exhibit a significantly greater cure rate of than noncarriers (EM) regardless of other factors (84.7% vs. 79.2%). In addition, pantoprazole- and rabeprazole-based quadruple therapy for treatment is less dependent on the CYP2C19 genotype and should be prioritized in Asian populations with .
PubMed: 36278195
DOI: 10.3389/fphar.2022.938419 -
World Journal of Clinical Cases Oct 2019For a long time, laryngopharyngeal reflux disease (LPRD) has been treated by proton pump inhibitors (PPIs) with an uncertain success rate.
BACKGROUNG
For a long time, laryngopharyngeal reflux disease (LPRD) has been treated by proton pump inhibitors (PPIs) with an uncertain success rate.
AIM
To shed light the current therapeutic strategies used for LPRD in order to analysis the rationale in the LPRD treatment.
METHODS
Three authors conducted a PubMed search to identify papers published between January 1990 and February 2019 about the treatment of LPRD. Clinical prospective or retrospective studies had to explore the impact of medical treatment(s) on the clinical presentation of suspected or confirmed LPRD. The criteria for considering studies for the review were based on the population, intervention, comparison, and outcome framework.
RESULTS
The search identified 1355 relevant papers, of which 76 studies met the inclusion criteria, accounting for 6457 patients. A total of 64 studies consisted of empirical therapeutic trials and 12 were studies where authors formally identified LPRD with pH-monitoring or multichannel intraluminal impedance-pH monitoring (MII-pH). The main therapeutic scheme consisted of once or twice daily PPIs for a duration ranged from 4 to 24 wk. The most used PPIs were omeprazole, esomeprazole, rabeprazole, lansoprazole and pantoprazole with a success rate ranging from 18% to 87%. Other composite treatments have been prescribed including PPIs, alginate, prokinetics, and H Receptor antagonists.
CONCLUSION
Regarding the development of MII-pH and the identification of LPRD subtypes (acid, nonacid, mixed), future studies are needed to improve the LPRD treatment considering all subtypes of reflux.
PubMed: 31624747
DOI: 10.12998/wjcc.v7.i19.2995 -
Journal of the American Heart... Oct 2015Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Observational studies evaluating the possible interaction between proton pump inhibitors (PPIs) and clopidogrel have shown mixed results. We conducted a systematic review comparing the safety of individual PPIs in patients with coronary artery disease taking clopidogrel.
METHODS AND RESULTS
Studies performed from January 1995 to December 2013 were screened for inclusion. Data were extracted, and study quality was graded for 34 potential studies. For those studies in which follow-up period, outcomes, and multivariable adjustment were comparable, meta-analysis was performed.The adjusted odds or hazard ratios for the composite of cardiovascular or all-cause death, myocardial infarction, and stroke at 1 year were reported in 6 observational studies with data on individual PPIs. Random-effects meta-analyses of the 6 studies revealed an increased risk for adverse cardiovascular events for those taking pantoprazole (hazard ratio 1.38; 95% CI 1.12-1.70), lansoprazole (hazard ratio 1.29; 95% CI 1.09-1.52), or esomeprazole (hazard ratio 1.27; 95% CI 1.02-1.58) compared with patients on no PPI. This association was not significant for omeprazole (hazard ratio 1.16; 95% CI 0.93-1.44). Sensitivity analyses for the coronary artery disease population (acute coronary syndrome versus mixed) and exclusion of a single study due to heterogeneity of reported results did not have significant influence on the effect estimates for any PPIs.
CONCLUSIONS
Several frequently used PPIs previously thought to be safe for concomitant use with clopidogrel were associated with greater risk of adverse cardiovascular events. Although the data are observational, they highlight the need for randomized controlled trials to evaluate the safety of concomitant PPI and clopidogrel use in patients with coronary artery disease.
Topics: Clopidogrel; Coronary Artery Disease; Drug Interactions; Drug Therapy, Combination; Humans; Observational Studies as Topic; Odds Ratio; Patient Safety; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Risk Assessment; Risk Factors; Ticlopidine; Treatment Outcome
PubMed: 26514161
DOI: 10.1161/JAHA.115.002245