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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 -
The International Journal of... Aug 2019A comprehensive systematic review on whether proton pump inhibitors (PPIs) are associated with tuberculosis (TB) incidence is lacking. To conduct a systematic review to...
A comprehensive systematic review on whether proton pump inhibitors (PPIs) are associated with tuberculosis (TB) incidence is lacking. To conduct a systematic review to elucidate if there is an association between PPI use and TB risk. We searched the MEDLINE, EMBASE, and Cochrane Library databases from their inception through 14 February 2018. Risk of Bias Assessment tool for Non-randomised Studies (ROBANS) was used to estimate the quality of each study. We could not undertake a meta-analysis because of the small number of studies and the diversity of outcome measures. All results of included studies are described narratively. Five studies were identified. In three case-control studies, compared with non-PPI use, PPI use was associated significantly with TB incidence, a 1.2-to-1.7-fold increased risk (adjusted OR 1.29; 95%CI 1.29-1.30, OR 1.31; 95%CI 1.22-1.41, adjusted hazard ratio 1.71; 95%CI 1.17-2.50). A cohort study reported that ≥3 months of PPI treatment was not associated significantly with TB incidence compared PPI treatment of <3 months. One cohort study reported that lansoprazole use decreased TB development significantly when compared with omeprazole/pantoprazole use. Compared with non-PPI use, PPI use was associated significantly with TB risk but the studies were heterogeneous.
Topics: Humans; Incidence; Proton Pump Inhibitors; Research Design; Risk Factors; Time Factors; Tuberculosis
PubMed: 31533885
DOI: 10.5588/ijtld.18.0585 -
The Turkish Journal of Gastroenterology... May 2019This study aims at evaluating the mean eradication rate by a systematic compilation of the studies which involved the standard triple therapy (STT) in first-line... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
This study aims at evaluating the mean eradication rate by a systematic compilation of the studies which involved the standard triple therapy (STT) in first-line Helicobacter pylori (Hp) eradication in Turkey over a period of 10 years between 2004 and 2013 using the meta-analysis method.
MATERIALS AND METHODS
The systematic compilation and meta-analysis were carried out according to the PRISMA standards defined in the Cochrane handbook. The results of full-text studies published in national and international journals in English and Turkish languages on Turkish population in a period of 10 years, from 2004 to 2013, are included in this study. The studies include open-label trials, controlled trials, treatment arms, and case series that included a triple therapy regimen consisting of standard doses of a proton pump inhibitor (PPI; omeprazole 20 mg BID, lansoprazole 30 mg BID, pantoprazole 40 mg BID, esomeprazole 40 mg BID, or rabeprazole 20 mg BID) along with clarithromycin 500 mg BID and amoxicillin 1 g BID for 7-14 days. They were scanned electronically via the search engines Google Scholar, PubMed, and the Turkish Medicine Index using specific keywords. The related keywords used were Turkey, Helicobacter pylori, infection, standard triple treatment, first-line therapy, eradication, omeprazole, lansoprazole, pantoprazole, rabeprazole, esomeprazole, clarithromycin, and amoxicillin. Studies carried out with adults were included in the evaluation. The publication year of the studies and the included number of patients, their age, gender, treatment duration (7, 10, and 14 days), and PPIs used were evaluated by two separate gastroenterologists and biostatisticians. Studies that used at least one reliable method (histology, urea breath test (UBT), or Helicobacter pylori stool antigen (HpSA) test) four weeks after completing the treatment for the control of Hp eradication were included. Only naive patients were accepted, and patients who had previously received eradication treatment were excluded. The effectiveness of the Hp eradication was analyzed using an intention-to-treat (ITT) or per-protocol (PP) analysis.
RESULTS
The STT regime of 45 studies complying with the inclusion criteria was evaluated. A total of 3715 patients were included in the study. Of the 3010 patients whose gender information was available, 55% were women and 45% were men; the weighted age average given explicitly in the studies was 42.14±0.67. The treatment lasted for 14 days in 42 studies, for 7 days in six studies, and for 10 days in 1 study. The eradication rates evaluated according to the ITT and PP analyses were 60% (95% CI: 56%-63%) and 57% (95% CI: 51%-62%), respectively. The rates for 7 days of treatment were 57% (95% CI: 46%-68%) and 60% (95% CI: 51%-67%) and for 14 days of treatment were 60% (95% CI: 56%-63%) and 56% (95% CI: 50%-62%), respectively. The ITT eradication rate of the only 10-day study was 78% (95% CI: 66%-86%). In the meta-regression analysis, the treatment duration, PPI, age, and gender ratio (women/men) used for the ITT analysis had no effect. The gender ratio and age were not considered in this analysis because they were not clearly stated in studies using the PP analysis. The duration of treatment and the PPI used had no effect.
CONCLUSION
A systematic meta-analysis of studies conducted during the period 2004-2013 in Turkey revealed that the rate of first-line Hp eradication using STT was unacceptably low, and the duration of treatment and PPI used made no difference.
Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Breath Tests; Clarithromycin; Drug Administration Schedule; Drug Therapy, Combination; Female; Helicobacter Infections; Helicobacter pylori; Humans; Male; Proton Pump Inhibitors; Treatment Outcome; Turkey
PubMed: 31060997
DOI: 10.5152/tjg.2019.18693 -
PharmacoEconomics Jun 2011Intravenous esomeprazole (Nexium®) is approved in Europe for the prevention of rebleeding following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers.... (Review)
Review
Intravenous esomeprazole (Nexium®) is approved in Europe for the prevention of rebleeding following therapeutic endoscopy for acute bleeding gastric or duodenal ulcers. In a pivotal clinical trial, patients with peptic ulcer bleeding and high-risk stigmata who received intravenous esomeprazole for 72 hours following endoscopic haemostatic therapy were significantly less likely than those receiving intravenous placebo to experience recurrent peptic ulcer bleeding at days 3, 7 and 30. In addition, the need for repeat endoscopic haemostatic therapy, the total amount of blood transfused and the number of additional hospital days required because of rebleeding were significantly lower in intravenous esomeprazole recipients than in intravenous placebo recipients. All patients received oral esomeprazole for 27 days following intravenous study drug administration. Intravenous esomeprazole was generally well tolerated in the pivotal trial, with infusion-site reactions being among the most commonly reported adverse events. Two pharmacoeconomic analyses conducted from a healthcare payer perspective used decision-tree models with 30-day time horizons to examine the cost effectiveness and cost utility of intravenous esomeprazole in patients with bleeding peptic ulcers who had undergone endoscopic haemostatic therapy. With regard to the incremental cost per bleed averted, intravenous esomeprazole was predicted to be dominant in Spain and cost effective in Sweden and the US compared with no intravenous esomeprazole. Efficacy results and resource utilization data from the pivotal clinical trial were inputted into this model, and the results of the analysis were generally robust to plausible variations in key variables. In the cost-utility analysis, which was conducted in the UK and is available as an abstract and poster, esomeprazole was considered to be the most cost-effective treatment alternative, compared with omeprazole or pantoprazole. For this analysis, clinical outcomes data were obtained from a systematic review and mixed treatment comparison (given the absence of head-to-head trial data), and utility values were proxied from the literature. In conclusion, intravenous esomeprazole prevents peptic ulcer rebleeding in patients who have undergone endoscopic haemostatic therapy. Pharmacoeconomic analyses support the use of intravenous esomeprazole following endoscopic haemostatic therapy in patients with peptic ulcer bleeding and high-risk stigmata.
Topics: Anti-Ulcer Agents; Esomeprazole; Humans; Injections, Intravenous; Omeprazole; Peptic Ulcer Hemorrhage; Secondary Prevention
PubMed: 21568358
DOI: 10.2165/11207430-000000000-00000 -
Drug Safety Feb 2012There is considerable debate regarding the negative impact of concomitant proton pump inhibitor (PPI) therapy on the antiplatelet efficacy of clopidogrel. (Review)
Review
BACKGROUND
There is considerable debate regarding the negative impact of concomitant proton pump inhibitor (PPI) therapy on the antiplatelet efficacy of clopidogrel.
AIM
The aim of this study was to perform a systematic review of studies that have evaluated the platelet function of patients receiving clopidogrel alone compared with those receiving both clopidogrel and PPIs.
METHODS
We searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register in February 2011 for randomized and non-randomized studies that reported platelet function results in patients taking clopidogrel, with or without PPIs.
RESULTS
Our review included 19 studies (13 trials and 6 observational studies) involving 4693 patients. There was considerable heterogeneity in the study designs, patient characteristics, laboratory tests of platelet function, and drug exposure (dose and duration of PPI and clopidogrel). There was some evidence against omeprazole, with five of nine studies demonstrating a significant interaction with clopidogrel. The available platelet function data on esomeprazole (six studies) or pantoprazole (six studies) did not demonstrate a significant interaction. Of the six studies that statistically analysed platelet function data with omeprazole compared with pantoprazole, three showed a significantly greater interaction between omeprazole and clopidogrel, whereas three studies with limited sample sizes were unable to find a significant difference in the effects of omeprazole and pantoprazole.
CONCLUSION
Platelet function studies do not demonstrate a clear or consistent interaction between clopidogrel and PPIs. These studies are difficult to interpret given the lack of information on drug exposure (dose and duration), variation in laboratory methodology and lack of genetic information. Consequently, platelet function data are of uncertain clinical relevance in determining the risk of an adverse cardiovascular interaction between PPIs and clopidogrel. Clinicians should continue to clinically assess the gastrointestinal risk of the patients and make their prescribing decision for PPIs based on any anticipated benefits in reducing risk of peptic ulcers and gastrointestinal haemorrhage.
Topics: Blood Platelets; Clopidogrel; Drug Interactions; Esomeprazole; Humans; Omeprazole; Platelet Aggregation; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Ticlopidine
PubMed: 22204719
DOI: 10.2165/11594900-000000000-00000 -
Frontiers in Pharmacology 2018Short-term use of standard-dose proton pump inhibitors (PPIs) is the first-line initial non-eradication treatment for duodenal ulcer (DU), but the choice on individual...
Standard-Dose Proton Pump Inhibitors in the Initial Non-eradication Treatment of Duodenal Ulcer: Systematic Review, Network Meta-Analysis, and Cost-Effectiveness Analysis.
Short-term use of standard-dose proton pump inhibitors (PPIs) is the first-line initial non-eradication treatment for duodenal ulcer (DU), but the choice on individual PPI drug is still controversial. The purpose of this study is to compare the efficacy, safety, and cost-effectiveness of standard-dose PPI medications in the initial non-eradication treatment of DU. We searched PubMed, Embase, Cochrane Library, Clinicaltrials.gov, China National Knowledge Infrastructure, VIP database, and the Wanfang database from their earliest records to September 2017. Randomized controlled trials (RCTs) evaluating omeprazole (20 mg/day), pantoprazole (40 mg/day), lansoprazole (30 mg/day), rabeprazole (20 mg/day), ilaprazole (10 mg/day), ranitidine (300 mg/day), famotidine (40 mg/day), or placebo for DU were included. The outcomes were 4-week ulcer healing rate (4-UHR) and the incidence of adverse events (AEs). A network meta-analysis (NMA) using a Bayesian random effects model was conducted, and a cost-effectiveness analysis using a decision tree was performed from the payer's perspective over 1 year. A total of 62 RCTs involving 10,339 participants (eight interventions) were included. The NMA showed that all the PPIs significantly increased the 4-UHR compared to H receptor antagonists (HRA) and placebo, while there was no significant difference for 4-UHR among PPIs. As to the incidence of AEs, no significant difference was observed among PPIs, HRA, and placebo during 4-week follow-up. Based on the costs of both PPIs and management of AEs in China, the incremental cost-effectiveness ratio per quality-adjusted life year (in US dollars) for pantoprazole, lansoprazole, rabeprazole, and ilaprazole compared to omeprazole corresponded to $5134.67, $17801.67, $25488.31, and $44572.22, respectively. Although the efficacy and tolerance of different PPIs are similar in the initial non-eradication treatment of DU, pantoprazole (40 mg/day) seems to be the most cost-effective option in China.
PubMed: 30666204
DOI: 10.3389/fphar.2018.01512 -
Pediatrics May 2011Use of proton-pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD) in children has increased enormously. However, effectiveness and safety... (Review)
Review
INTRODUCTION
Use of proton-pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD) in children has increased enormously. However, effectiveness and safety of PPIs for pediatric GERD are under debate.
OBJECTIVES
We performed a systematic review to determine effectiveness and safety of PPIs in children with GERD.
METHODS
We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for randomized controlled trials and crossover studies investigating efficacy and safety of PPIs in children aged 0 to 18 years with GERD for reduction in GERD symptoms, gastric pH, histologic aberrations, and reported adverse events.
RESULTS
Twelve studies were included with data from children aged 0-17 years. For infants, PPIs were more effective in 1 study (compared with hydrolyzed formula), not effective in 2 studies, and equally effective in 2 studies (compared with placebo) for the reduction of GERD symptoms. For children and adolescents, PPIs were equally effective (compared with alginates, ranitidine, or a different PPI dosage). For gastric acidity, in infants and children PPIs were more effective (compared with placebo, alginates, or ranitidine) in 4 studies. For reducing histologic aberrations, PPIs showed no difference (compared with ranitidine or alginates) in 3 studies. Six studies reported no differences in treatment-related adverse events (compared with placebo or a different PPI dosage).
CONCLUSIONS
PPIs are not effective in reducing GERD symptoms in infants. Placebo-controlled trials in older children are lacking. Although PPIs seem to be well tolerated during short-term use, evidence supporting the safety of PPIs is lacking.
Topics: 2-Pyridinylmethylsulfinylbenzimidazoles; Adolescent; Age Factors; Child; Child, Preschool; Cross-Over Studies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gastroesophageal Reflux; Humans; Incidence; Infant; Lansoprazole; Male; Netherlands; Omeprazole; Pantoprazole; Prognosis; Proton Pump Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Treatment Outcome
PubMed: 21464183
DOI: 10.1542/peds.2010-2719 -
Pharmacotherapy Apr 2003Cytochrome P450 (CYP) 2C19 mediates the major metabolic transformations of the proton pump inhibitors (PPIs) omeprazole, pantoprazole, lansoprazole, esomeprazole, and... (Review)
Review
Cytochrome P450 (CYP) 2C19 mediates the major metabolic transformations of the proton pump inhibitors (PPIs) omeprazole, pantoprazole, lansoprazole, esomeprazole, and rabeprazole. Genetic polymorphism of CYP2C19 can lead to significant phenotypic variation in the activity of this isoenzyme and thus in the metabolism of PPIs. We systematically reviewed the pharmacogenetic studies of PPIs with respect to the effects of CYP2C19 polymorphism on the clinical outcomes of PPI therapy. We searched MEDLINE (January 1966-August 2002) and EMBASE (January 1988-August 2002) for English-language articles on the pharmacogenetics of PPIs; the search was supplemented by a bibliographic review of all relevant articles. Seventeen pertinent citations were identified, and the quality (level) of evidence for each was categorized according to the rating scale of the United States Preventive Services Task Force. We found that the relationship between CYP2C19 genetic polymorphism and clinical outcomes after PPI therapy has not yet been clearly delineated. Virtually all pharmacogenetic studies of PPIs have been performed in Japanese men; thus, the clinical relevance of CYP2C19 genetic polymorphism in non-Asian patients and women is unknown. Differences among dual- and triple-therapy drug regimens make it difficult to compare H. pylori eradication studies and assess their applicability to current practice patterns. Drug adherence, a pivotal factor in the success of eradication therapy, was addressed in only four trials. Future directions for research include performing more studies with larger sample sizes, particularly in non-Asian populations and women; measuring plasma PPI concentrations to directly correlate H. pylori infection and ulcer cure rates with plasma drug availability; expanding the study population to patients with gastroesophageal reflux disease; and exploring the influence of CYP3A4 in the success or failure of PPI therapy. Although CYP2C19 genotyping is currently only a research instrument, it may be a valuable clinical tool in select patients to ensure optimal PPI therapy.
Topics: Aryl Hydrocarbon Hydroxylases; Clinical Trials as Topic; Cytochrome P-450 CYP2C19; H(+)-K(+)-Exchanging ATPase; Humans; Mixed Function Oxygenases; Pharmacogenetics; Polymorphism, Genetic; Proton Pump Inhibitors; Proton Pumps
PubMed: 12680476
DOI: 10.1592/phco.23.4.460.32128 -
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