Influence Of Proton Pump Inhibitors Research Articles

THE FOCUS ON INCREASED RISK OF FRACTURES IN THEIR PROLONGED USE

Proton pump inhibitors are the most effective drugs for the treatment of acid-dependent diseases. For a long time, proton pump inhibitors have been considered to be completely safe drugs both for short-term and long-term use. A number of modern clinical studies note that when prescribing proton pump inhibitors in high doses for a long time, the possibility of side effects should be taken into account. The purpose of the review is to study the effect of prolonged use of proton pump inhibitors on the condition of bone tissue and the risk of osteoporotic fractures. Materials and methods. A search was conducted in the PubMed and Scopus information databases for publications on the safety of using proton pump inhibitors, including sources published before December 1, 2023, with an emphasis on the influence of proton pump inhibitors on bone tissue and the possible risk of fractures. Results. According to numerous studies, prolonged use of proton pump inhibitors is associated with an increased risk of fractures of the hip, vertebrae and the wrist. An increased risk of fractures may be associated with hypergastrinemia and hypochlorhydria (due to inhibition of acid secretion by proton pump inhibitors), and electrolyte disorders (hypocalcemia). Conclusions. All the pros and cons of prescribing proton pump inhibitors in patients with a history of fractures associated with osteoporosis should be carefully considered. In the curation of comorbid/multimorbid patients, proton pump inhibitors should be used if medically required for as short duration as possible and at the minimum effective dose to relieve symptoms.

Proton pump inhibitors induced fungal dysbiosis in patients with gastroesophageal reflux disease.

Gut mycobiota inhabits human gastrointestinal lumen and plays a role in human health and disease. We investigated the influence of proton pump inhibitors (PPIs) on gastric mucosal and fecal mycobiota in patients with gastroesophageal reflux diseases (GERD) by using Internal Transcribed Spacer 1 sequencing. A total of 65 participants were included, consisting of the healthy control (HC) group, GERD patients who did not use PPIs (nt-GERD), and GERD patients who used PPIs, which were further divided into short-term (s-PPI) and long-term PPI user (l-PPI) groups based on the duration of PPI use. The alpha diversity and beta diversity of gastric mucosal mycobiota in GERD patients with PPI use were significantly different from HCs, but there were no differences between s-PPI and l-PPI groups. LEfSe analysis identified Candida at the genus level as a biomarker for the s-PPI group when compared to the nt-GERD group. Meanwhile, Candida, Nothojafnea, Rhizodermea, Ambispora, and Saccharicola were more abundant in the l-PPI group than in the nt-GERD group. Furthermore, colonization of Candida in gastric mucosa was significantly increased after PPI treatment. However, there was no significant difference in Candida colonization between patients with endoscopic esophageal mucosal breaks and those without. There were significant differences in the fecal mycobiota composition between HCs and GERD patients regardless whether or not they used PPI. As compared to nt-GERD patient samples, there was a high abundance of Alternaria, Aspergillus, Mycenella, Exserohilum, and Clitopilus in the s-PPI group. In addition, there was a significantly higher abundance of Alternaria, Aspergillus, Podospora, Phallus, and Monographella in the l-PPI group than nt-GERD patients. In conclusion, our study indicates that dysbiosis of mycobiota was presented in GERD patients in both gastric mucosal and fecal mycobiota. PPI treatment may increase the colonization of Candida in the gastric mucosa in GERD patients.

Influence of proton pump inhibitors on the pathological response of rectal cancer: a multicentre study.

The standard neoadjuvant therapy for rectal cancer involves fluoropyrimidines and radiotherapy and, most recently, total neoadjuvant therapy (TNT). A drug-drug interaction between fluoropyrimidines and proton-pump inhibitors (PPI) was suggested, with a negative impact on oncological outcomes in breast, colon and gastric cancers. Little is known about such an effect on rectal tumours. We aimed to evaluate the impact of PPI utilisation on the pathological response after chemoradiation for rectal cancer. Retrospective multicentre study of rectal cancer patients treated with neoadjuvant chemoradiotherapy with capecitabine (cohort 1) or 5-fluororuracil (5-FU) (cohort 2); TNT with oxaliplatin-based regimens was allowed. The pathological response was considered a complete (ypCR) or complete + partial (ypCR + ypPR) according to American Joint Committee on Cancer. PPI use was considered at any time during the neoadjuvant period if concomitant to fluoropyrimidines. From January 2007 to November 2020, 251 patients received capecitabine and 196 5-FU. The rates of PPI use in cohorts 1 and 2 were 20.3% and 26.5%, respectively. TNT was offered to 18.3% in cohort 1. PPI use did not influence ypCR in cohort 1 (yes versus no: 29.4% versus 19.5%; p = 0.13) or 2 (yes versus no: 25.0% versus 26.4%; p = 1.0). Similar ypCR + ypPR were observed in both cohorts 1 (76.5% versus 72.0%; p = 0.60) and 2 (86.5% versus 76.4%; p = 0.16). PPI use was not associated with pathological response in multivariable analysis. PPI users experienced more grade 3 or higher diarrhoea and infections. PPI concomitant to capecitabine/5-FU chemoradiation did not influence the pathological response in rectal cancer but was associated with more treatment-related adverse events.

Do proton pump inhibitors affect the biomechanical efficiency of implant?- a systematic review.

This systematic review was executed to determine the influence of proton pump inhibitors on biomechanical efficiency of dental implants. The comprehensive online literature search was conducted on digital database of Pubmed, Cochrane database and EBSCO host, Web of Science and Scopus from 2010 to 2021(Dec).The studies included in our research comprised of randomized controlled trials and animal studies. Literature review, Letter to the editor, short communication and studies not related to the dental implants were excluded. A total of 6 studies were finalized and included in the systemic review. The proton pump inhibitors have a negative influence on the bone metabolism and adversely affect the Osseointegration of the dental implants. Further they reduce the biomechanical efficiency of dental implant which ultimately results in their failure. Proton pump inhibitors are a risk factor for dental implant survival. This conclusion has been drawn from the limited research available. Hence well designed prospective randomized controlled trials should be carried out on a large population including the users and non-users, to more thoroughly elucidate the effect of proton pump inhibitor on osseointegration process of dental implants.

The influence of proton pump inhibitors on tissue attachment around teeth and dental implants: A scoping review.

ObjectivesProton 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 MethodsWe 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.ResultsOverall 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.ConclusionsThere 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.

Influence of Proton Pump Inhibitors and Histamine Receptor 2 Antagonists on Blastocystis ST3 and Selected Microorganisms of Intestinal Microbiota In Vitro.

INTRODUCTION:Proton pump inhibitors (PPIs) and histamine receptor 2 (H2) antagonists are commonly prescribed medications. Association between PPIs and alteration of the gut microbiota has been reported. Blastocystis, the most common intestinal protozoan worldwide, occurs in both healthy and symptomatic people with gastrointestinal or cutaneous disorders, with controversial pathogenicity. The current study was aimed to investigate the influence of PPIs and H2 blockers on the in vitro proliferation of selected intestinal bacteria, fungi, and protozoa.METHODS:Cultures of Lactobacillus rhamnosus, Escherichia coli, Enterococcus faecium, Candida albicans, and Blastocystis subtype 3 were treated with different concentrations of respective medications in vitro, and the numbers of microorganisms were quantified and compared.RESULTS:Pantoprazole and esomeprazole exerted a significant inhibition on Blastocystis and C. albicans, especially at higher concentrations, which were even more effective than metronidazole. On the other hand, treatment with pantoprazole caused an increase in proliferation of L. rhamnosus and E. coli. There was no influence of H2 blockers on the examined microorganisms.DISCUSSION:PPIs, such as pantoprazole, can be a potential treatment in the prophylaxis or eradication of Blastocystis and C. albicans.

Influence of proton pump inhibitors and H2-receptor antagonists on the efficacy and safety of dasatinib in chronic myeloid leukemia patients.

We evaluated the effect of proton pump inhibitors (PPIs) and H2-receptor antagonists (H2RAs) on the efficacy and safety of dasatinib for chronic-phase chronic myeloid leukemia (CP-CML). Retrospective analyses were performed for patients with CP-CML who received dasatinib at seven hospitals between April 2009 and December 2016. Seventy-three patients were identified, 16 of whom received PPIs or H2RAs concurrently with dasatinib. Major molecular response at 12months was observed in 13 of 13 patients (100%) with concurrent PPIs or H2RAs (combination group), and in 23 of 51 patients (45.1%) who received only dasatinib (dasatinib-alone group; P < 0.001). Deep molecular response at 12months was observed in four of six patients (66.7%) in the combination group, and seven of 38 patients (18.4%) in the dasatinib-alone group (P = 0.027). Dasatinib chemotherapy was stopped after 18months for 25 patients (43.9%) from the dasatinib-alone group, but for none from the combination group. Combination treatment with PPIs or H2RAs did not reduce the efficacy of dasatinib. PPIs and H2RAs reduce the incidence of dasatinib discontinuation due to adverse events and increase the efficacy of dasatinib chemotherapy for patients.

Comparative analysis of the risk of osteoporotic fractures with proton pump inhibitor use and histamine-2 receptor antagonist therapy in elderly women: A nationwide population-based nested case-control study.

The influence of proton pump inhibitors (PPIs) on the risk of osteoporotic fractures remains to be elucidated, especially in the Asian population. This study evaluated the risk of osteoporotic fractures in elderly female Korean PPI users compared to histamine-2 receptor antagonist (H2RA) users, as well as the relationship between fractures and the duration, dose, and pattern of use of PPI. We screened a nationwide cohort of elderly Korean women who underwent bone mineral density measurements during their 66-year-old life-transition medical examination between 2009 and 2014. Study subjects included 8903 cases diagnosed with new osteoporotic fractures and 44,515 matched controls (1:5 ratio based on cohort entry date, follow-up duration, and baseline osteoporosis status) without fractures. They were followed up until 2015. Information on the exposure to PPI or H2RA, occurrence of fracture, and covariates were obtained from the Korean National Health Insurance Service data. Covariate-adjusted odds ratio (aOR) and 95% confidence interval (CI) were estimated using conditional logistic regression analysis. PPI use was associated with an increased risk of osteoporotic fractures (aOR: 1.13, 95% CI: 1.07, 1.18) compared with H2RA-only use. Increasing duration of PPI use was positively associated with the risk of osteoporotic fracture [aOR (95% CI) of long-term PPI use (≥1year): 1.3 (1.09, 1.56)]. Recent PPI use within the last year was associated with an increased risk of fracture (aOR: 1.31, 95% CI: 1.23, 1.38), whereas remote PPI use was not (aOR: 0.98, 95% CI: 0.92, 1.04). The risk of fracture did not increase with the increasing cumulative PPI dose. Compared with the use of H2RA alone, PPI use was associated with an increased risk of osteoporotic fractures in elderly Korean women, particularly among those who had used PPI within the last year or for more than one year.

Long-term use of proton pump inhibitors does not affect ectopic and metachronous recurrence of gastric cancer after endoscopic treatment

Objective: Long-term administration of proton pump inhibitors (PPIs) after eradication of Helicobacter pylori infection has been reported to increase the risk for development of gastric cancer (GC). We investigated whether long-term administration of PPI affects ectopic and metachronous recurrence of GC after endoscopic treatment.Methods: Participants were 687 patients who underwent endoscopic treatment for GC from January 2005 to March 2018. Questionnaire surveys and medical record reviews of medications, including PPIs, H2 receptor antagonists and low-dose aspirin (LDA) were conducted for all patients. The influence of PPI in ectopic and metachronous recurrence of GC was evaluated with Cox’s proportional hazard analysis.Results: Patients who did not respond to the questionnaire and those who underwent additional treatment after endoscopic treatment were excluded from analyses; 418 patients were included. During an average observation period of 1608 days (range, 375–4993 days), 136 patients (32.5%) took PPIs for more than 1 year and 94 took PPIs for more than 3 years; of those, 40 had ectopic and metachronous recurrences. Cox’s proportional hazards analysis revealed that long-term use of PPIs (for both 1 year and 3 years) was not a risk factor for recurrence. In addition, age, severity of gastric atrophy, long-term use of LDA, current infection with H. pylori, and cure achieved with the first endoscopic treatment were also not risk factors for recurrence.Conclusions: Long-term use of PPIs does not affect ectopic and metachronous recurrence of GC after endoscopic treatment.

Proton pump inhibitors and risk for recurrent ischemic events or death in outpatients with symptomatic artery disease

Bagkground and aimsThe influence of proton pump inhibitors (PPIs) on outcome in patients with symptomatic artery disease remains controversial. MethodsFRENA is a prospective registry of consecutive outpatients with symptomatic coronary (CAD), cerebrovascular (CVD) or peripheral artery disease (PAD). We compared the risk for subsequent ischemic events or death according to the use of PPIs. ResultsAs of December 2016, 5170 patients were recruited: 1793 (35%) had CAD, 1530 (30%) CVD and 1847 (35%) had PAD. Overall, 2289 patients (44%) were regularly using PPIs. During a median follow-up of 36 months, 172 patients suffered a recurrent myocardial infarction, 139 had ischemic stroke, 71 underwent limb amputation and 267 died (cardiovascular death, 109). On multivariable analysis, patients using PPIs were at a lower risk for subsequent limb amputation (hazard ratio [HR]: 0.53; 95%CI: 0.30–0.94), a similar risk for myocardial infarction (HR: 0.78; 95%CI: 0.55–1.10) or stroke (HR: 0.93; 95%CI: 0.64–1.35) and at a higher risk of death (HR: 1.37; 95%CI: 1.04–1.79). ConclusionsAmong stable outpatients with symptomatic artery disease, the use of PPIs was associated with a lower risk for subsequent ischemic events but a higher risk for death.

Prevention of gastric cancer by Helicobacter pylori eradication: A review from Japan.

Japan introduced a Helicobacter pylori eradication therapy strategy in 2013, with the aim of decreasing the number of gastric cancer‐related death, the number of new cases of gastric cancer, and associated medical costs. Five years have passed since then, but no reduction in the annual number of gastric cancer has been observed. In addition, it was suggested that the number of deaths due to gastric cancer could be reduced to 30,000 a year by 2020, but the annual death toll in 2017 remained at more than 45,000. Based on the above evidence, it was examined whether it was possible to reach the target value based on the data from the last 5 years. The number of deaths per year in 2020 is predicted to be more than 40,000, which is clearly different from the target value. Logically, the effect of the strategy might appear by 2023. However, there is a possibility that the risk of gastric cancer may increase in some populations due to the influence of proton pump inhibitors and dysbiosis in the gastric microbiome. To solve these problems, combined therapy with PPIs and aspirin for patients after H pylori eradication should be considered.

Influence of proton pump inhibitors on microbiota in chronic liver disease patients.

Current knowledge suggests that proton pump inhibitors (PPIs) are associated with an increased risk of hepatic encephalopathy (HE) and spontaneous bacterial peritonitis (SBP). These conditions and PPI use are related to gut microbiota. The aim of this study is to research the changes in gut microbiota caused by PPI in patients with chronic liver disease. From 198 Japanese patients, 31 patients in the PPI and non-PPI groups were matched using propensity score matching (PSM) based on age, sex, and Child-Turcotte-Pugh class. We investigated the gut microbial composition of stool samples using the Illumina MiSeq sequencing platform and compared them using linear discriminant analysis effect size and phylogenetic investigation of communities by reconstruction of unobserved states. Before PSM, Child-Turcotte-Pugh score (p = 0.038), ascites (p = 0.049), encephalopathy (p = 0.023), and esophageal varices (p < 0.01) were significantly higher in the PPI group than in the non-PPI group. After PSM, six genera, consisting of Lactobacillus, Streptococcus, Selenomonas, Veillonella, Campylobacter, and Haemophilus were enriched in the PPI group. Eggerthella, Paraprevotella, Turicibacter, Dorea, Anaerotruncus, and Ruminococcus were less abundant in the PPI group. We identified five types of level 3 KEGG pathways predicted to be significantly different. Part of microbial changes caused by PPI use was common to the changes by progression of liver cirrhosis. Increases in oral bacterial flora and decreases in autochthonous flora may produce the intestinal environment which tends to make the risk factor for HE or SBP.

Влияние ингибиторов протонной помпы на когнитивные функции и риск деменции

Влияние ингибиторов протонной помпы на когнитивные функции и риск деменции

Commentary: The Influence of Proton Pump Inhibitors on the Fecal Microbiome of Infants with Gastroesophageal Reflux-A Prospective Longitudinal Interventional Study.

Commentary: The Influence of Proton Pump Inhibitors on the Fecal Microbiome of Infants with Gastroesophageal Reflux-A Prospective Longitudinal Interventional Study.

Lower Trabecular Bone Score is Associated With the Use of Proton Pump Inhibitors

Introduction: Trabecular bone score (TBS) provides indirect indices of trabecular microarchitecture and bone quality. Several studies have evaluated the influence of proton pump inhibitors (PPIs) on bone mass and geometric parameters, but no studies have evaluated the influence of PPIs on TBS. Methods: We reviewed the medical records of 1505 women aged 40–89 yr who had bone mineral density (BMD) examinations as a part of the medical diagnosis and disease prevention program and who did not have osteoporotic fractures or conditions that could affect bone metabolism. Among these, we identified 223 women with exposure to PPIs and selected the same number of age- and body mass index (BMI)-matched control patients. We compared TBS and BMD between the PPI exposure group and the control group and performed multivariate regression analyses to determine whether TBS and BMDs are associated with age, BMI, and PPIs exposure. We also examined whether TBS and BMDs are associated with PPIs exposure timing (current, recent, and past). Results: TBS and BMDs were significantly lower in the PPI exposure group than in the control group. In a multivariable linear regression analysis, TBS was significantly associated with age (p < 0.001) and PPI exposure (p = 0.02). In addition, all BMDs were found to be significantly associated with age, BMI, and PPI exposure. Lower TBS was associated with current PPIs use (p = 0.005), but not with recent or past PPIs usage. However, the influence of PPI exposure timing on the BMDs was not consistent between BMD measurement sites. Conclusions: This study found that TBS is lower in subjects with PPIs exposure than in controls. The association of lower TBS with current PPIs use suggests that trabecular bone quality could be affected early by PPIs, and but the effect might be reversible.

Influence of proton pump inhibitors on clinical outcomes in coronary heart disease patients receiving aspirin and clopidogrel

Background:Proton pump inhibitors (PPIs) are usually prescribed to protect against gastrointestinal bleeding in patients on dual antiplatelet therapy. This meta-analysis reviewed clinical outcomes in patients taking aspirin and clopidogrel, with and without concomitant PPIs to address concerns of adverse reactions.Methods:We searched PubMed, Embase, and the Cochrane Library for articles published between January 1, 2010 and April 11, 2017. The primary end points were major adverse cardiovascular events and gastrointestinal bleeding. Secondary end points were myocardial infarction, stent thrombosis, revascularization, cardiogenic death, and all-cause mortality.Results:The meta-analysis included 33,492 patients in 4 randomized controlled trials and 8 controlled observational studies. Overall, patients taking PPIs had statistical differences in major adverse cardiovascular events [odds ratio (OR) 1.17 (95% confidence interval [CI] 1.07–1.28); P = .001; I2 = 28.3%], gastrointestinal bleeding [OR 0.58 (95% CI 0.36–0.92); P = .022; I2 = 80.6%], stent thrombosis [OR 1.30 (95% CI 1.01–1.68); P = .041; I2 = 0%], and revascularization [OR 1.20 (95% CI 1.04–1.38); P = .011; I2 = 5.1%], compared those not taking PPIs. There were no significant differences in myocardial infarction [OR 1.03 (95% CI 0.87–1.22); P = .742; I2 = 0%], cardiogenic death [OR 1.09 (95% CI 0.83–1.43); P = .526; I2 = 0%], or all-cause mortality [OR 1.08 (95% CI 0.93–1.25); P = .329; I2 = 0%).Conclusions:Among the patients taking aspirin and clopidogrel, the results indicated that the combined use of PPIs increased the rates of major adverse cardiovascular events, stent thrombosis, and revascularization.

Validation of In Vivo Vertebral Fracture Assessment Using the Norland Illuminatus Software

Introduction: Trabecular bone score (TBS) provides indirect indices of trabecular microarchitecture and bone quality. Several studies have evaluated the influence of proton pump inhibitors (PPIs) on bone mass and geometric parameters, but no studies have evaluated the influence of PPIs on TBS. Methods: We reviewed the medical records of 1505 women aged 40–89 yr who had bone mineral density (BMD) examinations as a part of the medical diagnosis and disease prevention program and who did not have osteoporotic fractures or conditions that could affect bone metabolism. Among these, we identified 223 women with exposure to PPIs and selected the same number of age- and body mass index (BMI)-matched control patients. We compared TBS and BMD between the PPI exposure group and the control group and performed multivariate regression analyses to determine whether TBS and BMDs are associated with age, BMI, and PPIs exposure. We also examined whether TBS and BMDs are associated with PPIs exposure timing (current, recent, and past). Results: TBS and BMDs were significantly lower in the PPI exposure group than in the control group. In a multivariable linear regression analysis, TBS was significantly associated with age (p < 0.001) and PPI exposure (p = 0.02). In addition, all BMDs were found to be significantly associated with age, BMI, and PPI exposure. Lower TBS was associated with current PPIs use (p = 0.005), but not with recent or past PPIs usage. However, the influence of PPI exposure timing on the BMDs was not consistent between BMD measurement sites. Conclusions: This study found that TBS is lower in subjects with PPIs exposure than in controls. The association of lower TBS with current PPIs use suggests that trabecular bone quality could be affected early by PPIs, and but the effect might be reversible.

Reduced susceptibility of Enterococcus spp. isolates from Cairo University Hospital to tigecycline: Highlight on the influence of proton pump inhibitors.

The incidence of reduced susceptibility to tigecycline (TIG) is increasing. This study aimed to analyse the in vitro activity of TIG against Enterococcus spp. isolates recovered from hospitalised patients and to evaluate the effect of omeprazole on the in vitro antimicrobial activity of TIG against several enterococcal species. A total of 67 Enterococcus clinical isolates were identified by MALDI-TOF/MS and multiplex PCR. Minimum inhibitory concentrations (MICs) of TIG alone and in combination with omeprazole (10, 30 and 60mg/L) were determined by broth microdilution. Antibiotic susceptibility to other antibiotics was determined by disk diffusion. The presence of van, tet(X) and tet(X1) genes was tested by multiplex PCR. Of the 67 Enterococcus isolates, 2 (3.0%) were resistant to TIG and 13 (19.4%) were intermediate-resistant according to EUCAST. The frequencies of resistance to norfloxacin (80.6%), doxycycline (80.6%), levofloxacin (74.6%) and ciprofloxacin (71.6%) were highest, whilst that of vancomycin (25.4%) was lowest. The vanA gene was detected in 11 Enterococcus isolates (8 Enterococcus faecalis, 3 Enterococcus faecium), vanB in 3 Enterococcus isolates (2 E. faecium, 1 E. faecalis) and vanC-2/3 in 3 Enterococcus casseliflavus. Nine isolates (13.4%) were positive for tet(X1). TIG resistance occurred both in patients receiving or not TIG and/or omeprazole. Omeprazole increased TIG MICs by 4-128-fold. The possibility of selection of TIG-non-susceptible Enterococcus in the gut may occur with long-term use of omeprazole. Omeprazole influenced TIG activity in a concentration-dependent manner. To our knowledge; this is the first report of TIG-non-susceptible Enterococcus spp. in Egypt.

Influence of proton pump inhibitors in the development of spontaneous bacterial peritonitis.

AIMTo investigate whether the use of proton pump inhibitors (PPIs) increases the incidence of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis and ascites.METHODSAn historical cohort study was carried out in cirrhotic outpatients with ascites followed in a specialized clinic at a tertiary hospital in Southern Brazil. Patient charts were reviewed to collect information on the variables of interest as the use of PPIs. Primary outcome was defined as development of SBP during the study period. SBP was diagnosed based on ascitic fluid polymorphonuclear cell count ≥ 250 cells/mm³ without evidence of an intra-abdominal, surgically treatable source of infection.RESULTSOf 738 cirrhotic patients, 582 (58.2% male) were enrolled, with mean age of 53.6 ± 12 years. Hepatitis C virus infection (36.2%) and alcohol abuse (25.6%) were the main etiologies of cirrhosis. The presence of ascites was detected in 299 (51.4%) patients during the development of the study. Nineteen patients with previous diagnosis of SBP undergoing secondary prophylaxis and 22 patients with insufficient PPI data were further excluded. Of 258 patients with ascites, 151 used PPIs, and 34 developed SBP (22.5%). Among 107 non-users of PPIs, 23 developed SBP (21.5%) (HR = 1.44, 95%CI: 0.85-2.47, P = 0.176). The median follow-up time of patients using PPI was 27 mo vs 32 mo for non-users. Univariate analysis of the risk factors associated with the development of SBP revealed a significant association of SPB with the severity of liver disease according to the Child-Turcotte-Pugh (CTP) score. Multivariate analysis confirmed that CTP score was the only independent variable influencing the occurrence of SBP. Survival at 60 mo (Kaplan-Meier analysis) was similar in users and non-users of PPI, independently of the presence of SBP (58.4% vs 62.7% respectively, P = 0.66). For patients with SBP, survival at 60 mo was 55.1%, vs 61.7% in patients without SBP (P = 0.34).CONCLUSIONIn conclusion, the rate of SBP was not significantly different in users or non-users of PPIs in this cohort of cirrhotic with ascites.

Influence of proton pump inhibitors on blood dabigatran concentrations in Japanese patients with non-valvular atrial fibrillation

BackgroundDabigatran is a direct thrombin inhibitor used to decrease the risk of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Its prodrug, dabigatran etexilate (DE) is often co-administrated with a proton pump inhibitor (PPI) because of its adverse effects on the gastrointestinal tract. Drug-drug interactions between DE and PPIs in daily clinical practice have not been fully elucidated. MethodsChanges in blood dabigatran concentration (DC) were investigated using the dilute thrombin time test in a randomized, open-label, two-period crossover study including 34 Japanese patients with NVAF receiving dabigatran therapy with or without PPI. ResultsThe average trough DC was significantly higher without PPI than with PPI (83 ± 42.3 vs. 55.5 ± 24.6 ng/mL, respectively; P < 0.001). Similarly, the average peak DC was significantly higher without PPI than with PPI (184.1 ± 107.7 vs. 124 ± 59.2 ng/mL, respectively; P = 0.0029). The average ratio of DC change at the trough and peak levels did not differ significantly among the three PPI types. ConclusionsPPI administration significantly decreased the trough and peak DCs in patients with NVAF. Therefore, when prescribing PPIs for patients with NVAF in a clinical setting, the possibility that the bioavailability of dabigatran may decrease should be considered.