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Objectives: Beta-blockers and endoscopic variceal band ligation (VBL) have been preferred therapies for primary prophylaxis of variceal bleeding. However, the choice of therapy in patients with advanced liver disease with high-risk varices is not clear. A comparison of these therapies alone or in combination to prevent the first variceal bleed in advanced cirrhosis patients was carried out., Design: 330 Child-Turcotte-Pugh (CTP) B and C cirrhosis patients, with 'high-risk' varices were prospectively enrolled (n=110 per group) to receive carvedilol (group A), VBL (group B) or combination (group C). Primary endpoint was reduction in the incidence of first variceal bleed at 12 months. The secondary endpoints included overall mortality, bleed-related mortality, new-onset decompensation, change in hepatic vein pressure gradient (HVPG) and treatment-related adverse events., Results: The patients were predominantly males (85.2%), aged 51.4±10.5 years with CTP score of 8.87±1.24, MELD score 15.17±3.35 and HVPG-16.96±3.57 mm Hg. The overall incidence of variceal bleed was 23.8% (n=78) at 1 year. Intention-to-treat analysis showed that the combination arm (group C) significantly reduced the incidence of first variceal bleed by 62.9% as compared with group B (HR 0.37, 95% CI 0.192 to 0.716, p<0.003) and by 69.3% as compared with group A (HR 0.31, 95% CI 0.163 to 0.578, <0.001). The overall mortality was 13.6% (45/330). The 1-year mortality in group C was lowest among the three groups (A, B, C=20%, 14.5%, 6.3%, p=0.012). Reduction in HVPG (20.8% vs 25.1%, p=0.54) and the rate of non-response to carvedilol (53.4% vs 41.25%, p=0.154) were not different between group A and C patients. The incidence of new-onset ascites, spontaneous bacterial peritonitis, shock, and acute kidney injury and postbleed organ failure was also comparable between the groups., Conclusion: In CTP B and C cirrhosis patients with high-risk varices, combination of carvedilol and VBL is more effective than either therapy alone, for primary prevention of variceal bleeding., Trial Registration Number: NCT03069339., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The purpose of this study was to investigate the efficacy and safety of endoscopic ultrasound (EUS)-guided injection of cyanoacrylate (CYA) and transjugular intrahepatic portal shunts (TIPSs) in the treatment of patients with cirrhosis with ruptured gastric varices., Methods: In this retrospective study, 105 patients with liver cirrhosis and gastric varicose veins who were admitted to the First Affiliated Hospital of Anhui Medical University between April 2018 and April 2023 without nonselective β-blockers treatment and no portal vein thrombosis were evaluated. The patients were divided into the transjugular intrahepatic portal shunt (TIPS) group (n = 60) and the EUS-CYA group (n = 45) for the purpose of evaluating postoperative rebleeding rates, complications, survival rates, and other factors., Results: During the follow-up, there was no significant difference in the rebleeding rates between the TIPS group and EUS-CYA group within 3 months (5% vs 2.2%; P = 0.825; 10% vs 20%, P = 0.147). However, the TIPS group had significantly lower rebleeding rates than the EUS-CYA group at 6 months (10% vs 33.3%; P = 0.030) and 1 year or longer (11.7% vs 42.2%; P < 0.01). In terms of hepatic encephalopathy, the incidence rate of the TIPS group was significantly higher than that of the EUS-CYA group (20% vs 2.2%; P = 0.006). In addition, there was no difference in the survival rates between the two groups (93.3% vs 97.8%; P = 0.552)., Conclusions: TIPS is superior to EUS in preventing rebleeding in patients with ruptured varices of the fundus, but it has a higher incidence of hepatic encephalopathy, and there is no difference in long-term survival between the two groups., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Antithrombotic agents, including antiplatelet agents and anticoagulants, are widely used in Korea because of the increasing incidence of cardiocerebrovascular disease and the aging population. The management of patients using antithrombotic agents during endoscopic procedures is an important clinical challenge. The clinical practice guidelines for this issue, developed by the Korean Society of Gastrointestinal Endoscopy, were published in 2020. However, new evidence on the use of dual antiplatelet therapy and direct anticoagulant management has emerged, and revised guidelines have been issued in the United States and Europe. Accordingly, the previous guidelines were revised. Cardiologists were part of the group that developed the guideline, and the recommendations went through a consensus-reaching process among international experts. This guideline presents 14 recommendations made based on the Grading of Recommendations, Assessment, Development, and Evaluation methodology and was reviewed by multidisciplinary experts. These guidelines provide useful information that can assist endoscopists in the management of patients receiving antithrombotic agents who require diagnostic and elective therapeutic endoscopy. It will be revised as necessary to cover changes in technology, evidence, or other aspects of clinical practice.

Background/aims: The incidence of acute gastrointestinal bleeding (GIB) increases with the utilization of anticoagulant and nonsteroidal anti-inflammatory drugs (NSAIDs). This study aimed to compare the risk of GIB between anticoagulant and NSAIDs combotherapy and anticoagulant monotherapy in real-world practice., Methods: We investigated the relative risk of GIB in individuals newly prescribed anticoagulant and NSAIDs combination therapy and that in individuals newly prescribed anticoagulant monotherapy at three hospitals using "common data model." Cox proportional hazard models and Kaplan-Meier estimation were employed for risk comparison after propensity score matching., Results: A comprehensive analysis of 2,951 matched pairs showed that patients who received anticoagulant and NSAIDs combousers exhibited a significantly higher risk of GIB than those who received anticoagulant monousers (hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.30 to 2.12; p<0.001). The risk of GIB associated with anticoagulant and NSAIDs combination therapy was also significantly higher than that associated with anticoagulant monotherapy in patients aged >65 years (HR, 1.53; 95% CI, 1.15 to 2.03; p=0.003) and >75 years (HR, 1.89; 95% CI, 1.23 to 2.90; p=0.003). We also found that the risk of GIB was significantly higher in the patients who received anticoagulant and NSAIDs combousers than that in patients who received anticoagulant monousers in both male (p=0.016) and female cohorts (p=0.010)., Conclusions: The risk of GIB is significantly higher in patients who receive anticoagulant and NSAIDs combotherapy than that in patients who receive anticoagulant monotherapy. In addition, the risk of GIB associated with anticoagulant and NSAIDs combotherapy was much higher in individuals aged >75 years. Therefore, physicians should be more aware of pay more attention to the risk of GIB when they prescribe anticoagulant and NSAIDs.

Introduction: Patients on systemic oral anticoagulation with vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOAC) often require triple therapy following percutaneous coronary intervention, substantially increasing the risk of bleeding. Gastroprotective agents like proton pump inhibitors (PPI) are often employed to mitigate this risk, despite potential competitive inhibition between P2Y12-receptor inhibitors, NOACs, and VKAs. While the interactions and clinical outcomes of PPIs and DAPT have been frequently explored in literature, not many studies have evaluated the same outcomes for triple therapy., Areas Covered: This comprehensive narrative review of three studies on PPIs and triple from the PubMed/MEDLINE database supplemented by 23 other relevant studies aims to use the available literature to analyze the potential interactions between PPIs and triple therapy while shedding light on their mechanisms, clinical implications, and areas for optimization., Expert Opinion: If triple therapy is indicated following PCI, then patients at high-risk for bleeding may benefit from transition to apixaban and a PPI to lower the risk of gastrointestinal bleeding. More research is needed to determine the role of PPIs in triple therapies in prevention of gastrointestinal bleeding or potentiation of other adverse outcomes.

Transjugular intrahepatic portosystemic shunt (TIPS) has become essential in the treatment or prevention of portal hypertension-related complications. In the early 1990s, the primary indication was refractory bleeding. It is now proposed for the treatment of ascites for the prevention of bleeding and in patients with vascular diseases of the liver. Thus, there are a growing number of patients being treated with TIPS all over the world. The broadening of indications, the involvement of multiple stakeholders, the need for an accurate selection, the positioning in relation to transplantation and the lack of standardization in pre-therapeutic assessment, in the procedure itself and in the follow-up have led the board of the French Association for the Study of the Liver to establish recommendations., (© 2024 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: Guidelines provide various recommendations for the use of proton pump inhibitors (PPI) to prevent upper gastrointestinal (UGI) bleeding in acute myocardial infarction (MI) treatment with dual antiplatelet therapy (DAPT). We evaluated the effects of PPIs in reducing the risk of severe UGI bleeding in patients with MI receiving DAPT., Methods: This retrospective cohort study included patients admitted for acute MI between 2014 and 2018, based on a nationwide health claims database in Korea. Primary outcome was admission for severe UGI bleeding requiring transfusion within 1 year of MI diagnosis. A multivariable Cox regression model was used to calculate the association between PPI use and severe UGI bleeding risk., Results: Of 100,556 patients with MI on DAPT (mean age, 63.7 years; 75.4% men), 37% were prescribed PPIs. Based on risk assessment for UGI bleeding, among 6,392 (6.4%) high-risk and 94,164 (93.6%) low-risk patients, 50.5% and 35.8% received PPIs, respectively. Overall, 0.5% of the patients experienced severe UGI bleeding within 1 year after MI. The use of PPI was associated with a reduced risk of severe UGI bleeding (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.47-0.70; P < 0.001). The benefits of PPIs were consistent in high-risk (HR, 0.71; 95% CI, 0.45-1.13; P = 0.147) and low-risk (HR, 0.54; 95% CI, 0.43-0.68; P < 0.001) patients (P for interaction = 0.481)., Conclusions: Among Korean patients with MI receiving DAPT, PPIs were underutilized, even among those at high risk of severe UGI bleeding. Nonetheless, PPI use reduced severe UGI bleeding in low- and high-risk groups., (© 2024. The Author(s).)

Antisecretory medications, primarily proton pump inhibitors (PPIs), have proven effective in reducing upper gastrointestinal toxicities, including upper gastrointestinal bleeding (UGIB), associated with nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin, which are among the most commonly used medications in the United States. 1 Accordingly, professional guidance recommends PPIs for patients at high risk for UGIB. 2-4 However, little is known about trends in use of antisecretory medications for gastrointestinal prophylaxis ("gastroprotection"). Herein, we examined contemporary use and prescribing of antisecretory medications in visits by patients at high risk for UGIB, relative to visits by patients diagnosed with acid-related disorders., (Published by Elsevier Inc.)

Purpose of Review: This review explores the pharmacokinetics, benefits, and risks of proton pump inhibitors (PPIs) in cirrhotic patients, focusing on the appropriateness of their use and potential adverse effects., Recent Findings: Recent studies highlight significant pharmacokinetic alterations in PPIs among cirrhotic patients, with marked increases in lansoprazole and pantoprazole exposure and relatively stable levels of esomeprazole. While effective for managing acid-related disorders and post-band ulcer rebleeding, evidence supporting PPI use for portal hypertension-related bleeding is lacking. Emerging research suggests potential adverse effects such as hepatic decompensation, spontaneous bacterial peritonitis, hepatic encephalopathy, and increased mortality, possibly linked to dysbiosis and bacterial translocation. PPI use in cirrhotic patients alters pharmacokinetics significantly, with esomeprazole potentially safer in advanced cirrhosis. The review advises caution in routine PPI use beyond acid-related conditions due to limited evidence and substantial risks. It underscores the need for careful risk-benefit assessments and exploration of alternative therapies. Future research should aim to identify safer management strategies for portal hypertension complications and to develop evidence-based guidelines for PPI use in patients with cirrhosis., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This narrative review summarizes the current body of literature regarding periprocedural management of direct oral anticoagulant (DOAC)-treated patients undergoing digestive endoscopy since the publication of the 2022 American College of Gastroenterology - Canadian Association of Gastroenterology guidelines. We provide a detailed analysis of the thromboembolic risk, endoscopic procedure-specific bleeding risks, contemporary intraprocedural techniques to reduce the bleeding risk, and a summary of periprocedural DOAC guidelines developed by major gastrointestinal societies, including recommendations on procedure risk stratification. Despite data heterogeneity, the overall trend of the current literature supports the contemporary practice of a minimal DOAC interruption without the need for heparin bridging.

Objectives: The application of rifaximin, a non-absorbable antibiotic, in hepatic encephalopathy (HE) has been well established; however, its effect on other complications in cirrhotic patients with previous gastroesophageal variceal bleeding (GEVB) remains unclear. Therefore, we performed a pilot randomized controlled trial aiming to evaluate the impact of rifaximin on cirrhosis-related complications and changes in gastric microbiota., Methods: Eighty cirrhotic patients who received prophylactic endoscopic treatment for variceal rebleeding were randomly assigned to the control or rifaximin treatment group (rifaximin 400 mg twice daily for 8 weeks). Primary outcome was the total liver-related score, consisting of changes in cirrhosis-related complications including rebleeding, ascites, HE and portal vein thrombosis (PVT). The 16S rDNA sequencing analysis was conducted with gastric lavage fluid samples for the analysis of gastric microbiota., Results: During the 8-week follow-up, the total liver-related score decreased significantly upon rifaximin therapy (-0.35 ± 0.14 vs 0.05 ± 0.14, p = 0.0465) as well as serum C-reactive protein (CRP) (p = 0.019) and interleukin-8 (p = 0.025) compared with the control group. The rate of PVT recanalization was significantly higher in the rifaximin group (p = 0.012). Prominent difference in gastric microbiota between the two groups was observed, and the rifaximin group had a higher abundance of several taxa which were dysregulated in the progression of cirrhosis. CRP was correlated with several taxa including Alphaproteobacteria, Rhizobiales and Collinsella., Conclusions: Rifaximin may improve cirrhosis-related complications, including PVT, in patients with previous GEVB through anti-inflammatory and microbiota-modulating functions., Trial Registration Number: NCT02991612., (© 2024 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Competing Interests: Dr. Szumita received funding from Trevena. Dr. Barletta received funding from Wolters Kluwer and Lexicomp. Dr. DePriest received funding from Baxter Channel One. Dr. Wischmeyer received funding from Abbott, Baxter, Fresenius Kabi Deutschland GmbH, Danone and Nutricia, Musclesound, Dutch State Mines, and Nestle. Dr. Argetsinger disclosed that she is an employee of the University of Michigan Health West and Bronson Methodist Hospital and Georgetown University School of Nursing. Dr. Dionne received funding from the Canadian Institutes of Health Research. Dr. Granholm received funding from Sygeforsikringen “Danmark.” The remaining authors have disclosed that they do not have any potential conflicts of interest.

Background: Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for preventing upper gastrointestinal bleeding in critically ill patients. However, concerns have arisen about the possible harms of using PPIs, including potentially increased risk of pneumonia, Clostridioides difficile infection, and more seriously, an increased risk of death in the most severely ill patients. Triggered by the REVISE trial, which is a forthcoming large randomized trial comparing pantoprazole to placebo in invasively mechanically ventilated patients, we will conduct this systematic review to evaluate the efficacy and safety of PPIs versus no prophylaxis for critically ill patients., Methods: We will systematically search randomized trials that compared gastrointestinal bleeding prophylaxis with PPIs versus placebo or no prophylaxis in adults in the intensive care unit (ICU). Pairs of reviewers will independently screen the literature, and for those eligible trials, extract data and assess risk of bias. We will perform meta-analyses using a random-effects model, and calculate relative risks for dichotomous outcomes and mean differences for continuous outcomes, and the associated 95% confidence intervals. We will conduct subgroup analysis to explore whether the impact of PPIs on mortality differs in more and less severely ill patients. We will assess certainty of evidence using the GRADE approach., Discussion: This systematic review will provide the most up-to-date evidence regarding the merits and limitations of stress ulcer prophylaxis with PPIs in critically ill patients in contemporary practice., (© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

Rationale: Critically ill adults can develop stress-related mucosal damage from gastrointestinal hypoperfusion and reperfusion injury, predisposing them to clinically important stress-related upper gastrointestinal bleeding (UGIB)., Objectives: The objective of this guideline was to develop evidence-based recommendations for the prevention of UGIB in adults in the ICU., Design: A multiprofessional panel of 18 international experts from dietetics, critical care medicine, nursing, and pharmacy, and two methodologists developed evidence-based recommendations in alignment with the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Conflict-of-interest policies were strictly followed during all phases of guideline development including task force selection and voting., Methods: The panel members identified and formulated 13 Population, Intervention, Comparison, and Outcome questions. We conducted a systematic review for each question to identify the best available evidence, statistically analyzed the evidence, and then assessed the certainty of the evidence using the GRADE approach. We used the evidence-to-decision framework to formulate the recommendations. Good practice statements were included to provide additional guidance., Results: The panel generated nine conditional recommendations and made four good practice statements. Factors that likely increase the risk for clinically important stress-related UGIB in critically ill adults include coagulopathy, shock, and chronic liver disease. There is no firm evidence for mechanical ventilation alone being a risk factor. Enteral nutrition probably reduces UGIB risk. All critically ill adults with factors that likely increase the risk for stress-related UGIB should receive either proton pump inhibitors or histamine-2 receptor antagonists, at low dosage regimens, to prevent UGIB. Prophylaxis should be discontinued when critical illness is no longer evident or the risk factor(s) is no longer present despite ongoing critical illness. Discontinuation of stress ulcer prophylaxis before transfer out of the ICU is necessary to prevent inappropriate prescribing., Conclusions: The guideline panel achieved consensus regarding the recommendations for the prevention of stress-related UGIB. These recommendations are intended for consideration along with the patient's existing clinical status., Competing Interests: Dr. Szumita received funding from Trevena. Dr. Barletta received funding from Wolters Kluwer and Lexicomp. Dr. DePriest received funding from Baxter Channel One. Dr. Wischmeyer received funding from Abbott, Baxter, Fresenius Kabi Deutschland GmbH, Danone and Nutricia, Musclesound, Dutch State Mines, and Nestle. Dr. Argetsinger disclosed that she is an employee of the University of Michigan Health West and Bronson Methodist Hospital and of Georgetown University School of Nursing. Dr. Dionne received funding from the Canadian Institutes of Health Research. Dr. Granholm received funding from Sygeforsikringen “Danmark.” The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Introduction: Aspirin and anti-P2Y12 are widely prescribed in cardiovascular patients, often in combination with proton pump inhibitors (PPIs) to limit the risk of upper gastrointestinal bleedings. The potential interaction between PPIs and antiplatelet agents has been widely discussed, but doubts remain as to whether PPIs may reduce the cardiovascular protection provided by aspirin, prasugrel, ticagrelor, and clopidogrel., Areas Covered: Many pharmacokinetic (PK) and pharmacodynamic (PD) studies have confirmed the interaction, especially between PPIs and clopidogrel, but with uncertain consequences on clinical outcomes. Therefore, we aimed to summarize the evidence for the widespread combined use of oral antiplatelet drugs and PPIs, to outline the current evidence supporting or opposing drug-drug interaction, and to discuss the clinical implications of such interactions., Expert Opinion: A large body of evidence describes the PK/PD interaction of antiplatelet drugs with PPIs and its potential role in increasing clinical cardiovascular adverse events, but no solid clinical data have confirmed these effects. In the light of the published studies, there seems to be no restriction on the choice of PPI with aspirin, prasugrel, and/or ticagrelor. The choice of a PPI with no (or minimal) interference with the hepatic cytochrome P450 2C19 is preferred in patients receiving clopidogrel.

Background and Aims: Patients with Child-Turcotte-Pugh class B and C cirrhosis with upper gastrointestinal bleeding (UGIB) have systemic as well as localized (in the mucosa of the esophagus and stomach) fibrinolysis. The aim of this study was to evaluate the efficacy and safety of tranexamic acid in the treatment of acute UGIB in patients with cirrhosis., Approach and Results: A total of 600 patients with advanced liver cirrhosis (Child-Turcotte-Pugh class B or C) presenting with UGIB were randomly allocated to either the tranexamic acid (n=300) or the placebo group (n=300). The primary outcome measure was the proportion of patients developing 5-day treatment failure. Failure to control bleeding by day 5 was seen in 19/300 (6.3%) patients in the tranexamic acid group and 40/300 (13.3%) patients in the placebo group ( p =0.006). Esophageal endoscopic variceal ligation (EVL) site as a source of failure to control bleeding by day 5 among patients undergoing first-time esophageal EVL (excluding patients with a previous post-EVL ulcer as a source of bleed) was seen in 11/222 (4.9%) patients in the tranexamic acid group and 27/225 (1212.0%) patients in the placebo group ( p =0.005). However, 5-day and 6-week mortality was similar in the tranexamic acid and placebo groups., Conclusions: Tranexamic acid significantly reduces the failure to control bleeding by day 5 and failure to prevent rebleeding after day 5 to 6 weeks in patients with advanced liver cirrhosis (Child-Turcotte-Pugh class B or C) presenting with UGIB, by preventing bleeding from the EVL site., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Balancing the safety and efficacy of antithrombotic agents in patients with gastrointestinal disorders is challenging because of the potential for interference with the absorption of antithrombotic drugs and for an increased risk of bleeding. In this Review, we address considerations for enteral antithrombotic therapy in patients with cardiovascular disease and gastrointestinal comorbidities. For those with gastrointestinal bleeding (GIB), we summarize a general scheme for risk stratification and clinical evidence on risk reduction approaches, such as limiting the use of concomitant medications that increase the risk of GIB and the potential utility of gastrointestinal protection strategies (such as proton pump inhibitors or histamine type 2 receptor antagonists). Furthermore, we summarize the best available evidence and potential gaps in our knowledge on tailoring antithrombotic therapy in patients with active or recent GIB and in those at high risk of GIB but without active or recent GIB. Finally, we review the recommendations provided by major medical societies, highlighting the crucial role of teamwork and multidisciplinary discussions to customize the antithrombotic regimen in patients with coexisting cardiovascular and gastrointestinal diseases., (© 2024. Springer Nature Limited.)

DA-9601 extracted from Artemisia asiatica contains a bioactive compound - eupatilin - that can protect against gastric mucosal damage through anti-inflammatory and anti-oxidative properties and is approved for treating acute and chronic gastritis in Korea, but their ability to protect gastrointestinal (GI) bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs) is unclear. We aimed to compare the protective effects of DA-9601 to those of proton pump inhibitors (PPI) and rebamipide against upper and lower GI bleeding in patients with rheumatoid arthritis (RA) undergoing long-term NSAIDs therapy using the Korean Health Insurance Review and Assessment database. In this nationwide retrospective cohort study, we evaluated patients with RA who concurrently received NSAIDs for >3 months with DA-9601, PPI, or rebamipide between January 2015 and December 2017. The index date was the date of NSAIDs initiation, and all patients were followed up until December 2020 to detect upper and lower GI bleeding. In total, 24,258 patients with RA were eligible, and 5468 (22.5%), 4417 (18.2%), and 14,373 (59.3%) received DA-9601, PPI, or rebamipide, respectively, on the index date. During follow-up, upper and lower GI bleeding occurred in 508 (2.1%) and 402 (1.6%) patients with RA, respectively. The incidence rate of upper and lower GI bleeding was 615/100,000 and 485/100,000 person-years, respectively. Among patients with RA receiving DA-9601, PPI, or rebamipide, the frequencies of NSAIDs-induced upper GI bleeding were 0.5%, 0.4%, and 1.2%, respectively. The frequencies of NSAIDs-induced lower GI bleeding were 0.4%, 0.4%, and 0.9%, respectively. The incidence of NSAIDs-induced upper GI bleeding in patients with RA receiving DA-9601, PPI, and rebamipide was 601/100,000, 705/100,000, and 596/100,000 person-years, respectively, while the incidence of NSAIDs-induced lower GI bleeding in the same groups was 449/100,000, 608/100,000, and 465/100,000 person-years, respectively. In the multivariate Cox regression analysis, no significant difference was observed in lower and upper GI bleeding hazards between patients with RA using DA-9601, PPI, and rebamipide. Our results suggest that DA-9601 may exhibit protection against NSAIDs-induced GI bleeding that is comparable to those of PPI and rebamipide in patients with RA., Competing Interests: All authors declare no conflicts of interest., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear., Methods: In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted secondary outcomes included ventilator-associated pneumonia, Clostridioides difficile infection, and patient-important bleeding., Results: A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other secondary outcomes were similar in the two groups., Conclusions: Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.)., (Copyright © 2024 Massachusetts Medical Society.)

Objective: A set of indicators has been reported to measure the quality of care for cirrhotic patients, and previously published studies report variable adherence rates to these indicators. This study aimed to assess the quality of care provided to cirrhotic outpatients before and after an educational intervention by determining its impact on adherence to quality indicators., Methods: We conducted a quasi-experimental, cross-sectional study including 324 cirrhotic patients seen in 2017 and 2019 at a tertiary teaching hospital in Spain. Quality indicators were assessed in five domains: documentation of cirrhosis etiology, disease severity assessment, hepatocellular carcinoma (HCC) screening, variceal bleeding prophylaxis, and vaccination. After identifying areas for improvement, an educational intervention was implemented. A second evaluation was performed after the intervention to assess changes in adherence rates., Results: Before the intervention, adherence rates were excellent (>90%) for indicators related to variceal bleeding prophylaxis and documentation of cirrhosis etiology, acceptable (60-80%) for HCC screening and disease severity assessment, and poor (<50%) for vaccinations. After the educational intervention, there was a statistically significant improvement in adherence rates for eight indicators related to HCC screening (70-90%), disease severity assessment (90%), variceal bleeding prophylaxis (>90%), and vaccinations (60-90%)., Conclusion: Our study demonstrates a significant improvement in the quality of care provided to cirrhotic outpatients after an educational intervention. The findings highlight the importance of targeted educational interventions to enhance adherence to quality indicators in the management of cirrhosis., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Competing Interests: Disclosure All authors disclosed no financial relationships.

Esophageal and gastric varices (EGV) bleeding is a dangerous side effect of liver cirrhosis. Ascites may affect the effectiveness of carvedilol in preventing EGV rebleeding. A retrospective analysis was done on patients with EGV bleeding who visited our gastroenterology department between January 1, 2015, and October 29, 2020, and were given carvedilol therapy again. Patients were classified based on whether they had ascites. The primary outcome was EGV rebleeding. A total of 286 patients were included, with a median follow-up of 24.0 (19.0-42.0) months, comprising those without ascites (N = 155) and those with ascites (N = 131). The mean age of the patients was 55.15 ± 12.44 years, and 177 (61.9%) of them were men. There were 162 (56.6%) Child-Pugh A grades. The etiology of cirrhosis included 135 (47.2%) cases of hepatitis B. After carvedilol therapy, the patient's portal vein diameter (DPV) was widened (p < 0.05), velocity of portal vein (VPV) was slowed (p = 0.001). During the 1-year follow-up, patients with ascites had a substantially higher rebleeding rate than patients without ascites, with 24 (18.3%) versus 13 (8.4%), respectively (p = 0.013). On univariate analysis, ascites was a risk factor for rebleeding (p = 0.015). The multivariate analysis remained significant after adjusting for age, gender, etiology of cirrhosis, and previous endoscopic treatment, with OR of 2.37 (95% CI: 1.12-5.04; p = 0.025). Ascites was a risk factor for EGV rebleeding in patients undergoing carvedilol therapy. After carvedilol therapy, the patient's DPV was widened and VPV was slowed., (© 2024 The Author(s). Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Background: The goal of this systematic review was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients., Methods: We included randomized trials comparing proton-pump inhibitors versus placebo or no prophylaxis in critically ill adults, performed meta-analyses, and assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. To explore the effect of proton-pump inhibitors on mortality based on disease severity, a subgroup analysis was conducted combining within-trial subgroup data from the two largest trials and assessed credibility using the Instrument for Assessing the Credibility of Effect Modification Analyses., Results: Twelve trials that enrolled 9533 patients were included. Proton-pump inhibitors were associated with a reduced incidence of clinically important upper gastrointestinal bleeding (relative risk [RR], 0.51 [95% confidence interval (CI), 0.34 to 0.76]; high certainty evidence). Proton-pump inhibitors may have little or no effect on mortality (RR, 0.99 [95% CI, 0.93 to 1.05]; low certainty). Within-trial subgroup analysis with intermediate credibility suggested that the effect of proton-pump inhibitors on mortality may differ based on disease severity. Subgroup results raise the possibility that proton-pump inhibitors may decrease 90-day mortality in less severely ill patients (RR, 0.89; 95% CI, 0.80 to 0.98) and may increase mortality in more severely ill patients (RR, 1.08; 95% CI, 0.96 to 1.20]. Proton-pump inhibitors may have no effect on pneumonia and little or no effect on Clostridioides difficile infection (low certainty)., Conclusions: High certainty evidence supports the association of proton-pump inhibitors with decreased upper gastrointestinal bleeding. Proton-pump inhibitors may have little or no effect on mortality, although a decrease in mortality in less severely ill patients and an increase in mortality in more severely ill patients remain possible. (PROSPERO number CRD42023461695.).

Background: Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers (RASi) on portal hypertension. Still, their effects on hard cirrhosis-related clinical endpoints, such as variceal bleeding and bleeding-related mortality, remain to be investigated., Methods: Thus, we recorded the use of statins, metformin and RASi in a large cohort of cirrhotic patients undergoing endoscopic band ligation (EBL) for primary (PP, n = 440) and secondary bleeding prophylaxis (SP, n = 480) between 01/2000 and 05/2020. Variceal (re-) bleeding and survival rates were compared between patients with vs. without these co-medications., Results: A total of 920 cirrhotic patients with varices were included. At first EBL, median MELD was 13 and 515 (56%) patients showed ascites. Statins, metformin and RASi were used by 49 (5.3%), 74 (8%), and 91 (9.9%) patients, respectively. MELD and platelet counts were similar in patients with and without the co-medications of interest. Rates of first variceal bleeding and variceal rebleeding at 2 years were 5.2% and 11.7%, respectively. Neither of the co-medications were associated with decreased first bleeding rates (log-rank tests in PP: statins p = 0.813, metformin p = 0.862, RASi p = 0.919) nor rebleeding rates (log-rank tests in SP: statin p = 0.113, metformin p = 0.348, RASi p = 0.273). Similar mortality rates were documented in patients with and without co-medications for PP (log-rank tests: statins p = 0.630, metformin p = 0.591, RASi p = 0.064) and for SP (statins p = 0.720, metformin p = 0.584, RASi p = 0.118)., Conclusion: In clinical practice, variceal bleeding and mortality rates of cirrhotic patients were not reduced by co-medication with statins, metformin or RASi. Nevertheless, we recommend the use of these co-medications by indication, as they may still exert beneficial effects on non-bleeding complications in patients with liver cirrhosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Pfisterer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Rebamipide has been widely co-prescribed with non-steroidal anti-inflammatory drugs (NSAIDs) in Japan for decades. This study aimed to evaluate the effectiveness of rebamipide in preventing upper gastrointestinal bleeding in new users of NSAIDs without risk factors of NSAID-induced ulcers other than age., Methods: A nested case-control study was conducted using medical claims data of 1.66 million inhabitants of 17 municipalities participating in Japan's Longevity Improvement & Fair Evidence study. The cohort entry (t0) corresponded to a new user of NSAIDs for osteoarthritis or low back pain. Patients with risk factors of NSAID-induced ulcers other than age were excluded. Cases were defined as patients who underwent gastroscopy for upper gastrointestinal bleeding (occurrence date was defined as index date). A maximum of 10 controls were selected from non-cases at the index date of each case by matching sex, age, follow-up time, and type and dosage of NSAIDs. Exposure to rebamipide was defined as prescription status from t0 to index date: Non-user (rebamipide was not co-prescribed during the follow-up period), Continuous-user (rebamipide was co-prescribed from t0 with the same number of tablets as NSAIDs), and Irregular-user (neither Non-user nor Continuous-user). Conditional logistic regression analysis was conducted to estimate each category's odds ratio compared to non-users., Findings: Of 67,561 individuals who met the inclusion criteria, 215 cases and 1,516 controls were selected. Compared with that of Non-users, the odds ratios and 95% confidence interval were 0.65 (0.44-0.96) for Continuous-users and 2.57 (1.73-3.81) for Irregular-users., Conclusions: Continuous co-prescription of rebamipide significantly reduced the risk of upper gastrointestinal bleeding in an Asian cohort of new users of NSAIDs with osteoarthritis or low back pain without risk factors other than age., Competing Interests: Authors with competing interests I have read the journal’s policy and the authors of this manuscript have the following competing interests:Yasuharu Nakashima received research grants from Chugai Pharmaceutical Co., Ltd., AYUMI Pharmaceutical Corporation, EA Pharma Co., Ltd., KYOCERA Corporation, and Zimmer Biomet G.K. All other authors have no conflicts of interest to disclose. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Yamate et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Competing interests: AC is a consultant for ERBE. RM is a consultant for ERBE, Fujifilm, 3DMatrix and Boston Scientific. CH is a consultant for Alpha-Sigma, Fujifilm, Medtronic, Norgine, Olympus and Pentax. AR is a consultant for Medtronic, ERBE, Fujifilm and Olympus. Others authors have nothing to declare.

Background National guidelines no longer recommend adults 60 years of age and older to begin treatment with low-dose daily aspirin for primary prevention of atherosclerotic cardiovascular disease (CVD) due to a lack of proven net benefit and a higher risk of bleeding. Objective The objective of this cross-sectional retrospective analysis was to evaluate the appropriateness of low-dose aspirin prescribing and subsequent gastrointestinal bleeding in older persons receiving primary care in a large academic health system. Setting Large, academic health system within Colorado. Patients Patients with an active order for daily low-dose aspirin as of July 1, 2021, were assessed for appropriateness based on indication (primary vs secondary prevention) and use of a concomitant proton-pump inhibitor (PPI). Incident gastrointestinal bleeds (GIBs) in the subsequent 12 months and GIB risk factors were also evaluated. Results A total of 19,525 patients were included in the analysis. Eighty-nine percent of patients identified as White and 54% identified as male. Of the total cohort, 44% had CVD and 19% were co-prescribed a PPI. GIB occurred in 247 patients (1.27%) within the subsequent year. Risk factors significantly associated with a GIB within 1 year included: history of GIB, history of peptic ulcer disease, other esophageal issue (esophagitis, Barrett's esophagus, Mallory Weiss tears, etc.), 75 years of age or older, and history of gastroesophageal reflux disease. Conclusion This evaluation found that many older persons at this institution may be inappropriately prescribed aspirin, providing opportunities for pharmacists to improve medication safety by deprescribing aspirin among primary prevention patients or potentially co-prescribing a PPI in secondary prevention patients.

Background: Antisecretory drugs are commonly prescribed with clopidogrel-based dual antiplatelet therapy (DAPT) to prevent gastrointestinal bleeding in high-risk patients after percutaneous coronary intervention (PCI). However, omeprazole and esomeprazole (inhibiting proton pump inhibitors [PPIs]) may increase cardiovascular event rates on co-administration with clopidogrel. This study aimed to examine trends in the use of antisecretory agents in patients administered clopidogrel-based DAPT and the concomitant use of clopidogrel and inhibiting PPIs., Methods: We used National Inpatient Sample data compiled by the Health Insurance Review & Assessment Service from 2009 to 2020. Further, we identified patients who were prescribed clopidogrel-based DAPT after PCI and investigated the concomitant use of antisecretory agents with clopidogrel. To verify the annual trend of drug utilization, we used the Cochran-Armitage trend test., Results: From 2009 to 2020, the percentage of H2 receptor antagonist users decreased steadily (from 82.5% in 2009 to 25.3% in 2020); instead, the percentage of PPI users increased (from 23.7% in 2009 to 82.0% in 2020). The use of inhibiting PPI also increased (from 4.2% in 2009 to 30.7% in 2020). Potassium competitive acid blockers (P-CABs) were rarely used before 2019; however, in 2020, it accounted for 7.8% of the antisecretory users., Conclusions: Our study demonstrates that the use of inhibiting PPIs increased steadily in patients administered clopidogrel-based DAPT therapy. This is a major concern since the concomitant use of inhibiting PPIs with clopidogrel could increase the risk of cardiovascular events., (© 2024 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Objectives: Endoscopic ultrasound (EUS)-guided injection of cyanoacrylate (CYA) for primary prophylaxis (PP) of gastric varices (GV) is controversial. This study evaluates the safety and efficacy of this intervention., Methods: Patients treated for PP of GV bleeding by EUS injection of CYA with or without coils were identified. Endoscopic techniques, outcomes, and adverse events (AEs) were reviewed and compared with a group treated for secondary prophylaxis (SP). Patients were followed until: (i) loss to follow-up; (ii) GV bleeding; (iii) interventional radiology or surgery decompression; (iv) liver transplant; or (v) death or comfort care., Results: One hundred and nineteen patients (61 men; mean 59 ± 12 years) underwent EUS for PP (n = 24) or SP (n = 95). The PP group was treated with CYA alone (n = 18) or with coils (n = 4). Eight (33%) mild (n = 6) or moderate (n = 2) AEs and no index GV bleeding occurred during a mean of 6.1 ± 5.9 months follow-up. Repeat EUS in 22 (92%) PP patients showed 7 (32%) residual GVs, which were retreated with CYA alone (n = 6) or with coils (n = 1). Two (29%) mild (n = 1) or moderate (n = 1) AEs occurred after repeat EUS and 1/22 (5%) index GV bleed occurred during a mean 23 ± 25 months follow-up. Compared to the SP group, the PP group had lower Model for End-stage Liver Disease (MELD) score (P = 0.03), fewer GV stigmata (P < 0.001), required less CYA (P = 0.019) during index EUS, and had a longer time between index and surveillance EUS (P = 0.014). The incidence of AEs and GV bleeding between the two groups were similar., Conclusion: Posttreatment GV bleeding and AEs are similar following EUS-guided primary and secondary GV prophylaxis., (© 2023 Japan Gastroenterological Endoscopy Society.)

Background: Overt hepatic encephalopathy remains a serious complication after TIPS. Concomitant SPSS is associated with an increased risk of HE in patients treated with TIPS., Purpose: To perform a systematic review and meta-analysis on the effectiveness and safety of the prophylactic embolization of SPSS at the time of TIPS creation., Materials and Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched up to April 2023 to identify studies on the association between antegrade embolized SPSS before TIPS placement and the incidence of post-TIPS HE. Odds ratios (ORs) and their corresponding 95% CIs were used to identify significant differences in the outcomes., Results: Four studies enrolling 1243 patients with cirrhosis who received TIPS for variceal bleeding were included. A meta-analysis revealed that TIPS without simultaneous SPSS embolization was associated with an increased risk of overt HE (OR 2.41, 95% CI 1.32-4.38; p = 0.004). The risks of mortality (0.79, 95% CI 0.58-1.07; p = 0.13), variceal rebleeding (0.94, 95% CI 0.66-1.34; p = 0.74) and shunt dysfunction (1.40, 95% CI 0.51-3.83; p = 0.51) did not significantly differ among the groups., Conclusion: SPSS prevalence was associated with an increased risk of overt HE after TIPS. Concurrent antegrade SPSS embolization during TIPS creation reduced the risk for overt HE without increasing other complications., Competing Interests: Conflict of interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Transjugular intrahepatic portosystemic shunt (TIPS) is a medical procedure that has been used to manage variceal bleeding and ascites in patients with cirrhosis. It can prevent further decompensation and improve the survival of high-risk decompensated patients. Recent research indicates that TIPS could increase the possibility of recompensation of decompensated cirrhosis when it is combined with adequate suppression of the causative factor of liver disease. However, the results of the studies have been based on retrospective analysis, and further validation is required by conducting randomized controlled studies. In this context, we highlight the limitations of the current studies and emphasize the issues that must be addressed before TIPS can be recommended as a potential recompensating tool., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Although proton pump inhibitors (PPIs) or potassium-competitive acid blocker (PCAB) are useful in peptic ulcer prevention, their efficacy in preventing other gastrointestinal bleeding remains unclear. This study aimed to identify the status of gastrointestinal bleeding in the modern era when PPIs are widely used., Methods: This study included patients who underwent percutaneous coronary intervention (PCI) between 2018 and 2019 at two high-volume centers. Patients were categorized based on whether they experienced gastrointestinal bleeding within 2 years of PCI into groups A (patients who experienced gastrointestinal bleeding within 2 years after PCI) and B (patients who did not experience gastrointestinal bleeding)., Results: Groups A and B included 21 (4.1%) and 494 (95.9%) patients, respectively (a total of 515 patients). Age at the initial PCI (77.8±2.4 and 72.0±0.5 years in groups A and B, respectively; p = 0.02), weight (53.8±3.2 and 61.8±0.7 kg in groups A and B, respectively; p = 0.01), and concomitant warfarin use (14.3% and 2.0% in groups A and B, respectively; p = 0.0005) were significantly different between the groups. The high bleeding risk rate (90.5% and 47.6% in groups A and B, respectively; p = 0.0001) was significantly different between the groups. A total of 95.9% of patients were taking PPIs or PCAB without significant differences between the groups. However, only one patient, who was taking steroids, had a gastric ulcer during PCAB treatment., Conclusions: Acid-related upper gastrointestinal bleeding is largely controlled by PPIs in post-PCI patients. Furthermore, the risk factors for non-acid-related bleeding include older age, lower weight, and concomitant warfarin use., (© 2024. The Author(s).)

Antibiotic prophylaxis in patients with cirrhosis and acute variceal bleeding is part of the standard of care according to most clinical guidelines. However, with recent evidence arguing against antibiotic prophylaxis, the role of this intervention has become less clear., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: During the COVID-19 pandemic, many intensive care units (ICUs) halted research to focus on COVID-19-specific studies., Objective: To describe the conduct of an international randomized trial of stress ulcer prophylaxis (Re-Evaluating the Inhibition of Stress Erosions in the ICU [REVISE]) during the pandemic, addressing enrolment patterns, center engagement, informed consent processes, data collection, a COVID-specific substudy, patient transfers, and data monitoring., Methods: REVISE is a randomized trial among mechanically ventilated patients, comparing pantoprazole 40 mg IV to placebo on the primary efficacy outcome of clinically important upper gastrointestinal bleeding and the primary safety outcome of 90-day mortality. We documented protocol implementation status from March 11th 2020-August 30th 2022., Results: The Steering Committee did not change the scientific protocol. From the first enrolment on July 9th 2019 to March 10th 2020 (8 months preceding the pandemic), 267 patients were enrolled in 18 centers. From March 11th 2020-August 30th 2022 (30 months thereafter), 41 new centers joined; 59 were participating by August 30th 2022 which enrolled 2961 patients. During a total of 1235 enrolment-months in the pandemic phase, enrolment paused for 106 (8.6%) months in aggregate (median 3 months, interquartile range 2;6). Protocol implementation involved a shift from the a priori consent model pre-pandemic (188, 58.8%) to the consent to continue model (1615, 54.1%, p < 0.01). In one new center, an opt-out model was approved. The informed consent rate increased slightly (80.7% to 85.0%, p = 0.05). Telephone consent encounters increased (16.6% to 68.2%, p < 0.001). Surge capacity necessitated intra-institutional transfers; receiving centers continued protocol implementation whenever possible. We developed a nested COVID-19 substudy. The Methods Centers continued central statistical monitoring of trial metrics. Site monitoring was initially remote, then in-person when restrictions lifted., Conclusion: Protocol implementation adaptations during the pandemic included a shift in the consent model, a sustained high consent rate, and launch of a COVID-19 substudy. Recruitment increased as new centers joined, patient transfers were optimized, and monitoring methods were adapted., (© 2024. Crown.)

Gastrointestinal (GI) bleeding is one of the most common complications associated with the use of direct oral anticoagulants (DOAC). Clear algorithms exist for the emergency measures in (suspected) GI bleeding, including assessing the medication history regarding anti-platelet drugs and anticoagulants as well as simple coagulation tests during pre-endoscopic management. Platelet transfusions, fresh frozen plasma (FFP), or prothrombin complex concentrate (4F-PCC) are commonly used for optimizing the coagulation status. For severe bleeding under the thrombin inhibitor dabigatran, idarucizumab is available, and for bleeding under the factor Xa inhibitors rivaroxaban or apixaban, andexanet alfa is available as specific antidotes for DOAC antagonization. These antidotes represent emergency drugs that are typically used only after performing guideline-compliant multimodal measures including emergency endoscopy. Antagonization of oral anticoagulants should be considered for severe gastrointestinal bleeding in the following situations: (1) refractory hemorrhagic shock, (2) endoscopically unstoppable bleeding, or (3) nonavoidable delays until emergency endoscopy for life-threatening bleeding. After successful (endoscopic) hemostasis, anticoagulation (DOACs, vitamin K antagonist, heparin) should be resumed timely (i.e. usually within a week), taking into account individual bleeding and thromboembolic risk., Competing Interests: Dieses Manuskript fasst die wesentlichen Diskussionspunkte eines interdisziplinären Expertentreffens im Juli 2022 mit Vertreter*innen aus der Gastroenterologie, Intensivmedizin und Hämostaseologie zusammen, in dem die Bedeutung und mögliche Einsatzgebiete von spezifischen Antidots zur Antagonisierung der neuen/direkten orale Antikoagulantien (DOAK) bei schweren und lebensbedrohlichen gastrointestinalen (GI)-Blutungen diskutiert und herausgearbeitet wurde. Dieses Expertentreffen wurde durch die Fa. AstraZeneca (damals Alexion) finanziell unterstützt., (Thieme. All rights reserved.)

Background & Aims: In patients with atrial fibrillation (AF) receiving direct oral anticoagulant (DOAC), upper gastrointestinal bleeding (UGIB) is a serious complication. There are limited data on the benefit of preventive proton pump inhibitor (PPI) use to reduce the risk of UGIB in DOAC users., Methods: We included patients with AF receiving DOAC from 2015 to 2020 based on the Korean Health Insurance Review and Assessment database. The propensity score (PS) weighting method was used to compare patients with PPI use and those without PPI use. The primary outcome was hospitalization for UGIB. Weighted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) were evaluated using the Cox proportional hazards regression model., Results: A total of 165,624 patients were included (mean age: 72.2 ± 10.8 years; mean CHA 2 DS 2 -VASc score: 4.3 ± 1.8; mean HAS-BLED score: 3.3 ± 1.2). Among them, 99,868 and 65,756 were in the non-PPI group and PPI group, respectively. During a median follow-up of 1.5 years, the PPI group was associated with lower risks of hospitalization for UGIB and UGIB requiring red blood cell transfusion than non-PPI group (weighted HR, 0.825; 95% CI, 0.761-0.894 and 0.798; 95% CI, 0.717-0.887, respectively, both P < .001). The benefits of PPI on the risk of hospitalization for UGIB were greater in those with older age (≥75 years), higher HAS-BLED score (≥3), prior GIB history, and concomitant use of antiplatelet agent (all P-for-interaction < .1). Low-dose PPI was consistently associated with a lower risk of significant UGIB by 43.6-49.3% (P < .001)., Conclusions: In this large Asian cohort of patients with AF on DOAC, PPI co-therapy is beneficial for reducing the risk of hospitalization for UGIB, particularly in high-risk patients., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD)., Methods/design: The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25 mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is the time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child-Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival., Discussion: The BOPPP trial aims to investigate the clinical and cost-effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care., Ethics and Dissemination: The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation., Trial Registration: EUDRACT reference number: 2018-002509-78. ISRCTN reference number: ISRCTN10324656. Registered on April 24 2019., (© 2024. The Author(s).)

Managing gastrointestinal bleeding in patients using antithrombotic agents remains challenging in clinical practice. This review article provides a comprehensive and evidence-based approach to managing acute antithrombotic-related gastrointestinal bleeding, focusing on the triage of patients, appropriate resuscitation, and timely endoscopy. The latest clinical practice guidelines are highlighted to guide decisions concerning the use of reversal agents, temporary interruption, and resumption of antithrombotic drugs. Additionally, preventive measures are discussed to lower the risk of future bleeding and minimize complications among patients prescribed antithrombotic drugs., Competing Interests: Disclosure The authors report no conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Cirrhosis is associated with a high morbidity and mortality. One of the most serious and unpredictable complication of cirrhosis, with a high mortality rate, is bleeding from esophagogastric varices. Endoscopic screening of varices followed by primary prophylactic treatment with beta blockers or band ligation in the presence of large esophageal varices will reduce the variceal bleeding rates and thereby reduce mortality risks in those with advanced cirrhosis. There is a paucity of data on primary prophylaxis of gastric varices but secondary prophylaxis includes glue injection, balloon-occluded retrograde transvenous obliteration, or transjugular intrahepatic portosystemic shunting with coil embolization., Competing Interests: Disclosures The authors have no financial conflicts of interests and did not receive funding from any sources for this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Aim: Preventing rebleeding is crucial, but the best prevention technique for patients with cirrhosis and portal vein thrombosis (PVT) remains debatable. Therefore, this systematic review and meta-analysis compared a transjugular intrahepatic portosystemic shunt (TIPS) with endoscopic therapy (ET) plus nonselective beta-blockers (NSBBs) for preventing variceal rebleeding in this patient population., Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched from their inception until May 18, 2023. The studies were screened using predetermined criteria, relevant data were extracted, and pooled analyses were performed using the Reviewer Manager 5.4.1 software., Results: We retrieved 1032 studies, of which 5 studies comprising a total of 272 patients were included. The postoperative variceal rebleeding rate was significantly lower in the TIPS group than in the ET + NSBBs group (odds ratio [OR] = 0.19, 95% confidence interval [CI] = 0.11-0.35, P < 0.05, I 2  = 0%), but the portal vein recanalization rate was higher (OR = 7.92, 95% CI = 3.04-20.67, P < 0.05, I 2  = 0%). The rates of hepatic encephalopathy (HE) and mortality did not differ between the groups., Conclusions: Our results suggest that TIPS prevents variceal rebleeding without increasing the hepatic encephalopathy risk more effectively than ET plus NSBBs, but this benefit did not translate into improved survival. Thus, it may be preferable to ET plus NSBBs for preventing variceal rebleeding in patients with cirrhosis and PVT. However, more large-scale and multicenter randomized controlled trials involving other patient populations are required to verify the clinical efficacy of both these treatments and ensure generalizability., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Objective: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC)., Design: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression., Results: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL., Conclusion: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D., Trial Registration Number: NCT01970748., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

A significant problem encountered in the resection of large, complex colonic polyps is delayed bleeding. This can occur up to two weeks after the procedure and is a significant source of comorbidity. Untreated it can prove life threatening. It is therefore a priority of modern endoscopy to develop and employ techniques to minimaize this. In this article we will review and discuss the evidence base and controversies in this field, with cold EMR technique, Post-EMR clip closure, and topical haemostatic agents., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Background/aims: Mucoprotective agents, such as eupatilin, are often prescribed to prevent gastrointestinal (GI) bleeding in addition to an acid suppressant despite the absence of a large-scale study. We evaluated the additional effect of eupatilin on the prevention of GI bleeding in both the upper and lower GI tract in concomitant aspirin and acid suppressant users using the nationwide database of national claims data from the Korean National Health Insurance Service (NHIS)., Methods: An aspirin cohort was constructed using the NHIS claims data from 2013 to 2020. Patients who manifested with hematemesis, melena, or hematochezia were considered to have GI bleeding. A Cox proportional hazards regression model was used to determine the risk factors for GI bleeding associated with the concomitant use of GI drugs and other covariates among aspirin users., Results: Overall, a total of 432,208 aspirin users were included. The concurrent use of an acid suppressant and eupatilin (hazard ratio [HR] = 0.85, p = 0.016, vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding. Moreover, a more than 3-month duration (HR = 0.88, p = 0.030) of acid suppressant and eupatilin prescription (vs. acid suppressant only) was a statistically significant preventive factor for GI bleeding., Conclusion: Eupatilin administration for ≥ 3 months showed additional preventive effect on GI bleeding in concomitant aspirin and acid suppressant users. Thus, cotreatment with eupatilin with a duration of 3 months or longer is recommended for reducing GI bleeding among aspirin plus acid suppressant users.

Background: Low-dose aspirin (LDA) administration is associated with an elevated risk of recurring peptic ulcer (PU) and gastrointestinal (GI) hemorrhage., Aims: This systematic review and Bayesian network meta-analysis aimed to comprehensively assess the effectiveness of diverse medications in preventing the recurrence of PU and GI hemorrhage in patients with a history of PU receiving long-term LDA therapy., Methods: This systematic review and network meta-analysis followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered on PROSPERO (CRD42023406550). We searched relevant studies in main databases from inception to March 2023. All statistical analyses were performed using R (version 4.1.3), with the "Gemtc" (version 1.0-1) package. The pooled risk ratio (RR), corresponding 95% credible interval (95% CrI), and the surface under the cumulative ranking curve (SUCRA) were calculated., Results: 11 Randomized clinical trials (RCTs) were included. The analysis underscored pantoprazole was the most efficacious for reducing the risk of PU recurrence (RR [95% CrI] = 0.02 [0, 0.28]; SUCRA: 90.76%), followed by vonoprazan (RR [95% CrI] = 0.03 [0, 0.19]; SUCRA: 86.47%), comparing with the placebo group. Pantoprazole also performed well in preventing GI hemorrhage (RR [95% CrI] = 0.01[0, 0.42]; SUCRA: 87.12%) compared with Teprenone., Conclusions: For patients with a history of PU receiving LDA, pantoprazole and vonoprazan might be the optimal choices to prevent PU recurrence and GI hemorrhage., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: A previous individual patient data meta-analysis (IPD-MA) showed that compared with drugs+endoscopy, the placement of transjugular portosystemic shunt within 72 hours of admission (pre-emptive transjugular intrahepatic portosystemic shunt: p-TIPS) increases the survival of high-risk patients (Child-Pugh B+ active bleeding and Child-Pugh C<14 points) with cirrhosis and acute variceal bleeding. However, the previous IPD-MA was not a two-stage meta-analysis, did not consider the potential risk of selection bias of observational studies, and did not include the most recent randomized clinical trial. We performed an updated and revised IPD-MA to reassess the efficacy of p-TIPS, addressing all previous issues., Approach and Results: We included all studies from the previous IPD-MA and searched for other possible eligible publications until September 2022. We performed a two-stage IPD-MA of data from 8 studies (4 randomized clinical trials and 4 observational). In addition, we performed a sensitivity analysis excluding those patients dying up to the first 72 hours after admission in the Drugs+Endoscopy arms of the 4 observational studies. The primary end point was the effects of p-TIPS versus Drugs+Endoscopy on 1-year survival.We identified 1389 patients (342 p-TIPS and 1047 Drugs+Endoscopy). The two-stage IPD-MA showed that p-TIPS significantly reduced the mortality in the overall population (HR=0·43, 95% CI: 0.32-0.60, p <0.001. This effect was observed in both subgroups of patients with Child-Pugh. The sensitivity analysis confirmed the survival benefit of p-TIPS., Conclusions: The updated two-stage IPD-MA confirms the significant survival advantage of p-TIPS in high-risk patients with cirrhosis and acute variceal bleeding. As a result, we recommend p-TIPS as the preferred first-choice treatment for these patients., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Over the past decade, significant advancements in pharmacological, endoscopic, and radiographic treatments have emerged in the management of patients with cirrhosis and esophagogastric varices or variceal hemorrhage. These advances have been in several areas, including the role of screening and primary prophylaxis (preventing an initial variceal bleed), evaluation and management of acute esophagogastric variceal hemorrhage, and in preventing variceal rebleeding. Therefore, we believe there is a need for an updated, evidence-based "narrative review" on this important clinical topic that will be relevant for internists, hospitalists, intensive care unit physicians, and those in training. We believe the guidance presented in this narrative review will enhance daily medical practice of health care professionals and has the potential to improve quality of care for these complex patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)