Treatment Of Thromboembolic Events Research Articles

Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings.

The use of non-vitamin K antagonist oral anticoagulants (NOACs) has brought a significant progress in the management of cardiovascular diseases, considered clinically superior to vitamin K antagonists (VKAs) particularly in the prevention and treatment of thromboembolic events. In addition, numerous advantages such as fixed dosing, lack of laboratory monitoring, and fewer food and drug-to-drug interactions make the use of NOACs superior to VKAs. While NOACs are synthetic drugs prescribed for specific conditions, nattokinase (NK) is a natural enzyme derived from food that has potential health benefits. Various experimental and clinical studies reported the positive effects of NK on the circulatory system, including the thinning of blood and the dissolution of blood clots. This enzyme showed not only fibrinolytic activity due to its ability to degrade fibrin, but also an affinity as a substrate for plasmin. Recent studies have shown that NK has additional cardioprotective effects, such as antihypertensive and anti-atherosclerotic effects. In this narrative review, we presented the cardioprotective properties of two different approaches that go beyond anticoagulation: NOACs and NK. By combining evidence from basic research with clinical findings, we aim to elucidate the comparative cardioprotective efficacy of these interventions and highlight their respective roles in modern cardiovascular care.

Overdosing of direct oral anticoagulants

Direct oral anticoagulants (DOAC) are increasingly used for prophylaxis and treatment of thromboembolic events. Incorrectly dosed DOAC treatment is associated with excess mortality. This article aims at raising awareness of DOAC overdosing and its causes as well as presenting adiagnostic and therapeutic work-up. Based on acase presentation, astructured review of the current literature on DOAC overdosing was performed and treatment recommendations were extracted. In addition to wittingly or unwittingly increased DOAC intake, common causes of overdose are inadequate dose adjustment for concomitant medication or comorbidities. Global coagulation testing should be supplemented with DOAC-specific testing. Severe bleeding and the need for invasive diagnostics or urgent surgery represent indications for treating DOAC overdoses. Based on the cause of an DOAC overdose, active charcoal, endoscopic pill rescue, antagonization with idarucizumab or andexanet alfa and the targeted substitution of coagulation factors represent treatment options. The sensitization of clinicians is important to ensure atimely diagnosis and adequate treatment of DOAC overdosing. This report provides an overview of current knowledge on diagnostics and treatment; however, further studies are necessary to improve the existing algorithms.

Efficacy and safety of antithrombotic therapy for preventing and treating pediatric thromboembolic disease: a systematic review

This review used traditional and network meta-analyses (NMA) to conduct a comprehensive study of antithrombotic therapies in children with thromboembolic disease. We searched the PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases from their inception to 26 February, 2023. And we finally included 16 randomized controlled trials. In the prevention of thromboembolic events (TEs), the use of anticoagulants had a low risk of TEs (relative risk (RR) 0.73, 95% CI 0.56 to 0.94) and a high risk of minor bleeding (RR 1.43, 95% CI 1.09 to 1.86) compared with no anticoagulants. In the treatment of TEs, direct oral anticoagulants (DOACs) were not inferior to standard anticoagulation in terms of efficacy and safety outcomes. In NMA, rivaroxaban and apixaban showed the lowest risk for TEs and major or clinically relevant nonmajor bleeding. According to the overall assessment of efficacy and safety, dabigatran may be the best choice for children with thromboembolic disease. The results of our study will provide references and suggestions for clinical drug selection.

Apixaban and clopidogrel in a fixed-dose combination: Formulation and in vitro evaluation

Fixed-dose combination (FDC) products represent a novel, safe, and cost-effective formulation. Combined use of anticoagulant and antiplatelet medications is common among comorbid cardiovascular patients. This study aimed to formulate FDC tablets for Apixaban and Clopidogrel, as prophylaxis and treatment of thrombo-embolic events. FDC tablets were developed by combining small tablets of Immediate-Release Clopidogrel 75 mg and Extend-Release Apixaban 5 mg through direct compression and wet granulation. Particularly, Apixaban tablets were developed using design expert software, and various types and concentrations of polymers were entered. For Clopidogrel tablets, various diluents were used to develop the formulation. Then, the dissolution profile for each formula was studied. Finally, the optimized formulations were encapsulated within hard gelatin capsules. Apixaban formulation followed zero-order with super case Ⅱ transport mechanism as the dominant mechanism of drug release. The Apixaban drug release rate was affected by the type and concentration of the polymers in the formulation (P < 0.05). As the HPMC concentration was increased, Apixaban release was retarded. For, Clopidogrel, the formulated tablets with spray-dried lactose filler and sodium stearyl fumarate lubricant were found to be stable with good properties. In conclusion, the optimum formulation yielded Clopidogrel and extended-release Apixaban for 24 h with the desired in vitro drug dissolution.

Direct Oral Anticoagulants: An Overview of Indications, Pharmacokinetics, Comorbidities, and Perioperative Management.

Direct oral anticoagulants (DOACs) have catalyzed a significant paradigm shift in the landscape of anticoagulant therapy, emerging as pivotal agents for the prevention of stroke in atrial fibrillation and venous thromboembolism. Although the absolute advantages of DOACs over vitamin K antagonists (VKAs) may appear modest, clinical guidelines advocate for their preference across various indications, attributing this endorsement to their ease of administration and heightened safety. DOACs find application in preventing and treating diverse cardiovascular conditions. With the progressive expansion of DOAC utility, clinicians encounter intricate decisions concerning the selection of appropriate agents, determination of optimal treatment duration, and utilization within specialized patient subgroups. Extensive evidence has substantiated the noninferiority or superiority of DOACs compared with VKAs in both prophylaxis and treatment of thromboembolic events. Notably, routine monitoring to evaluate treatment efficacy is not mandated for DOACs; however, they exhibit interactions with co-administered drugs and exert influence on functional coagulation assessments. This review aims to synthesize existing literature, encompassing the delineation of appropriate clinical indications, tailored employment in patients with specific concurrent conditions, needs in monitoring parameters, seamless transitions during shifts between anticoagulant regimens, and a glimpse into forthcoming perspectives in this evolving field.

A Comparison of Efficacy of Two Brands of Enoxaparin in COVID-19 Patients: A Pilot Study

Introduction: Enoxaparin is a complex and biologically derived low-molecular-weight Heparin which is approved for a variety of clinical indications associated with thromboembolic events such as Deep Vein Thrombosis and Venous Thromboembolism. During COVID-19 it was frequently used as prophylaxis in the treatment of thromboembolic events. Nowadays, many brands have come up in the market for the same.&#x0D; Objective: In Tricolour Hospital located in Vadodara, Gujarat, the ongoing brand of Enoxaparin 0.6 i.e., Clexane (Sanofi) falls short as well as in the pharmaceutical market. Hence, the management decided to procure another brand of Enoxaparin until Clexane is available to the vendors. Therefore, the present study was planned to study efficacy of two brands of Enoxaparin –one is Coguparine, (Venus Pharmaceuticals) and another LMWX- (Abbott) in COVID-19 patients in an isolation ward of hospital. The aim of present study was to compare the efficacy of two brands of Enoxaparin (Coguparine vs LMWX) for prophylactic treatment of thromboembolism observed in COVID-19 patients.&#x0D; Methodology: Patients were randomly divided into 2 groups- A and B. Patients in group A received Coguparine while patients in group B received LMWX. Statistical analysis was carried out using paired t-test.&#x0D; Results: The laboratory reports of patients in Group-A presented few abnormal improvements in the Complete blood count but there was no concrete evidence about the same. On the other hand, patients in Group-B receiving LMWX showed improvement in CBC profile. Also, there was significant difference observed in C-Reactive Protein and D-Dimer profiles in both the brands.&#x0D; Conclusion: This showed that for the cost-effective treatment and procurement of Enoxaparin there is no harm in using generic formulation of Enoxaparin as and when required. But LMWX was proved to be of standard quality in terms of efficacy.

Pharmacokinetics and pharmacodynamics of Abelacimab (MAA868), a novel dual inhibitor of Factor XI and Factor XIa

BackgroundFactor XI (FXI) inhibition offers the promise of hemostasis‐sparing anticoagulation for the prevention and treatment of thromboembolic events. Abelacimab (MAA868) is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activated FXI. ObjectivesTo investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single dose intravenous and multiple dose subcutaneous administration of abelacimab in healthy volunteers and patients with atrial fibrillation, respectively. Patients/MethodsIn study ANT‐003, healthy volunteers were administered single intravenous doses of abelacimab (30–150 mg) or placebo. The ANT‐003 study also included a cohort of obese but otherwise healthy subjects. In study ANT‐004, patients with atrial fibrillation were administered monthly subcutaneous doses of abelacimab (120 mg and 180 mg), or placebo, for 3 months. Key PK and PD parameters, including activated partial thromboplastin time (aPTT) and free FXI levels, as well as anti‐drug antibodies (ADA) were assessed. ResultsFollowing intravenous administration of abelacimab, the terminal elimination half‐life ranged from 25 to 30 days. One hour after the start of the intravenous infusion greater than 99% reductions in free FXI levels were observed. Following once monthly subcutaneous administration, marked reductions from baseline in free FXI levels were sustained. Parenteral administration of abelacimab demonstrated a favorable safety profile with no clinically relevant bleeding events. ConclusionsIntravenous and multiple subcutaneous dose administration of abelacimab were safe and well tolerated. The safety, PK, and PD data from these studies support the clinical development of abelacimab.

Cytotoxicity and Hemostatic One Step Green Synthesis of Iron Nanoparticles Coated with Green Tea for Biomedical Application

Heparin and its low molecular weight are anticoagulants that prevent the formation and extension of blood clots. However, these anticoagulant causes bleeding that takes longer to stop. Here, we explore using magnetic iron oxide (Fe3O4NPs) coated with green tea (GTPs) as a safe and effective nontherapeutic agent for blood clotting prevention. In this work, Magnetic iron oxide coated with green tea (GT@Fe3O4NPs) was successfully synthesized using a simple eco-friendly green method. Green tea is employed as a green reducing and stabilizing agent. We employed this method as a new low-cost and time-consuming route. Structural, blood biocompatibility and anticoagulant properties of the (GT@Fe3O4NPs) were analyzed. These analyses showed that the particles were of uniform shapes and sizes of 25 - 36 nm with a coating of GTPs. The vibrating sample magnetometer (VSM) measurement demonstrated a saturation magnetization of 4.90 emu/g with negligible coercivity and retentivity, indicating the superparamagnetic behavior of the GT@Fe3O4NPs at room temperature. The synthesized magnetic nanoparticles were highly stable and well-dispersed in an aqueous medium through their hydrophilic coating of GTPs. Cell viability and prothrombin time (PT) showed excellent blood compatibility in addition to promising anticoagulant ability, respectively. The work offers a novel, safe nanotherapeutic agent as a substitutional for heparin. As a result, GT@Fe3O4NPs can compete with heparin either in hemodialysis or the treatment of thromboembolic events as it can overcome related bleeding problems to a great extent. HIGHLIGHTS Magnetic iron oxide (Fe3O4 NPs) coated with green tea (GTPs) could be a safe substitutional of heparin, overcoming side effects of heparin such as bleeding Magnetic iron oxide (Fe3O4 NPs) coated with green tea (GTPs) can advance anticoagulant drugs by increasing control of the anticoagulant (e.g., decreasing the dose and reducing side effects while maintaining efficacy and increasing circulation) The new magnetic iron oxide (Fe3O4 NPs) coated with green tea (GTPs) anticoagulant drugs will profit patients undergoing high-risk surgical procedures and overcome anticoagulant-related bleeding problems to a great extent GRAPHICAL ABSTRACT

Gastrointestinal Bleeding: a Cardiologist's Point of View

Oral anticoagulant therapy is widely used in different patients for the prevention and treatment of thromboembolic events: in atrial fibrillation, deep vein thrombosis/pulmonary embolism, acute coronary syndrome, in the early postoperative period after orthopedic surgery. Nowadays it is possible to use vitamin K antagonists (warfarin) as well as direct oral anticoagulants (DOAC): dabigatran, rivaroxaban, apixaban and edoxaban. The mai complication of any anticoagulant therapy is bleeding (gastrointestinal, intracranial, etc.), which seriously limits its usage. In this review the incidence of gastrointestinal bleeding (GIB) associated with oral anticoagulants intake was analyzed according to the results of both large randomized and postregistration trials. Furthermore, the effect of age on the risk of GIB development is discussed, and also aspects of the pathophysiology of gastrointestinal mucosa lesions in patients taking DOAC are considered.

Spontaneous reports of adverse drug reactions related to oral anticoagulants in the Czech Republic.

Background Oral anticoagulants are established drugs of choice for the prevention and treatment of thromboembolic events. However, monitoring their safety remains warranted. Objective The aim was to analyze spontaneous reports of adverse drug reactions related to oral anticoagulants in the Czech Republic. Setting Retrospective observational pharmacovigilance study. Methods Adverse drug reaction reports were obtained from the State Institute for Drug Control between January 2005 and November 2017. Reports related to warfarin, dabigatran, apixaban, and rivaroxaban received from healthcare professionals and patients were analyzed. Main outcome measure Frequency and nature of adverse drug reactions reported to oral anticoagulants. Results In total, 297 reports containing 672 adverse drug reactions were received; 269 reports were sent by healthcare professionals (85% by physicians). In 65% of all reports, reactions were due to direct oral anticoagulants. A higher total number of adverse drug reactions was associated with direct oral anticoagulants than with warfarin [reporting odds ratio (ROR): 10.76; confidence interval (CI): 8.70-13.32; p < 0.001]. Along with the increasing utilization of direct oral anticoagulants, the reporting rate gradually declined over time, especially for rivaroxaban and apixaban. Fatal outcomes were reported in 7%, mostly for dabigatran. Hemorrhagic reactions were the most frequently reported adverse drug reactions (37% associated with dabigatran, 28% with apixaban, 24% with warfarin, and 23% with rivaroxaban), and compared to warfarin, they were significantly more often associated with direct oral anticoagulants (ROR: 14.36; CI: 9.57-21.54; p < 0.001). Conclusion The number of adverse drug reaction reports related to oral anticoagulants in the Czech Republic was relatively low, compared to other studies, but 96% of the cases were serious. Data from spontaneous adverse drug reactions reporting should be further analyzed in order to obtain additional information on the safety profile of oral anticoagulants.

Hemorrhagic Accidents to Vitamin K Antagonists: A Retrospective Study in the University Hospital of Casablanca

Oral anticoagulation based on anti-vitamin K is prescribed in the prevention and treatment of thromboembolic events, but it could bring up a significant hemorrhagic risk. This study aims at describing the epidemiological, clinical and evolutionary features of the hemorrhagic accidents to VKA. It is a retrospective descriptive study carried out at the Cardiology Department of Casablanca’s University Hospital of IbnRochd over a two-year period including 33 patients hospitalized for AVK-hemorrhagic accidents. Asymptomatic overdoses were excluded. In our sample the average age was 50 years with a sex ratio of 1.7 (21 Male/12 Female). There has been evidence of multi-morbid field of patients with several involved histories. Acenocoumarol was the prescribed molecule for all patients. Mechanical valve prostheses were the main indication of anticoagulant treatment (60%). More than half of patients were not regularly monitored. Polymedication was found in the majority of cases (78%), with an association with amiodarone in 20% of cases, and with anti-aggregation treatment in 10% of cases. Soft parts’ Hematomas and digestive hemorrhages were the most frequent forms of hemorrhagic accidents. Hemodynamic instability was found in two patients. The therapeutic conduct was different depending upon the case, but focused on stopping AVKs, administration of vitamin K, transfusion of blood cells and fresh frozen plasma. 86% of cases displayed a good evolution, with a mortality rate of 13% during the acute phase of the hemorrhagic accident. In conclusion, prevention of these accidents is the pillar of care, which puts forward the importance of informing and educating the various stakeholders in this potentially fatal iatrogenic complication. Considering the severity of bleeding under KVA, new direct oral anticoagulants may be a good alternative in some indications.

Prophylactic anticoagulants for people hospitalised with COVID-19.

Prophylactic anticoagulants for people hospitalised with COVID-19.

COVID-19 and Intensive Care

COVID-19 caused by SARS-CoV2 has spread rapidly across the world, resulting in many patients in need of intensive care support. Severe pneumonia, acute respiratory distress syndrome (ARDS), sepsis/septic shock, and multi-organ failure may occur during the disease course among many other complications. There still is not a definite cure, but supportive care is important to minimize complications. Patients in need of respiratory support and interventions should preferably be placed in negative pressure isolation rooms, with utmost care to decrease viral spread. Points to consider during oxygen therapy, non-invasive and invasive mechanical ventilation, and shock management of COVID-19 patients are discussed. Patients with mild hypoxia may be managed with conventional oxygen therapy, while others will benefit from high flow nasal oxygen therapy and mechanical ventilation. Although corticosteroids are not recommended for other viral pneumonia, there are recent reports suggesting that steroids may have a place in the treatment of COVID-19 patients with hypoxia. Shock may complicate the course of the disease and a search for the etiology of shock should be carefully planned. Thromboembolic events are common; prophylaxis and/or treatment of thromboembolic events should be managed according to the guidelines. Meanwhile, the results of ongoing randomized, controlled trials on antiviral and immunomodulatory agents are expected to offer better treatment options for COVID-19 patients in the near future.

Prevention and Treatment of Thromboembolic Events in Patients with Cancer: Advances and Challenges.

Prevention and Treatment of Thromboembolic Events in Patients with Cancer: Advances and Challenges.

Hemothorax: Rare Complication of VKA

Background: VKA-based oral anti-coagulation is widely used in the prevention and treatment of thromboembolic events, but which represents a significant bleeding risk. Hemothorax is a rare, life-threatening complication, conditioned by how quickly it is taken care of. Observation: 28 year old patient with a history of mechanical aortic valve prosthesis in 2012, on VKA, poorly monitored, admitted to an acute respiratory distress panel with a stable hemodynamic state, with a left pleural fluid effusion syndrome on clinical examination. The chest x-ray showed an opaque left hemithorax (Figure 1), with a large abundance of left pleural effusion on the chest ultrasound. On the biological assessment, the patient presented an incoagulable INR with anemia at 7g/dl. The therapeutic management was based on an emergency chest drainage which evacuated 1,500cc of hematic fluid, the administration of vitamin K and the transfusion in fresch frozen plasma and blood cell. The evolution has been favorable. Conclusion: The prevention of the occurrence of hemorrhagic accidents at VKA is the pillar of the management. Given the severity of the bleeding under VKA, the new direct oral anticoagulants may represent a good alternative in some indications.

Anticoagulants and Osteoporosis.

Anticoagulant agents are widely used in the treatment of thromboembolic events and in stroke prevention. Data about their effects on bone tissue are in some cases limited or inconsistent (oral anti-vitamin K agents), and in others are sufficiently strong (heparins) to suggest caution in their use in subjects at risk of osteoporosis. This review analyses the effects of this group of drugs on bone metabolism, on bone mineral density, and on fragility fractures. A literature search strategy was developed by an experienced team of specialists by consulting the MEDLINE platform, including published papers and reviews updated to March 2019. Literature supports a detrimental effect of heparin on bone, with an increase in fracture rate. Low molecular weight heparins (LMWHs) seem to be safer than heparin. Although anti-vitamin K agents (VKAs) have a significant impact on bone metabolism, and in particular, on osteocalcin, data on bone mineral density (BMD) and fractures are contrasting. To date, the new direct oral anticoagulants (DOACs) are found to safe for bone health.

SSRI co-medication with NOAC or VKA does not increase hospitalisation for bleeding: A retrospective nationwide cohort study in Austria 2010-2015.

ObjectivesNon‐vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) are used for the prophylaxis and treatment of thromboembolic events. A potential drug–drug interaction and increased bleeding events have been reported with co‐medication of selective serotonin receptor inhibitors (SSRIs) and VKA. The aim of this study was to investigate the bleeding risk of a coprescription of NOAC or VKA with SSRI.MethodsPatients with prescription of NOAC or VKA and an antidepressant drug therapy (ADTx) were selected from the drug reimbursement database of 13 Austrian health insurance funds. For this cohort, hospital discharge diagnoses for gastrointestinal bleeding, cerebral haemorrhage, and bleeding anaemia between 2010 and 2015 were analysed.ResultsData were available from 50 196 female and 31 308 male patients. Among these, 892 patients had 987 hospitalisations with bleeding events. The most frequent bleeding cases were gastrointestinal bleedings with 588 events (59.6%), followed by cerebral haemorrhage with 344 (34.8%), and bleeding anaemia with 55 events (5.6%), respectively. The risk of bleeding events was similar between SSRI and other ADTx, when combined with oral anticoagulants (p = 0.51). Concomitant treatment of patients with SSRI or other ADTx and NOAC was associated with an increased bleeding risk compared with cotreatment with VKA (1.21, 95% CI: 1.05‐1.40; p = 0.0097).ConclusionCo‐medication of SSRI with VKA or NOAC has little if any impact on hospital discharge diagnoses for bleeding events compared with cotreatment of those anticoagulants with other antidepressant medications.

Yeni oral antikoagülanlar

Oral anticoagulants are medications that have an important place in the prevention and treatment of thromboembolic events that can be seen in the course of many diseases today. Warfarin, vitamin K antagonists are the most commonly known and used oral anticoagulants. Drugs known as new oral anticoagulants have emerged due to the difficulties in treatment and follow-up with warfarin. New oral anticoagulants exhibit anticoagulant effects, disrupting the structure and function of some factors in the coagulation cascade. There are many advantages such as monitorisation requirement, constant dose use, patient compliance and ease of follow-up. Meta-analyzes of large studies with new oral anticoagulants have shown that they are non-inferior from warfarin in the prevention and treatment of thromboembolic events, and even superior in some cases. Due to the ease of use and advantages of these new agents, they have been rapidly spreading and taking place in the prevention and treatment of embolism and ischemic events. Therefore, the areas of use of these drugs, the location of treatment, follow-up, possible side effects and most importantly management of bleeding complications should be well known and applied.

Perioperative management of patients undergoing antithrombotic treatment in oral surgery in France: a survey

Introduction: The prevention and treatment of thromboembolic events is generally based on the prescription of antithrombotics. These drugs are associated with an increased hemorrhagic risk. The procedures for the management of patients under antithrombotic treatment are described in the recommendations of the Société Française de Chirurgie Orale (SFCO), published in 2015. The main objective of this study was to describe dentists' knowledge and practices regarding the perioperative management of patients under antithrombotic agents in oral surgery in France. Materials and methods: A national cross-sectional study was conducted between June and September 2018. An electronic questionnaire was created on Google Forms and sent through social networks. Results: In total, 185 responses were collected. Two-thirds of the respondents reported that they were aware of the 2015 recommendations. Ten respondents reported that they did not manage patients treated with antithrombotic drugs. Among the respondents who managed such patients, 25% and 16% ordered hemostasis tests for patients treated with direct anticoagulants and antiplatelet agents, respectively. Discussion: Although 71% of dentists considered themselves properly informed, one-third stated that they were not aware of SFCO's 2015 recommendations. Among those who were aware of these recommendations, 47% correctly ordered hemostasis tests before surgery in patients on antithrombotic medication. Conclusion: This study indicates that there is a lack of knowledge and noncompliance with the recommendations among at least half the sample population regarding perioperative management of patients on antithrombotic therapy.

Effect of gastroprotective agents on upper gastrointestinal bleeding in patients receiving direct oral anticoagulants

Objectives: Direct oral anticoagulants (DOACs) are effective in the prevention and treatment of thromboembolism; however, they are associated with upper gastrointestinal bleeding (UGIB). In this study, we evaluated the efficacy of gastroprotective agents (GPAs) in reducing the risk of UGIB in patients receiving DOACs.Methods: We retrospectively reviewed the medical records of 2076 patients who received DOACs for the prevention or treatment of thromboembolic events between January 2008 and July 2016. A cumulative incidence analysis using the Kaplan–Meier method was performed to determine the rate of UGIB and its association with GPAs administration.Results: Of the 2076 patients, 360 received GPAs. Over the follow-up period (1160 person-years), one patient in the GPA group (0.7 per 100 person-years) and 29 patients in the non-GPA group (2.8 per 100 person-years) developed UGIB (p = .189). In the multivariate analysis, UGIB was associated with older age (hazard ratio (HR), 1.041; p = .048), a history of peptic ulcer or UGIB (HR, 5.931; p < .001), and concomitant use of antiplatelet agents (HR, 3.121; p = .014). GPAs administration did not reduce the risk of UGIB (p = .289). However, based on the subgroup analysis of 225 patients with concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB, the GPA group (0 per 100 person-years) showed reduced incidence of UGIB compared with the non-GPA group (11.3 per 100 person-years) (p = .065).Conclusions: The prophylactic use of GPAs could reduce the risk of UGIB in patients receiving DOACs who have risk factors, such as concomitant use of antiplatelet agents or a history of peptic ulcer or UGIB.