Major Gastrointestinal Bleeding Research Articles

Comparative Effectiveness and Safety of Apixaban, Rivaroxaban, and Warfarin in Patients With Cirrhosis and Atrial Fibrillation : A Nationwide Cohort Study.

Apixaban, rivaroxaban, and warfarin have shown benefit for preventing major ischemic events, albeit with increased bleeding risk, among patients in the general population with atrial fibrillation (AF). However, data are scarce in patients with cirrhosis and AF. To compare the effectiveness and safety of apixaban versus rivaroxaban and versus warfarin in patients with cirrhosis and AF. Population-based cohort study. Two U.S. claims data sets (Medicare and Optum's de-identified Clinformatics Data Mart Database [2013 to 2022]). 1:1 propensity score (PS)-matched patients with cirrhosis and nonvalvular AF initiating use of apixaban, rivaroxaban, or warfarin. Primary outcomes included ischemic stroke or systemic embolism and major hemorrhage (intracranial hemorrhage or major gastrointestinal bleeding). Database-specific and pooled PS-matched rate differences (RDs) per 1000 person-years (PY) and Cox proportional hazard ratios (HRs) with 95% CIs were estimated, controlling for 104 preexposure covariates. Rivaroxaban initiators had significantly higher rates of major hemorrhagic events than apixaban initiators (RD, 33.1 per 1000 PY [95% CI, 12.9 to 53.2 per 1000 PY]; HR, 1.47 [CI, 1.11 to 1.94]) but no significant differences in rates of ischemic events or death. Consistently higher rates of major hemorrhage were found with rivaroxaban across subgroup and sensitivity analyses. Warfarin initiators also had significantly higher rates of major hemorrhage than apixaban initiators (RD, 26.1 per 1000 PY [CI, 6.8 to 45.3 per 1000 PY]; HR, 1.38 [CI, 1.03 to 1.84]), particularly hemorrhagic stroke (RD, 9.7 per 1000 PY [CI, 2.2 to 17.2 per 1000 PY]; HR, 2.85 [CI, 1.24 to 6.59]). Nonrandomized treatment selection. Among patients with cirrhosis and nonvalvular AF, initiators of rivaroxaban versus apixaban had significantly higher rates of major hemorrhage and similar rates of ischemic events and death. Initiation of warfarin versus apixaban also contributed to significantly higher rates of major hemorrhagic events, including hemorrhagic stroke. National Institutes of Health.

One-year effectiveness and safety outcomes of edoxaban treatment in Chinese patients with atrial fibrillation: First snapshot of more than 4,800 patients from the ETNA-AF-China study

Abstract Background Direct oral anticoagulants (DOACs) have become the first-line therapy for ischaemic stroke prevention in atrial fibrillation (AF) patients. Data on the effectiveness and safety of single DOAC in large Chinese populations are scarce. Purpose We firstly present the one-year outcome data of edoxaban treatment in 5001 Chinese AF patients. Methods This is a multi-centre, prospective, observational study, ETNA-AF-China, conducted in 89 centres from four economic regions in Mainland of China with a follow-up of two years. Primary endpoint of safety [bleeding events including intracranial hemorrhage (ICH), all-cause and cardiovascular (CV) mortality] and efficacy endpoints [stroke, systemic embolic events (SEE), transient ischemic attack (TIA)] were adjudicated. Annualised event rates and Kaplan­Meier (KM) survival curves are given. Results A total of 4822 patients (57.1% male) using edoxaban (60 mg OD: n=2614, 30 mg OD: n=2208) who completed one-year follow-up were included in the full analysis set. The mean (SD) age of the overall patient population was 70.3 (9.5) years, CHA2DS2-VASc and HAS-BLED scores were 2.9 (1.4), 1.7 (1.0), with creatinine clearance (CrCl) of 71.2 (27.7) mL/min. Patients receiving 30 mg OD edoxaban at baseline were older (73.4 vs 67.7 years), with higher CHA2DS2-VASc score (3.3 vs 2.6), larger percentage of frail (9.9% vs 3.4%), and higher renal impairment (defined as CrCl ≤80 mL/min, 70.3% vs 42.9%). Annualised rates for all-cause and cardiovascular death in the overall population were very low with 2.22%/year and 0.41%/year, respectively. (Figure 1) The death rates were nearly three times lower in those receiving standard dose (60 mg) than reduction dose (30 mg) of edoxaban. Annualised event rates for all stroke/SEE (1.03%/year) and ischemic stroke (0.60%/year) were similar between two dose groups. Overall, annualised rates for major bleeding (1.03%/year), ICH (0.18%/year), major gastrointestinal (GI) bleeding (0.48%/year) events were relatively low, and those on 60 mg dose experienced less above bleeding events. Cumulative survival analysis demonstrated a slow increase in time-to-first event curve of all-cause death; and from baseline to 1-year follow-up, significant lower events of all-cause death (log-rank p<0.001), major bleeding (p=0.002) in 60 mg vs 30 mg edoxaban groups. (Figure 2). Conclusion Low incidences of major bleeding, notably ICH, major GI bleeding, and CV death were observed in unselected 4822 patients with AF during 1-year of edoxaban treatment. These findings confirm the effectiveness and safety of routine edoxaban use in China, consistent with other countries, and reinforce the results of the ENGAGE AF-TIMI 48 trial.Figure 1Figure 2

#688 Major gastrointestinal bleeding in dialysis: influence of age, sex, race & comorbidities

Abstract Background and Aims Gastrointestinal bleeding (GIB) is considered the most common type of bleeding event in the dialysis population [1]. However, studies to date are small and not representative of the dialysis population, and the influence of patient characteristics has not been considered. We used a nationally representative sample of dialysis patients treated in the United States (US) to characterize the rates of major GIB episodes requiring hospitalization overall and by age, sex, race, and history of GIB comorbidity. Method We used data from a kidney care network from Jan 2018 through Mar 2021. We included data from adult dialysis patients (age ≥18 years) who were treated with dialysis for at least 30 days. We excluded patients who started dialysis on or after Jan 2021 to provide a three-month minimum follow up time for outcomes to occur. GIB hospitalizations were identified from international classification of diseases (ICD) diagnosis codes recorded as the primary, secondary, or tertiary discharge reason for hospitalization. ICD clusters defining GIB hospitalizations and lesion location were based on the US Healthcare Cost and Utilization Project [2]. We calculated proportion of patients with one or more GIB hospitalization, and the proportion of GIB observations per patient during the 3.25-year period by patient characteristics (GIB comorbidity, sex, age, race). Results Among 366,839 adult dialysis patients, 6.8% (n = 25,057) experienced one or more GIB hospitalization during the 3.25-year period. In total, there were 36,791 GIB hospitalization observations with 73.5% (n = 18,422) of patients with one GIB hospitalization, 16.8% (n = 4208) with two GIB hospitalizations, and 9.7% (n = 2,427) with three or more GIB hospitalizations. The lesion location was unspecified in diagnosis codes for 64.7% (n = 23,576) of GIB hospitalization observations. Among GIB hospitalization observations with a recorded lesion location, 60.3% (n = 7,968) were an upper GIB and 39.7% (n = 5,247) were a lower GIB. A baseline history of a GIB comorbidity was associated with a 2.9-fold higher rate for the occurrence of one or more GIB hospitalization in a unique patient, and a 3.5-fold higher rate of a GIB hospitalization event considering all observations (Fig. 1A). GIB hospitalization rates were relatively consistent between females and males on both a patient- and observation-level (Fig. 1B). There were positive increases in GIB hospitalization rates with older age categories, with about a 2-fold higher rate among those with an age ≥75 years compared to an age 18-44 years on both a patient- and observation-level (Fig. 2A). GIB hospitalization rates were relatively consistent for race groups, albeit there may be a trend for slightly higher rates among those with a black race, in particular on an observation level that accounts for multiple events per patient (Fig. 2B). Conclusion Major GIB events requiring hospitalization affect about 7% of dialysis patients. It appears about 60% of GIB hospitalizations were for an upper GIB, and about 40% were for a lower GIB. Patients who experienced one GIB hospitalization commonly had multiple GIB events, with more than 25% having two or more GIB hospitalizations during the observation period. Older age and a history of a baseline GIB comorbidity were associated with higher GIB hospitalization rates. Biological sex and race did not appear to be associated to GIB hospitalization rates. Ongoing analysis of GIB incidence accounting for person-years at risk is needed to confirm these observations.

#2067 Prediction of gastrointestinal bleeding hospitalization risk in hemodialysis using machine learning techniques

Abstract Background and Aims INitiativeS on advancing Patients’ outcomes In REnal disease (INSPIRE) is an academia and industry collaboration set forth to identify critical investigations needed to advance the practice of medicine in nephrology. Gastrointestinal bleeding (GIB) is one of the most common types of bleeding events in the kidney dialysis population [1]. We aimed to develop a model to predict GIB hospitalization risk in a hemodialysis (HD) patient within 180 days. We evaluated advanced machine learning algorithm (XGBoost) and compared it to traditional machine learning algorithm (logistic regression) modeling techniques. Method We used data from a kidney care network from 2017 through 2020. We included data from adult dialysis patients (age ≥18 years). GIB related hospitalization was defined based on international classification of diseases (ICD) diagnosis codes recorded as the primary, secondary, or tertiary discharge reason for hospitalization. Two distinct models were created using XGBoost and logistic regression algorithms and using the same dataset. Both models were evaluated using metrics such as area under the receiver operating curve (AUROC), accuracy, sensitivity, and specificity. Missing data was imputed using mean for quantitative data and mode for qualitative data. The dataset then was randomly divided into 60% training, 20% validation and 20% test dataset. The test data, comprising unseen patients and data was used to evaluate the performance of the model. This means that the model had never encountered the test data during its learning phase, which included training the model and then validating the model. Results The incidence of 180-day GIB hospitalization was 1.12% in the HD population (n = 5 116 with GIB hospitalization/ n = 451 653 without GIB hospitalization), and consistent in the unseen test dataset (n = 465 with GIB hospitalization/ n = 38586 without GIB hospitalization). The XGBoost model showed higher predictive performance compared to logistic regression (Table). The AUROC was 0.72 (95% confidence interval (CI) 0.69, 0.74) for the XGBoost model. In comparison, the AUROC was 0.615 (95% CI 0.60, 0.64) for the logistic regression model. Specificity was 67% versus 58% for the XGBoost model versus logistic regression model respectively. However, sensitivity for both the models was 65%. The top predictors for major GIB were consistent in both models for many factors, yet some factors showed different importance on outcome prediction (Fig. 1). Higher risk of GIB hospitalization was associated with older age, lower ferritin levels, and recent all-cause hospitalizations in both models. The XGBoost showed high importance on outcome prediction for lower hemoglobin and higher serum 25 hydroxy (25OH) vitamin D values, and the logistic regression model showed high importance for higher amounts of saline delivered during an HD treatment and lower intact parathyroid hormone (iPTH) levels. Conclusion We found advanced machine learning prediction modeling (XGBoost) appears suitable for identifying a HD patient at risk for a GIB hospitalization in the next 180 days, and outperforms traditional machine learning (logistic regression) modeling techniques. Although both models showed identical sensitivity, the XGBoost model had higher specificity. Prospective testing is needed to confirm the model's performance. The association between bone mineral metabolism markers and GIB hospitalization risk is unexpected and warrants further investigation.

Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year data from the ETNA-AF-Europe study

BackgroundTo assess long-term effectiveness and safety of edoxaban in Europe. Methods and resultsETNA-AF-Europe, a prospective, multinational, multi-centre, post-authorisation, observational study was conducted in agreement with the European Medicines Agency. The primary and secondary objectives assessed real-world safety (including bleeding and deaths) and effectiveness (including stroke, systemic embolic events and clinical edoxaban use), respectively.Median (interquartile range) age of the 13,164 patients was 75.0 (68.0–80.0) years; CHA2DS2-VASc and HAS-BLED scores were 3.0 (2.0–4.0) and 2.0 (1.0–2.0), respectively. Follow-up duration was 3.98 (3.21–4.05) years. Patients on edoxaban 30 mg (n = 3042) at baseline were older (80.0 vs 73.0 years), more likely assessed as frail by investigators (27.0% vs 6.6%) and had more comorbidities than those on edoxaban 60 mg (n = 9617; missing dosing information for n = 505). Annualised event rates of all-cause and cardiovascular death in the overall population, edoxaban 60 mg and edoxaban 30 mg groups were 4.1%, 2.8% and 8.4%, and 1.0%, 0.7% and 2.0%, respectively. Annualised rates of stroke were relatively constant throughout the follow-up, transient ischaemic attack and systemic embolism were < 1% in the overall population. Rates of any major and major gastrointestinal bleeding were low, with slightly higher rates for edoxaban 30 vs 60 mg group. Intracranial haemorrhage was uncommon (0.2%). ConclusionsIn European patients with AF, long-term therapy with edoxaban is associated with low and relatively constant annualised rates of stroke and major bleeding. Differences in outcomes between the two approved doses are attributable to differences in clinical characteristics.

Development and Application of an Attribute-Based Taxonomy on the Benefits of Oral Anticoagulant Switching in Atrial Fibrillation: A Delphi Study.

Patients with atrial fibrillation (AF) often switch between oral anticoagulants (OACs). It can be hard to know why a patient has switched outside of a clinical setting. Medication attribute comparisons can suggest benefits. Consensus on terms and definitions is required for inferring OAC switch benefits. The objectives of the study were to generate consensus on a taxonomy of the potential benefits of OAC switching in patients with AF and apply the taxonomy to real-world data. Nine expert clinicians (seven clinical pharmacists, two cardiologists) with at least 3years of clinical and research experience in AF participated in a Delphi process. The experts rated and commented on a proposed taxonomy on the potential benefits of OAC switching. After each Delphi round, ratings were analyzed with the RAND Corporation/University of California, Los Angeles (RAND/UCLA) appropriateness method. Median ratings, disagreement index, and comments were used to modify the taxonomy. The resulting taxonomy from the Delphi process was applied to a cohort of patients with AF who switched OACs in a population-based administrative health dataset from 1996 to 2019 in British Columbia, Canada. The taxonomy was finalized in two Delphi rounds, reaching consensus on five switch benefit categories: safety, effectiveness, convenience, economic considerations, and drug interactions. Safety benefit (a switch that could lower the risk of adverse drug events) had three subcategories: major bleeding, intracranial hemorrhage (ICH), and gastrointestinal (GI) bleeding. Effectiveness benefit had four subcategories: stroke and systemic embolism (SSE), ischemic stroke, myocardial infarction (MI), and all-cause mortality. Real-world OAC switches revealed that more OAC switches had convenience (72.6%) and drug interaction (63.0%) benefits compared to effectiveness (SSE 22.0%, ischemic stroke 11.1%, MI 3.1%, all-cause mortality 10.1%), safety (major bleeding 24.3%, GI bleeding 10.6%, ICH 48.5%), and economic benefits (12.1%). The Delphi-based taxonomy identified five criteria for the beneficial effects of OAC switching, aiding in characterizing real-world OAC switching.

The Role of Direct Oral Anticoagulants in the Treatment of Cancer-Associated Venous Thromboembolism: Review by Middle East and North African Experts.

Venous thromboembolism is a leading cause of morbidity and mortality in patients with active cancer who require anticoagulation treatment. Choice of anticoagulant is based on careful balancing of the risks and benefits of available classes of treatment: vitamin K antagonists, low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs). Results from randomized controlled trials have shown the consistent efficacy of DOACs versus LMWH in the treatment of cancer-associated venous thromboembolism (VTE). However, increased major gastrointestinal bleeding was observed for edoxaban and rivaroxaban, but not apixaban, compared with LMWH dalteparin. Most guidelines recommend DOACs for the treatment of cancer-associated VTE in patients without gastrointestinal or genitourinary cancer, and with considerations for renal impairment and drug-drug interactions. These updates represent a major paradigm shift for clinicians in the Middle East and North Africa. The decision to prescribe a DOAC for a patient with cancer is not always straightforward, particularly in challenging subgroups of patients with an increased risk of bleeding. In patients with gastrointestinal malignancies who are at high risk of major gastrointestinal bleeds, apixaban may be the preferred DOAC; however, caution should be exercised if patients have upper or unresected lower gastrointestinal tumors. In patients with gastrointestinal malignancies and upper or unresected lower gastrointestinal tumors, LMWH may be preferred. Vitamin K antagonists should be used only when DOACs and LMWH are unavailable or unsuitable. In this review, we discuss the overall evidence for DOACs in the treatment of cancer-associated VTE and provide treatment suggestions for challenging subgroups of patients with cancer associated VTE.

Effectiveness and Safety of Different Oral Anticoagulants with P-glycoprotein/ CYP3A4 Inhibitors: A Network Meta-analysis.

Metabolism of oral anticoagulants (OAC) is affected by P-glycoprotein (P-gp)/ CYP3A4 enzyme. However, the P-gp/CYP3A4 inhibitors are unavoidably used with OACs. Medline, Cochrane, and Embase were systematically searched for randomized controlled trials and cohort studies from inception till 23rd November, 2022 to assess the safety and effectiveness of OACs when concomitantly used with P-gp/CYP3A4 inhibitors. The primary outcomes were major bleeding and gastrointestinal (GI) bleeding. Secondary outcomes were stroke/systemic embolism (SE), all-cause mortality, any bleeding as well as intracranial hemorrhage (ICH). We estimated summary odds ratios (OR) with 95% credible intervals (CI) using pairwise and network meta-analysis with random effects. A total of 11 studies involving 37,973 patients were included. When concomitantly used with P-pg/ CYP3A4 inhibitors, network meta-analysis indicated that dabigatran, apixaban, and edoxaban were associated with significantly lower risk of major bleeding compared to rivaroxaban, with ORs of 0.56, 0.51 and 0.48, respectively. Rivaroxaban and dabigatran were associated with a significantly increased risk of GI bleeding than warfarin, apixaban and edoxaban. Dabigatran and apixaban were linked with significantly lower risk of any bleeding compared with warfarin (ORs were 0.75 and 0.68, respectively) or rivaroxaban (ORs were 0.67 and 0.60, respectively). Apixaban (OR 0.32) and edoxaban (OR 0.35) were associated with a lower risk of ICH compared with warfarin. There was no difference between any OACs in terms of stroke/SE or all-cause mortality. When concomitantly used with P-gp/CYP3A4 inhibitors, apixaban and edoxaban were associated with a lower risk of bleeding, though no significant difference in effectiveness was observed among all OACs.

Aetiology and predictors of major bleeding events in patients with heart failure with reduced ejection fraction undergoing percutaneous coronary intervention

ObjectivesWe sought to determine the relationship between the degree of left ventricular ejection fraction (LVEF) impairment and the frequency and type of bleeding events after percutaneous coronary intervention (PCI).DesignThis was...

Clinical Characteristics and Incidence of Hemorrhagic Complications in Patients Taking Factor Xa Inhibitors in Spain: A Long-Term Observational Study.

Objective. To analyze the clinical characteristics of patients taking Factor Xa inhibitors (FXai), either direct FXai or enoxaparin (only in active cancer patients), and to estimate the incidence of and risk factors for major bleeding during FXai use. Methods. A retrospective cohort study, which included secondary data from computerized health records of primary care centers and hospitals in seven Spanish Autonomous Communities. Results. 9374 patients were analyzed, with 8972 taking direct FXai and 402 enoxaparin. At baseline, the mean age (SD) was 71.8 (9.4) years, 56.0% were women, 76.3% had hypertension, 33.6% had type 2 diabetes, and 25.5% had heart failure. The most common indication for FXai use was atrial fibrillation (72.3%), followed by venous thromboembolism (22.2%) and non-mechanical cardiac-valve replacement (5.6%). At the end of the follow-up period, the incidence rates of major bleeding overall, gastrointestinal, and intracranial were 10.2, 9.0, and 0.8 per 100 person-years, respectively. The total incidence of fatal major bleeding was 0.5 per 100 person-years. Incidence rates of all bleedings progressively decreased over time, with 62.5% of the first events occurring in the initial three months and reaching 76.8% within six months following initiation of treatment. Only 4.8% of the 1st major bleedings led to death, 2.3% in the case of major gastrointestinal bleeding, and 30.8% after an intracranial bleeding. 65.9% of patients discontinued anticoagulation after experiencing major bleeding. Conclusions. In Spain, patients taking FXai were old and had many comorbidities. Despite incidence rates of major bleeding were high, incidence rates of intracranial and fatal bleedings were low, but more efforts are required due to their relevant clinical impact.

A284 EVALUATING THE INCIDENCE OF MAJOR GASTROINTESTINAL BLEEDING IN PATIENTS WITH CIRRHOSIS ON ANTICOAGULATION THERAPY: A TERTIARY SINGLE CENTRE EXPERIENCE

Abstract Background Patients with chronic liver disease, especially those with cirrhosis, face an increased risk of bleeding and thrombosis due to hemostasis dysregulation. In such cases, prescribing anticoagulation therapy requires a cautious approach, given the inherent risk-reduction in thrombosis alongside a suspected elevated bleeding risk. Aims Perform a retrospective study to evaluate anticoagulation safety and gastrointestinal bleeding incidence in cirrhotic patients. Methods A retrospective study was conducted at the University Hospital of London Health Sciences Centre, involving patients who attended outpatient hepatology clinics between 2010 and 2022. To be eligible, patients had to be 18 years or older and have confirmed cirrhosis through imaging, radiology, or pathology. They were monitored for up to 5 years for the primary outcome, which was major gastrointestinal bleeding requiring hospitalization. Exclusions included patients with underlying hematologic or thrombotic conditions contributing to abnormal hemostasis beyond cirrhosis and those who underwent liver transplantation. Descriptive statistics were provided, such as means and standard deviations for continuous variables, and proportions/percentages for categorical ones. Group comparisons utilized the Student's t-test for continuous variables and chi-squared tests for categorical variables. Univariate and multivariate logistic regression were employed to calculate odds ratios and their associated 95% confidence intervals for the primary outcome Results We retrospectively enrolled 300 patients, with 34.0% having cirrhosis and anticoagulation history. The average age was 63.1 years [95% CI 61.7 – 64.6], and 43.7% were female. Atrial fibrillation was the primary reason for anticoagulation (53.9%). Cirrhotic patients on anticoagulation had a 13.1% bleeding rate, while those without had 18.6% (p-value = 0.207, not significant). Univariate analysis suggested a possible link between anticoagulation and bleeding risk (OR 1.51 [95% CI 0.79 – 2.89]). No covariates predicted bleeding in univariate logistic regression. In multivariate analysis adjusting for age and sex, the odds ratio remained at 1.50 [95% CI 0.78 – 2.88]. The study hints at a higher bleeding risk in cirrhotic patients on anticoagulation, but more statistical power is needed, either through a larger sample or a multicenter approach. Conclusions To further investigate the association between anticoagulation and bleeding risk in cirrhotic patients, a larger multicentre study with increased enrollment is required. Nonetheless, interim findings do suggest the potential existence of an associated bleeding risk in cirrhotic patients undergoing anticoagulation therapy, albeit with a small observed effect size and uncertain clinical significance. Funding Agencies None

State-of-the-Art of Transcatheter Left Atrial Appendage Occlusion.

Left atrial appendage occlusion (LAAO) is an increasingly used alternative to oral anticoagulation in patients with atrial fibrillation, especially in patients with absolute/relative contraindications to these therapies. This review will cover three main aspects of the procedure. In the fist part of the manuscript, we focus on patient selection. We describe three main categories of patients with primary indication to LAAO, namely patients with previous or at a high risk of intracerebral bleeding, patients with a history of major gastrointestinal bleeding and patients with end-stage renal disease and absolute contraindication to novel oral anticoagulants. Some other potential indications are also described. In the second part of the manuscript, we review available devices, trying to highlight different aspects and potential specific advantages. The last section overviews different ways for pre-, intra- and postprocedural imaging, in order to improve procedural safety and efficacy and ameliorate patient outcome. The characteristics of available contemporary devices and the role of imaging in procedural planning, intraprocedural guidance and follow-up are described.

Dispensing pharmacy chains and direct anticoagulants: Potential associations with patient outcomes.

Pharmacy chains can differ with respect to the characteristics of their patient populations as well as their nonprescription products, services, and practices, and thus may serve as a surrogate for potential unmeasured confounding in observational studies of prescription drugs. This study evaluates whether a single-source drug can have different patient outcomes based on the dispensing pharmacy chain. Separate analyses for two anticoagulant drugs, rivaroxaban and apixaban, were conducted using Medicare Fee-for-Service claims evaluating the association between dispensing pharmacy chain and outcomes of acute myocardial infarction, ischemic stroke, intracranial hemorrhage, gastrointestinal (GI) bleeding, all-cause mortality, and major GI bleeding. Inverse probability of treatment weighting (IPTW) was used to balance baseline covariates across pharmacy chain cohorts, and outcome association was assessed with a Cox Proportional Hazards model. We observed no differences in outcomes across pharmacy chains for apixaban recipients. Rivaroxaban recipients from pharmacy chain C, however, had lower rates of GI bleeding (adjusted HR 0.83; 95% CI 0.69-1.00) and ischemic stroke (adjusted HR 0.57; 95% CI 0.38-0.87) as compared to chain A in primary analyses with a 3-day grace period. The results moved closer to the null when 14- and 30-day grace periods were implemented. These results suggest that dispensing pharmacy chains may have the potential to act as a confounder of associations between drug exposure and outcome in some observational studies. Additional studies of potential confounding by pharmacy chain are needed. Further evaluation of potential pharmacy chain effects on safe use would be of value.

Bleeding Risk Prediction in Patients Treated with Antithrombotic Drugs According to the Anatomic Site of Bleeding, Indication for Treatment, and Time Since Treatment Initiation.

Background Reasons for the relatively poor performance of bleeding prediction models are not well understood but may relate to differences in predictors for various anatomical sites of bleeding. Methods We pooled individual participant data from four randomized controlled trials of antithrombotic therapy in patients with coronary and peripheral artery diseases, embolic stroke of undetermined source (ESUS), or atrial fibrillation. We examined discrimination and calibration of models for any major bleeding, major gastrointestinal (GI) bleeding, and intracranial hemorrhage (ICH), according to the time since initiation of antithrombotic therapy, and indication for antithrombotic therapy. Results Of 57,813 patients included, 1,948 (3.37%) experienced major bleeding, including 717 (1.24%) major GI bleeding and 274 (0.47%) ICH. The model derived to predict major bleeding at 1 year from any site (c-index, 0.69, 95% confidence interval [CI], 0.68-0.71) performed similarly when applied to predict major GI bleeding (0.71, 0.69-0.74), but less well to predict ICH (0.64, 0.61-0.69). Models derived to predict GI bleeding (0.75, 0.74-0.78) and ICH (0.72, 0.70-0.79) performed better than the general major bleeding model. Discrimination declined over time since the initiation of antithrombotic treatment, stabilizing at approximately 2 years for any major bleeding and major GI bleeding and 1 year for ICH. Discrimination was best for the model predicting ICH in the ESUS population (0.82, 0.78-0.92) and worst for the model predicting any major bleeding in the coronary and peripheral artery disease population (0.66, 0.65-0.69). Conclusion Performance of risk prediction models for major bleeding is affected by site of bleeding, time since initiation of antithrombotic therapy, and indication for antithrombotic therapy.

Acute respiratory failure prognosis in prolonged ICU stays

Objective: This study aimed to assess the outcome of patients with acute respiratory failure and need of mechanical ventilation who stayed for more than 21 days in the ICU. Methods: All acute respiratory failure patients in King Saud Medical City, Riyadh Saudi Arabia and adults ICU who required a lengthy intensive care unit stay of more than 21 days between January 2022 and August 2023 were identified in this retrospective study. Information was extracted from the hospital database by trained physicians. Results: Total 121 patients (mean age 61.2±15.8 years) were included. Of which, 24.1% patients were more than 70 years. Sepsis was the most common cause of prolonged ICU stay both in survivors and non-survivors with 77.8% and 76.1%, respectively. Compared to patients who survived, non-survivors had higher acute physiology and chronic health evaluation (APACHE 4) scores were considerably older. Moreover, non-survivors were more likely than survivors to have renal failure, arrhythmia, hepatic failure, or significant gastrointestinal tract bleeding as reasons for a lengthy ICU stay. Patients who were admitted to ICU because they needed further surgery were more likely to survive. Conclusion: When acute respiratory fever (ARF) patients needed a lengthy stay in the ICU, their prognosis was not good. A high risk of in-hospital death was linked to older ages, more than 28 days ICU stay, more than 25 APACHE 4 score, unstable hemodynamic condition, hepatic failure, renal failure, major gastrointestinal tract bleeding, and needing FiO2 &amp;ge;40%.

Daily low-dose aspirin and incident type 2 diabetes in community-dwelling healthy older adults: a post-hoc analysis of efficacy and safety in the ASPREE randomised placebo-controlled trial

Inflammation has been implicated in the pathogenesis of diabetes. This study investigated the randomised treatment effect of low-dose aspirin on incident type 2 diabetes and fasting plasma glucose (FPG) concentrations among older adults. ASPREE was a double-blind, placebo-controlled trial of daily oral low-dose aspirin. The study population included community-dwelling individuals aged 70 years or older (≥65 years for US minority ethnic groups) in the USA and Australia who were free of cardiovascular disease, independence-limiting physical disability, or dementia. For the post-hoc analysis, we excluded participants with diabetes at baseline or with incomplete or missing incident diabetes data during follow-up. Participants were randomly assigned 1:1 to oral 100 mg daily enteric-coated aspirin or placebo. Incident diabetes was defined as self-reported diabetes, commencement of glucose-lowering medication, or a FPG concentration of 7·0 mmol/L or more assessed at annual follow-up visits among participants with no diabetes at baseline. We used Cox proportional hazards models and mixed-model repeated measures to assess the effect of aspirin on incident diabetes and FPG concentrations in the intention-to-treat population. We assessed major bleeding in participants who had taken at least one dose of study medication. Between March 10, 2010, and Dec 24, 2014, a total of 16 209 participants were included (8086 [49·9%] randomly assigned to aspirin and 8123 [50·1%] randomly assigned to placebo). During a median follow-up of 4·7 years (IQR 3·6-5·7), 995 (in 6·1% individuals) incident cases of type 2 diabetes were recorded (459 in the aspirin group and 536 in the placebo group). Compared with placebo, the aspirin group had a 15% reduction in risk of incident diabetes (hazard ratio 0·85 [95% CI 0·75 to 0·97]; p=0·013) and a slower rate of increase in FPG concentration at year 5 (between-group difference estimate -0·048 mmol/L [95% CI -0·079 to -0·018]; p=0·0017). Major bleeding (major gastrointestinal bleeding, intracranial bleeding, and clinically significant bleeding at other sites) occurred in 510 (3·2%) of 16 104 participants (300 [3·7%] in the aspirin group and 210 [2·6%] in the placebo group). Compared with placebo, the aspirin group had a 44% increase in risk of major bleeding (hazard ratio 1·44 [95% CI 1·21 to 1·72]; p<0·0001). Aspirin treatment reduced the incidence of type 2 diabetes and slowed the increase in FPG concentration but increased major bleeding among community-dwelling older adults. Given the increasing prevalence of type 2 diabetes among older adults, the potential for anti-inflammatory agents such as aspirin to prevent type 2 diabetes or improve glucose levels warrants further study with a comprehensive assessment of all potential safety events of interest. US National Institute on Aging, US National Cancer Institute, National Health and Medical Research Council of Australia, Monash University, and the Victorian Cancer Agency.

Association between subconjunctival hemorrhage and hemorrhagic disorders: a nationwide population-based study

Subconjunctival hemorrhage (SCH) is a benign eye condition that is often noticeable and leads to medical attention. Despite previous studies investigating the relationship between SCH and cardiovascular diseases, the relationship between SCH and bleeding disorders remains controversial. In order to gain further insight into this association, a nationwide cohort study was conducted using data from the National Health Insurance Service-National Sample Cohort version 2.0 from 2006 to 2015. The study defined SCH using a diagnostic code and compared the incidence and risk factors of intracerebral hemorrhage (ICH) and gastrointestinal (GI) bleeding in 36,772 SCH individuals and 147,088 propensity score (PS)-matched controls without SCH. The results showed that SCH was associated with a lower risk of ICH (HR = 0.76, 95% CI = 0.622–0.894, p = 0.002) and GI bleeding (HR = 0.816, 95% CI = 0.690–0.965, p = 0.018) when compared to the PS-matched control group. This reduced risk was more pronounced in females and in the older age group (≥ 50 years), but not observed in males or younger age groups. In conclusion, SCH dose not increase the risk of ICH and major GI bleeding and is associated with a decreased incidence in females and individuals aged ≥ 50 years.

EGS P22 Prophylactic PPIs in NOF Fractures to prevent UGI bleed- Can It Be a Lifesaving Intervention?

Abstract Background Assess the incidence of UGI bleed in patients with NOF fractures. Develop trust-based guidelines to include PPIs in the management of such patients. Methods A total of 119 patients who were admitted with NOF fractures between January and March 2022 were included. All the patients admitted to RAEI with NOF fractures were included in the study. All the patients with a previous diagnosis of GORD, peptic ulcers, or perforated peptic ulcers and those who were already taking PPIs before admission were excluded from the study. Information was collected about the hospital number, age, gender and if there was any gastrointestinal bleeding was noticed in such patients during the hospital admission. Results Our results showed that most of the patients who were admitted with NOF fractures were elderly. A total of 5/119 patients had major gastrointestinal bleeding during there hospital admission thus warranting further procedures such as endoscopy, transfusions, and prolonged hospital stay. Conclusions Elderly patients with NOF fractures are at an increased risk of stress-related mucosal damage and subsequent UGIB. Due to the devastating and potentially threatening complications of mucosal damage, preventative measures are mandatory. Therefore, PPIs should a routine part of drug prescription in patients admitted with NOF fractures. This can not only help prevent this potential bleeding but can also be cost-effective in terms of preventing prolonged stays and readmissions. A reaudit is planned to be done in 1 month's time after the implementation of the changes.

Clinical outcomes in patients receiving oral anticoagulation stratified by the presence of dose reduction criteria and older age: a subanalysis of ENVISAGE-TAVI AF

Abstract Background/Introduction In the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation–Atrial Fibrillation) trial, edoxaban (EDX) was noninferior to vitamin K antagonists (VKAs) for preventing most adverse clinical events but was associated with increased major bleeding (MB). Presence of EDX dose reduction criteria applied in the trial (DRC; body weight ≤60 kg, CrCL 15–50 mL/min, concomitant use of selected P-glycoprotein-inhibitors) indicates a more vulnerable patient phenotype. Purpose Compare clinical outcomes after TAVI for AF patients with and without DRC stratified by anticoagulation strategy and age. Methods ENVISAGE-TAVI AF (NCT02943785) was a multicentre, open-label, randomised, controlled trial comparing EDX vs VKA in patients with AF as the indication for oral anticoagulation (OAC) after successful TAVI. In this analysis, outcomes—which included net adverse clinical events (NACE; composite all-cause death, myocardial infarction, ischaemic stroke, systemic thromboembolic event, valve thrombosis, or MB), intracranial haemorrhage, ischaemic stroke, all-cause death, cardiovascular (CV) death, non-CV death, MB bleeding, fatal MB bleeding, and major gastrointestinal bleeding (MGIB) —were compared in patients with vs without DRC, further stratified by OAC use, and age (&amp;lt; or ≥80 years [y]). Results Patients meeting DRC (n=637) were older, more often female, and had lower baseline CrCL than those without (n=740). In addition, these patients had significantly higher rates of NACE (P=0.0375) and all-cause death (P=0.0136). There were no differences in MB or MGIB rates between patients with vs without DRC. EDX resulted in more MB (hazard ratio [95% CI], 1.6 [1.1–2.5] and MGIB (2.6 [1.2–5.8]) than VKA only in patients without DRC. In patients aged &amp;lt;80 y meeting DRC, rates of all-cause death (P=0.0366) and CV death (P=0.0042) were significantly higher than those without DRC. Among patients aged &amp;lt;80 y, there were no differences in rates of clinical outcomes between EDX and VKA regardless of the presence or absence of DRC; Figure 1). In patients aged ≥80 y, there were no differences in rates of all-cause death, MB, or MGIB in those with or without DRC; Figure 2). Additionally in this age group, there was no difference in MB between patients on EDX and VKA both with and without DRC. However, there was more MGIB with EDX when there were no DRC. In patients aged ≥80 y with DRC, all-cause death was lower with EDX. Conclusions In this subanalysis of ENVISAGE-TAVI AF, the presence of DRC indicates a more vulnerable patient phenotype at higher risk for all-cause death after TAVI and in whom a lower EDX dose may have substantial benefits in terms of outcomes, including bleeding events, particularly in patients ≥80 y.Figure 1Figure 2

Risk and benefits of baseline antiplatelet therapy in 58,598 patients with atrial fibrillation randomized to NOACs vs warfarin

Abstract Background The efficacy and safety of NOAC versus warfarin (W) may differ in AF pts receiving antiplatelet therapy (APT) at baseline. Moreover, prior individual trial-specific analyses examining the treatment effect of NOAC vs. W as a function of APT are underpowered for interaction testing. Purpose We evaluated outcomes by randomized anticoagulant stratified by baseline APT in a pooled individual pt-level meta-analysis of 4 pivotal RCTs of NOAC vs. W in AF: RE-LY, ROCKET-AF, ARISTOTLE, and ENGAGE AF-TIMI 48. Methods Pts were stratified by use of APT vs. no APT at baseline. Pts randomized to low-dose NOAC not globally approved (edoxaban 30/15 mg or dabigatran 110 mg) were excluded. The primary efficacy and safety outcomes were stroke/systemic embolic events (S/SEE) and major bleeding, respectively; ischemic stroke (IS), intracranial hemorrhage (ICH), major GI bleeding and all-cause mortality (ACM) were secondary outcomes. Each outcome was assessed by randomized treatment using a Cox model stratified by trial with adjustment for age, sex, weight, CrCl, smoking status, HTN, DM, CAD, prior MI, PAD, and prior stroke. Interaction testing was performed by APT at baseline. Results Of 58,598 pts, 19,774 (34%) were on APT at baseline (92% aspirin only, 5% P2Y12 only, 3% DAPT). Pts treated with APT had greater prevalence of CAD (41% vs. 24%), prior MI (22% vs. 11%), and PAD (6% vs. 4%) (p&amp;lt;0.001 for each). Reflective of these baseline differences, the annualized event rate for each outcome was higher in the APT vs. no APT group (Figure). The treatment effect (HR) of NOAC vs. W for all 6 clinical outcomes was consistent irrespective of baseline APT (p-interaction [aHR] for each = NS; Figure). However, the absolute risk reduction (ARR) for NOAC vs. W differed for ICH and major GI bleeding as a function of baseline APT (Figure). Specifically, for ICH, a greater absolute benefit was seen with NOAC vs. W in those on APT at baseline (ARR 0.6% vs. 0.3%; p-int = 0.007). Conversely, for major GI bleeding, NOAC vs. W was associated with greater absolute risk in those on APT (ARR -0.6% vs. -0.2%; p-int = 0.04). Conclusions The treatment effect of NOAC vs. W is consistent irrespective of APT at baseline for S/SEE, major bleeding, and ACM. Given higher rates of bleeding in AF pts treated with both APT and anticoagulation, concomitant APT should be avoided when possible. In pts requiring concomitant APT, NOAC instead of W should be considered owing to greater absolute safety benefit for ICH, which should be weighed against individual patient-specific risk factors for GI bleeding.