Risk Of Gastrointestinal Bleeding Research Articles

Abstract 15372: Machine Learning Distinguishes Continuous Risk of Gastrointestinal Bleeding, Stroke, and Death in Ambulatory Lvad Patients

Introduction: Advanced data analytics are needed to reliably predict bleeding and thrombotic risk in ambulatory left ventricular assist device (LVAD) patients. Hypothesis: Machine learning techniques can be used to predict risk of gastrointestinal bleeding (GIB), stroke, or death in ambulatory LVAD patients. Methods: HeartMate 3 TM LVAD recipients from the MOMENTUM 3 studies with up to 2-year follow-up were included. A multistate model was developed with 5-fold cross-validation to characterize the continuous probability of events after discharge. Model features included pre-implant, index implant, and short- and long-term post-implant clinical features. 85% of patients were used for model derivation and 15% for validation. Model performance was assessed with area under the curve (AUC). With the model features, a risk stratification tool was created by dividing patients’ into terciles of predicted risk. Results: Among 2,056 LVAD patients who survived to hospital discharge, the median age was 59.4 yrs (20.4% Female, 28.6% Black). At 2-years, the incidence of GIB, Stroke, and Death was 25.6%, 6.0% and 12.3%, respectively. Unique models including pre-implant, implant and post-implant features were created for GIB (Figure A), Stroke and Death. In ambulatory LVAD patients, the model could predict 30-day risk of GIB at any time post-implant which was 26.9%, 2.6% and 0.8% in high, medium and low-risk patients respectively (Figure B). Similar risk prediction was performed for stroke and death. The cross-validated AUC in the derivation cohort was 0.70, 0.69, and 0.85 for GIB, stroke, and death respectively. Conclusion: We developed an innovative risk tool informed by machine learning techniques that predicts risk of GIB, stroke, and death at any 30-day interval in ambulatory LVAD patients with readily available clinical data. The model allows for risk stratification that accurately predicts future events and may be useful to guide clinical decision making.

Abstract 12967: Early Gastrointestinal Bleeding is Most Common Hemorrhagic Complication After Watchman Implantation

Introduction: Left atrial appendage occlusion (LAAO) with the Watchman device is increasingly used for patients with an indication for anticoagulation for atrial fibrillation (AF) and a contraindication to long term anticoagulation. Real world early outcomes in this high-risk patient population are scarce. Methods: We retrospectively evaluated a healthcare system registry of 1200 patients who underwent LAAO with Watchman 2.5 or FLX between 10/2018 and 8/2021 and included 849 patients with 6-month follow-up. We classified complications in 3 distinct categories (immediate procedural, 6-week post-procedural and 6-month post-procedural) and tracked all thromboembolism, hemorrhage and mortality that occurred after the immediate procedural complications. Results: Mean age was 77.6 ± 8.3 years old, 49% were female, 68% had paroxysmal AF, mean CHA 2 DS 2 -VASc was 5.0 ± 1.4, and mean HAS-BLED was 2.9 ± 1.0. Immediate procedural complication rate was 2.4% (access site n=16; tamponade n=2; esophageal injury n=2). 6-week post-procedural complication rate was 4.2% whereas 6-month post-procedural complication rate was 2.0% (% per 100 patient-months). Overall post-procedural complication rate after 6.2 ± 1.1 months was 2.6% of which 0.3% were thromboembolic, 1.2% were hemorrhagic and 1.1% were mortality events (% per 100 patient-months). Gastrointestinal bleeding (GIB) made up 39% and 83% of post-procedural and hemorrhagic complications respectively. Time-indexed post-procedural GIB rate was higher during 6-week period compared to 6-month period (1.9% vs. 0.7%, p=0.00003). Patients with most common indication for LAAO (high risk for bleeding or history of major bleeding, 82.0%) had higher odds of post-procedural GIB than those without bleeding indication (7.0% vs. 2.6%, OR=2.8, p=0.02). GIB was not significantly associated with mortality. Conclusions: Post-LAAO complication rate was low and decreased over time when comparing 6-week and 6-month periods in a high-risk patient population. Early GIB was the most common hemorrhagic complication and patients with bleeding indication for LAAO had a higher risk of GIB within the first 6 months after procedure. Further studies targeting ideal antithrombotic regimen after Watchman implantation are needed.

Safety of early antiplatelet administration in patients with acute ischemic stroke treated with alteplase (SEAPT-24)

ObjectivesAlteplase, a tissue-type plasminogen activator, is recommended for ischemic stroke patients presenting within 4.5 h. Due to bleeding risks, current guidelines advise delaying antiplatelet therapy for 24 h after alteplase. However, specific scenarios may require antiplatelet therapy to be given within the 24 h window. This study aimed to examine the safety of early antiplatelet therapy administration within the first 24 h after alteplase. Materials and methodsThis study is a retrospective, observational study of adult patients with acute ischemic stroke who received alteplase across a multi-hospital system. Patients were grouped based on early antiplatelet therapy (within 24 h window) or as recommended per guidelines. The occurrence of bleeding events, including symptomatic intracranial hemorrhage and/or gastrointestinal bleeding, in-hospital mortality, unfavorable outcomes (modified Rankin score 3–6), and hospital length of stay, were compared between groups. ResultsPatients were predominantly African American (72%) and female (53%) with a median age of 62 years. Median baseline NIHSS scores were higher in the early group (5 vs. 7; p = 0.04), and patients in the early group were more likely to undergo endovascular therapy (26% vs. 8%, p < 0.0001). In patients treated with alteplase only and who did not undergo endovascular therapy, there was no difference in symptomatic intracranial hemorrhage (1.4% vs. 0%, p = 0.1), gastrointestinal bleeding, in-hospital mortality, unfavorable outcomes, or length of stay. ConclusionsIn our retrospective analysis, early administration of antiplatelet therapy (< 24 h post-alteplase) did not increase the risk of symptomatic intracranial hemorrhage, gastrointestinal bleeding, or unfavorable outcomes in patients who received alteplase alone for management of acute ischemic stroke. Prospective studies are needed to validate these findings.

Gastrointestinal bleeding in patients with continuous-flow left ventricular assist devices: A comprehensive review.

Gastrointestinal bleeding is a major cause of morbidity that plagues the quality of life of patients supported on contemporary continuous-flow left ventricular assist devices (CF-LVADs). Despite benefits in survival and the nearly 50% reduction in complications provided by CF-LVADs, bleeding remains one of the most frequent adverse events with CF-LVAD implants. The CF-LVADs cause an increased risk of bleeding mainly due to the activation of the coagulation cascade. A literature search was done using PubMed and Google Scholar from Inception to February 2022. Qualitative analyses of the articles retrieved were used to construct this review. This review attempts to provide a comprehensive summary of the epidemiology, pathophysiology, risk stratification, and management of gastrointestinal bleeding as a complication of CF-LVAD as well as propose an algorithm for diagnosis and treatment. Bleeding can occur at different sites in the gastrointestinal tract, the most common underlying pathology being arteriovenous malformations located in the upper gastrointestinal tract The increased prevalence of gastrointestinal (GI) bleeding in CF-LVAD patients has been attributed to the physiology of the LVAD itself, the use of anticoagulants, as well as patient comorbidities. Management involves pharmacologic and nonpharmacologic strategies. CF-LVAD-supported patients have a significant risk of GI bleeding that is mainly caused by arteriovenous malformations located in the upper GI tract. The increased prevalence of GI bleeding in CF-LVAD patients is attributed to several etiologies that include factors attributed to the device itself and extrinsic factors such as the use of anticoagulation.

Comparative Effectiveness and Safety Between Apixaban, Dabigatran, Edoxaban, and Rivaroxaban Among Patients With Atrial Fibrillation : A Multinational Population-Based Cohort Study.

Current guidelines recommend using direct oral anticoagulants (DOACs) over warfarin in patients with atrial fibrillation (AF), but head-to-head trial data do not exist to guide the choice of DOAC. To do a large-scale comparison between all DOACs (apixaban, dabigatran, edoxaban, and rivaroxaban) in routine clinical practice. Multinational population-based cohort study. Five standardized electronic health care databases, which covered 221 million people in France, Germany, the United Kingdom, and the United States. Patients who were newly diagnosed with AF from 2010 through 2019 and received a new DOAC prescription. Database-specific hazard ratios (HRs) of ischemic stroke or systemic embolism, intracranial hemorrhage (ICH), gastrointestinal bleeding (GIB), and all-cause mortality between DOACs were estimated using a Cox regression model stratified by propensity score and pooled using a random-effects model. A total of 527226 new DOAC users met the inclusion criteria (apixaban, n = 281320; dabigatran, n = 61008; edoxaban, n = 12722; and rivaroxaban, n = 172176). Apixaban use was associated with lower risk for GIB than use of dabigatran (HR, 0.81 [95% CI, 0.70 to 0.94]), edoxaban (HR, 0.77 [CI, 0.66 to 0.91]), or rivaroxaban (HR, 0.72 [CI, 0.66 to 0.79]). No substantial differences were observed for other outcomes or DOAC-DOAC comparisons. The results were consistent for patients aged 80 years or older. Consistent associations between lower GIB risk and apixaban versus rivaroxaban were observed among patients receiving the standard dose (HR, 0.72 [CI, 0.64 to 0.82]), those receiving a reduced dose (HR, 0.68 [CI, 0.61 to 0.77]), and those with chronic kidney disease (HR, 0.68 [CI, 0.59 to 0.77]). Residual confounding is possible. Among patients with AF, apixaban use was associated with lower risk for GIB and similar rates of ischemic stroke or systemic embolism, ICH, and all-cause mortality compared with dabigatran, edoxaban, and rivaroxaban. This finding was consistent for patients aged 80 years or older and those with chronic kidney disease, who are often underrepresented in clinical trials. None.

항응고제/항혈소판제와 프로톤펌프억제제 병용의 경제성 평가에 대한 체계적 문헌고찰

Anticoagulants/antiplatelets are effective in preventing cardiovascular diseases (CVDs). However, as an adverse effect, the risk of upper gastrointestinal bleeding (UGIB) leads to additional costs due to increased treatment and decreased quality of life. Accordingly, the administration of proton pump inhibitors (PPI) is recommended to prevent UGIB. We conducted a systematic review of economic evaluations of PPI co-therapy for patients taking long-term anticoagulants/ antiplatelets to prevent CVDs to examine the cost effectiveness of PPI co-therapy. We searched literature from PubMed and EMBASE with keywords including types of economic evaluations and active ingredients of anticoagulants and antiplatelets on 13/07/2022. Two independent reviewers conducted a systematic review. As a result, six economic evaluation studies were identified. All studies compared PPI co-therapy with low-dose aspirin to prevent CVDs. We confirmed the cost-effectiveness of PPI co-therapy with the respective incremental cost-effectiveness ratio (ICER) in each base case. In the sensitivity analyses, the PPI cost and adherence influenced the ICER the most. The quality of reporting, which was assessed using the Consolidated Health Economic Evaluation Reporting Standards checklist, was 87-96%. In the present study, we found that PPI co-therapy was cost-effective and tended to improve the patient’s life years and quality-adjusted life years. These results can be used as evidence for further economic evaluation studies to verify the costeffectiveness of anticoagulants/antiplatelets and PPI co-therapy.

Incidence of Gastrointestinal Bleeding After Transesophageal Echocardiography Use in Orthotopic Liver Transplantation.

The risk of upper gastrointestinal bleeding (UGIB) after transesophageal echocardiography (TEE) in patients with high grade esophageal varices (EV) that are undergoing Orthotopic Liver transplantation (OLT) is poorly understood. This was a retrospective single-centre cohort study in all patients that underwent OLT at Queen Elizabeth Hospital Birmingham between September 2016 and September 2018. The primary outcome was to determine the incidence of UGIB in patients that have undergone OLT with EV that received TEE. 401 patients were included in the study, of which 320 (80%) received TEE. The incidence of post-operative UGIB in patients that received TEE was 1.6% (5/320) in the entire cohort: 2.7% (4/149) in patients with no evidence of EV and 0.6% (1/171) in patients with EV. UGIB occurred in 1 patient with grade 2 EV and did not occur in patients with grade 1 or 3 EV. The incidence of UGIB in patients that received TEE was not statistically different to patients that did not: 1.6% (5/320) vs. 3.7% (3/81) p = 0.218. In conclusion, in patients that underwent OLT, intra-operative TEE use was associated with low rates of UGIB, even in cohorts with high grade EV. This suggests that TEE is a relatively safe method of haemodynamic monitoring in patients undergoing OLT.

Gastrointestinal Bleeding on Oral Anticoagulation: What is Currently Known.

Gastrointestinal bleeding (GIB) is the most common type of bleeding occurring in patients on oral anticoagulation. A meta-analysis of the landmark randomized controlled trials (RCTs) for patients with atrial fibrillation demonstrated that direct oral anticoagulants (DOACs) were associated with higher GIB rates compared to warfarin. However, significant heterogeneity existed between studies. While rivaroxaban, high-dose dabigatran, and high-dose edoxaban were associated with higher GIB rates than warfarin, GIB rates were similar between warfarinusers and both apixaban and low-dose dabigatranusers. Additionally, previous observational studies have yielded conflicting reports on whether GIB rates differ between warfarin and DOACs. Meta-analyses of observational studies demonstrated that warfarin is associated with lower rates of GIB compared to rivaroxaban, similar or lower rates compared to dabigatran, and higher rates compared to apixaban. Importantly, no RCT has compared individualDOACs directly and due to the different selection criteria of the initial RCTs, indirect comparisons between DOACs using these studies are unreliable. The best available information of comparisons between individual DOACs is therefore limited to observational studies. There is mounting evidence that suggests that rivaroxaban is associated with a higher risk of GIB compared to other DOACs. Finally, GIB induced by oral anticoagulation may have some positive aspects. Interestingly, there are studies that indicate oral anticoagulation facilitates colorectal cancer detection. Furthermore, results from RCTs and observational studies suggest that warfarin may even decrease the incidence of cancer.

Post-Implant Phosphodiesterase-5 Inhibitors in Patients with Left Ventricular Assist Device: A Systematic Review and Meta-Analysis.

Background: Despite the improvement in left ventricular assist device (LVAD) technology and the advent of third-generation LVADs, hemocompatibility-related events remain a significant issue. Therefore, new pharmacological treatments are necessary to optimize patient management and to further reduce hemocompatibility-related events. The purpose of the present systematic review and meta-analysis was to summarize the existing data regarding the safety and efficacy of post-implant phosphodiesterase-5 inhibitors (PDE-5i) on hemocompatibility-related events. Methods: Among the 258 articles in Pubmed, Scopus, and CENTRAL that were retrieved (1990–2022), 15 studies were included in the qualitative synthesis, and 9 studies were included in the quantitative synthesis. The fixed-effects model was used because it is statistically sound for combining a very small number of studies. The primary endpoint of the study was all-cause mortality, whereas the secondary endpoints were ischemic stroke, pump thrombosis, and gastrointestinal bleeding. Results: Mortality was significantly lower in the PDE-5i group vs. the control group (OR: 0.92 [95% CI: 0.85, 0.98]; p = 0.02). The secondary endpoints ischemic stroke (OR: 0.87 [95% CI: 0.78, 0.98]; p = 0.02) and pump thrombosis (OR: 0.90 [95% CI: 0.82, 0.99]; p = 0.04) were also lower in the PDE-5i group. The incidence of gastrointestinal bleeding was significantly higher in patients with LVAD receiving PDE-5i (OR: 1.26 [95% CI: 1.11, 1.44]; p < 0.01). In the overall analysis, the heterogeneity of outcomes was low, except for pump thrombosis. Conclusions: The use of PDE-5i post-implant was associated with lower mortality and thrombotic events but with a higher risk of gastrointestinal bleeding.

Red blood cell distribution width predicts gastrointestinal bleeding after coronary artery bypass grafting

BackgroundRed blood cell distribution width (RDW) is highly associated with adverse clinical outcomes in many diseases. The present study aimed to evaluate the relationship between RDW and gastrointestinal bleeding (GIB) after isolated coronary artery bypass grafting (CABG).MethodsThis was a retrospective observational study that included 4473 patients who received CABG, and all the data were extracted from the Medical Information Mart for Intensive Care III database. Data collected included patient demographics, associated comorbid illnesses, laboratory parameters, and medications. The receiver operating characteristic (ROC) curve was used to determine the best cutoff value of RDW for the diagnosis of GIB. Multivariable logistic regression analysis was used to analyze the relationship between RDW and GIB.ResultsThe incidence of GIB in patients receiving CABG was 1.1%. Quartile analyses showed a significant increase in GIB incidence at the fourth RDW quartile (> 14.3%; P < 0.001). The ROC curve analysis revealed that an RDW level > 14.1% measured on admission had 59.6% sensitivity and 69.4% specificity in predicting GIB after CABG. After adjustment for confounders, high RDW was still associated with an increased risk of GIB in patients with CABG (odds ratio = 2.83, 95% confidence interval 1.46–5.51, P = 0.002).ConclusionsOur study indicates that the elevated RDW level is associated with an increased risk of GIB after CABG, and it can be an independent predictor of GIB. The introduction of RDW to study GIB enriches the diagnosis method of GIB and ensures the rapid and accurate diagnosis of GIB.

Biases in reporting of adverse effects in clinical trials, and potential impact on safety assessments in systematic reviews and therapy guidelines.

Clinical trials are an important source of adverse effects data, including analyses in systematic reviews and recommendations in therapy guidelines. Trial publication bias may have profound effects on safety perceptions. This MiniReview presents and discusses biases in reporting of safety data in clinical trials and the implications for systematic reviews and guidelines. The objectives of this work are to analyse risk of gastrointestinal bleeding in systemic corticosteroid trials and to assess adverse effects reporting in a fluoxetine trial in depression (Treatment for Adolescents With Depression Study [TADS]) and descriptions of adverse effects in adolescent depression therapy guidelines. We performed literature reviews and descriptive analyse of clinical trials with corticosteroids, and publications from the TADS trial. Risk of gastrointestinal bleeding from corticosteroids was analysed by meta-analysis. Gastrointestinal bleeding definitions varied considerably between trials. The incidence was significantly increased in hospitalized, but not in ambulant, patients compared to placebo. We identified several biases concerning TADS safety reporting, including severity thresholds and nonpublication of most adverse effects data beyond the initial 12 weeks. Therapy guidelines on adolescent depression mentioned suicidality risk, but many failed to mention other adverse effects. We identified several pitfalls in adverse effects reporting in clinical trials. These include heterogeneous disease definitions, reporting thresholds, and incomplete reporting. Trial bias may have great impact on risk assessments in systematic reviews and meta-analyses.

Prevalence of H. pylori among patients undergoing coronary angiography (The HP-DAPT prevalence study)

Helicobacter pylori (H. pylori) screening and treatment is recommended for patients on chronic aspirin (ASA) therapy to reduce the risk of gastrointestinal bleeding. Coronary artery disease patients requiring combination antithrombotic therapy (dual antiplatelet therapy; DAPT, or dual pathway inhibition; DPI) are at an even higher risk of GI bleeding. Therefore, we aimed to evaluate the prevalence of H. pylori among patients referred for angiography and likely to receive DAPT or DPI. This single-center prospective observational study recruited patients undergoing coronary angiography and with the possibility of requiring DAPT or DPI. All included patients underwent H. pylori serology testing. Multivariable logistic regression was performed to determine predictors of seropositivity. 195 patients were included in the analysis. Mean age was 67 years, 50% had known prior CAD, and 49% underwent coronary intervention. H. pylori serology was positive in 36%. Chronic kidney disease (odds ratio [OR] 2.76; 95% confidence interval [CI] 1.24 to 6.15; p = 0.01) and chronic obstructive pulmonary disease (OR 2.52; 95% CI 1.14 to 5.55; p = 0.02) history were independent predictors of H. pylori seropositivity. Given the clinically significant prevalence of H. pylori seropositivity among patients referred for angiography, systematic screening strategies and eradication of H. pylori could significantly reduce the incidence of GI bleeding in patients requiring DAPT or DPI.

Protective effect of proton pump inhibitor against gastrointestinal bleeding in patients receiving oral anticoagulants: a systematic review and meta-analysis

Abstract Background The concurrent use of proton pump inhibitor (PPI) in oral anticoagulant (OAC) treated patients may be associated with a lower risk of gastrointestinal bleeding (GIB), but evidence is still conflicting according to individual OACs. Purpose We conducted a meta-analysis to estimate the risk of GIB in patients with OAC and PPI co-therapy. Methods A systematic search of PubMed, EMBASE, and Cochrane was performed for studies reporting GIB risk in OAC and PPI co-therapy. Primary outcomes were total GIB and major GIB events. We calculated pooled estimates of GIB risk by a random-effect meta-analysis and reported as odds ratios (OR) and 95% CI. Stratified analyses according to the origin of GIB, ethnic groups, individual OACs, and the presence of underlying GIB risk factors were performed. Results A total of 10 studies (1 randomized controlled study and 9 observational studies) and 1,970,931 patients who received OAC were included. OAC and PPI co-therapy were associated with a lower risk of total GIB, and major GIB; OR (95% CI) was 0.67 (0.62–0.74) for total GIB and 0.68 (0.63–0.75) for major GIB, respectively. Among total GIB, only the risk of upper GIB was lower with OAC and PPI co-therapy (OR 0.67, 95% CI 0.64–0.70). No difference in the lower risk of primary GIB outcomes of PPI co-therapy was observed between Asians and non-Asians (p-for-difference, total GIB=0.695, major GIB=0.748, respectively) and among individual OACs except for edoxaban. The protective effect of PPI on total GIB was more significant in high-risk patients, defined as those with concurrent medication of antiplatelets or non-steroidal anti-inflammatory drugs (OR 0.62, 95% CI 0.52–0.73) and presence of high bleeding risk factors such as previous GIB history, HAS-BLED score ≥3, or underlying gastrointestinal diseases. (OR 0.65, 95% CI 0.61–0.70). Conclusion In patients who receive OAC, the use of PPI co-therapy was associated with a lower risk of total GIB and major GIB irrespective of ethnic group and OAC type except for edoxaban. PPI co-therapy can be considered particularly in patients on concomitant NSAID and antiplatelet use or patients with high GIB risk factors. Funding Acknowledgement Type of funding sources: None.

Previous antithrombotic therapy does not have an impact on the in-hospital mortality of patients with upper gastrointestinal bleeding

Abstract Background The association between antithrombotic therapy due to concomitant cardiovascular disorders and the risk of gastrointestinal bleeding is well known; however, data regarding the influence of antithrombotics on outcomes and further management after a bleeding episode are scarce. Purpose This study was conducted to assess the impact of concomitant antithrombotic therapy and other variables on in-hospital and 6-month outcomes and to determine the re-initiation rate of the antithrombotic treatment after a bleeding event. Methods We retrospectively analysed all patients with upper gastrointestinal bleeding (UGB) who underwent urgent gastroscopy in 3 centres from 1 January 2019 to 31 December 2019. Demographic and medical data were collected from the electronic hospital database system. Results Among 333 patients (60% males, mean age 69±16 years), 44% were receiving antithrombotics. The in-hospital mortality rate was 12%, and the 6-months was 32%. In logistic regression we observed no association between antithrombotics and worse in-hospital outcomes. Haemorrhagic shock (OR 5.7, 95% CI 2.7 to 12.2; p&amp;lt;0.001), as well as a history of cancer (OR 2.7, 95% CI 1.1 to 6.9; p=0.03) and higher comorbidity (mean Charlson comorbidity index 5.6 vs. 6.9, OR 1.3, 95% CI 1.1 to 1.6; p=0.005) led to higher in-hospital mortality (tab. 1). In terms of 6-months outcomes, higher age (OR 1.03, 95% CI 1.00 to 1.05; p=0.02), higher comorbidity (OR 1.4, 95% CI 1.2 to 1.6; p&amp;lt;0.001), a history of cancer (OR 4.5, 95% CI 2.0 to 10.1; p&amp;lt;0.001) and a history of liver cirrhosis (OR 2.3, 95% CI 1.2 to 4.6; p=0.02) were associated with higher mortality. Other tested variables such as ischemic heart disease, heart failure or diabetes did not influence 6-month outcomes at statistically significant level (tab. 2). After a bleeding episode, antithrombotic treatment in patients with lasting indication from cardiovascular reasons was re-initiated in 81% of cases. One patient with atrial fibrillation was referred for a left atrial appendage closure. Conclusions Based on our observations, previous antithrombotic therapy does not worsen in-hospital outcomes in patients with UGB. Development of haemorrhagic shock during hospitalization predicted poor prognosis. Higher 6-month mortality was observed in older patients and patients with a history of liver cirrhosis. A history of cancer and higher comorbidity negatively affected the short- as well as long-term prognosis. Funding Acknowledgement Type of funding sources: None.

Antiplatelet therapy and risk of adverse cardiovascular events in peripheral artery disease

Abstract Background Antiplatelet therapy has been shown to reduce adverse cardiovascular (CV) events in patients with PAD, but despite the well-established medication benefit, large-scale epidemiological data evaluating antiplatelet agent of choice with low bleeding risk and high antithrombotic effect is sparse. Purpose We explored Danish healthcare registers to examine guideline-recommended antiplatelet therapy and associated risk of adverse CV outcomes in patients with PAD. Methods All patients with a first-time diagnosis of PAD between January 1, 1997 and December 31, 2016 were identified. Patients alive six months after diagnosis were divided into four treatment groups: aspirin, clopidogrel, dual therapy (DAPT), and no antiplatelet therapy. Logistic regression models were used to estimate 1-year risk of myocardial infarction (MI), stroke, CV death, all-cause mortality, and gastrointestinal (GI) bleeding. Results We identified a total of 85,771 PAD patients [median age 70.6 (IQR 63–77 years), 52% male]. The results suggest that compared to no antiplatelet therapy, use of clopidogrel alone significantly decreased 1-year risk of incident MI, stroke, CV death and all-cause mortality with odds ratios 0.56 (CI 0.46–0.68), 0.69 (CI 0.59–0.81), 0.72 (CI 0.56–0.94), and 0.79 (CI 0.65–0.97) respectively. Likewise, aspirin monotherapy was associated with only a marginal reduction in 1-year risk of stroke by 11% and all-cause mortality by 7%. Odds ratios for GI bleeding were estimated to be 1.18 (CI 1.04–1.34), 1.34 (CI 0.94–1.91), and 1.54 (CI 1.05–2.26) for aspirin, clopidogrel, and DAPT groups, respectively. Conclusion In this nationwide study, clopidogrel is associated with significantly reduced risk of MI, stroke, CV death and all-cause mortality with low risk of bleeding and appears to support clopidogrel as antiplatelet agent of choice for CV risk reduction in patients with PAD. Funding Acknowledgement Type of funding sources: None.

Association between postoperative hemodynamic metrics of pulmonary hypertension and right ventricular dysfunction and clinical outcomes after left ventricular assist device implantation.

While preoperative hemodynamic risk factors associated with early right heart failure (RHF) following left ventricular assist device (LVAD) surgery are well-established, the relationship between postoperative hemodynamic status and subsequent outcomes remains poorly defined. We analyzed adult CF-LVAD patients from the STS-INTERMACS registry surviving at least 3 months without evidence of early RHF and with hemodynamic data available at 3 months after LVAD implant. The association between metrics of RV afterload and function and the subsequent risk of death, right heart failure (RHF), gastrointestinal bleeding (GIB), or stroke were assessed using multivariable Cox proportional hazards modeling. Among 1,050 patients with available 3-month hemodynamics, pulmonary hypertension was common, with 585 (55.7%) having mPAP ≥ 20 mm Hg and 164 (15.6%) having PVR ≥ 3 WU. Pulmonary artery pulsatility index (PAPi, HR 0.62 per log-increase for values < 3, 95% CI 0.43-0.89) and PVR (HR 1.19 per 1 WU-increase for values > 1.5 WU, 95% CI 1.03-1.38) were independently associated with the composite of death or RHF. Postoperative RAP (HR 1.18 per 5 mm Hg increase, 95% CI 1.04-1.33), RAP:PCWP (HR 1.46 per log-increase, 95% CI 1.12-1.91), and PAPi (HR 0.76 per log-increase, 95% CI 0.61-0.95) were each associated with GIB risk. Postoperative hemodynamics was not associated with stroke risk. Hemodynamic metrics of postoperative RV dysfunction and elevated RV afterload are independently associated with RHF, mortality and GIB. Whether strategies targeting postoperative optimization of RV function and afterload can reduce the burden of these adverse events requires prospective study.

S677 Overt Gastrointestinal Bleeding in Patients With Cancer: Clinical Characteristics and Outcomes

S677 Overt Gastrointestinal Bleeding in Patients With Cancer: Clinical Characteristics and Outcomes

S1563 ACE Inhibitor Use Is Associated With Angioectasias on Video Capsule Endoscopy (VCE) in Patients With Iron Deficiency Anemia

Introduction: Small bowel bleeding poses a clinical challenge in patients with vascular lesions. Bleeding recurrence after endoscopic therapy is high and medical therapies have limited efficacy. In those with left ventricular assist devices (LVADs), the use of angiotensin converting enzyme inhibitors (ACEi) has been associated with a reduced rate of gastrointestinal bleeding. Conversely, the antiplatelet effects of ACEi have been described thought due to their effects in decreasing platelet aggregation. Our aim was to determine whether ACEi or angiotensin receptor blocker (ARB) therapy had an impact on the rate of positive VCE small bowel findings in those with iron deficiency anemia (IDA). Methods: Data was collected from consecutive inpatient and outpatient VCE examinations performed between January 1, 2009 to March 1, 2018 at a single U.S. tertiary medical center performed for IDA. VCE studies were excluded in those with incomplete small bowel examinations (9) or technical failure (1). Patient demographics, laboratory values, medication use and endoscopic findings were recorded. VCE findings were based on the P0-P2 grading system. The primary outcome of interest was a positive (P2) VCE. Data were analyzed using Wilcoxon rank-sum test for continuous variables and Fischer’s exact test for dichotomous variables. Bivariate logistic regression was performed to identify independent factors predictive of positive VCE. Results: Eighty-two VCE were included in the final analysis. Median age was 67.6 (IQR: 57.1-75.5) years and 38 (46.3%) patients were male. Thirty-seven (45.1%) VCE examinations were positive with the most common finding of angiectasia in 21 (55.3%). Risk factors for positive VCE are listed in Table 1. In univariate analysis, ACEi therapy associated with both positive VCE (P=0.014) and the presence of angiectasia (P=0.021), whereas ARB therapy did not associate with positive VCE. ACEi findings remained significant in bivariate analysis after controlling for cardiac and pulmonary comorbidities. Conclusion: In this single center study the presence of ACEi use was associated with small bowel and/or stomach angiectasias on VCE in univariate analysis and when controlled for cardiac and pulmonary risk factors. Further studies are required to determine the mechanistic impact of ACEi on gastrointestinal bleeding risk such as the reduction in von Willebrand factor or factors that affect platelet aggregation. Table 1. - Univariate predictors of positive video capsule endoscopy in iron deficiency anemia Negative VCE (n = 45) Positive VCE (n =37) P-value Age, years, mean (SD) 63.6 (15.8) 68.6 (9.3) 0.303 Male sex, n (%) 21 (46.7) 17 (46) 1 White race, n (%) 22 (48.9) 20 (54.1) 0.223 Active smoking, n (%) 6 (14) 11 (29.7) 0.105 Outpatient location, n (%) 31 (68.9) 21 (56.8) 0.357 Chronic kidney disease, n (%) 10 (22.2) 13 (35.1) 0.224 Chronic liver disease, n (%) 3 (6.7) 4 (10.8) 0.696 Congestive heart failure, n (%) 10 (22.2) 13 (35.1) 0.224 Diabetes mellitus, n (%) 15 (33.3) 15 (40.5) 0.645 Cardiac valvular disease, n (%) 7 (15.6) 6 (16.2) 1 Coronary artery disease, n (%) 14 (31.1) 14 (37.8) 0.641 Cardiac arrhythmia, n (%) 10 (22.2) 18 (48.7) 0.019 Chronic lung disease, n (%) 10 (22.2) 13 (35.1) 0.224 Left ventricular assist device, n (%) 2 (4.4) 2 (5.4) 1 Blood transfusion in the preceding 4 weeks, n (%) 17 (37.8) 16 (43.2) 0.656 Aspirin, n (%) 20 (44.4) 14 (37.8) 0.654 Thienopyridine, n (%) 3 (6.7) 2 (5.4) 1 Coumadin, n (%) 1 (2.2) 5 (13.5) 0.086 SSRI/SNRI, n (%) 7 (15.6) 9 (24.3) 0.404 ACEi 7 (15.6) 15 (40.5) 0.014 ARB 9 (20) 7 (18.9) 1 Hemoglobin, g/dL1 9.9 (1.7) 9.2 (2.3) 0.216 Platelets, 109/L1 225.4 (67.5) 208.6 (84.9) 0.202 BUN, mg/dL1 21.9 (13.1) 26.7 (22) 0.869 Creatinine, mg/dL1 1.3 (0.5) 1.9 (1.5) 0.197 Ferritin, ng/mL,1 128 (259) 39.6 (28.7) 0.966 Percent saturation, %1 14.8 (15.1) 13.7 (15.4) 0.76

EMERGING DATA FOR CANCER ASSOCIATED THROMBOSIS TREATMENT

Venous thromboembolism (VTE) is a common complication in patients with malignancies,resulting in deep vein thrombosis, pulmonary embolism and central venous catheter VTE, and is responsible for high morbidity and mortality (1). The prevalence of cancer-associated thrombosis is increasing because of multiple factors, including longer patient survival, anticancer therapies, increased detection of incidental VTE during surveillance imaging, and wider use of central venous catheters. Anticoagulant therapy with low-molecular-weight heparins (LMWHs) was the standard of care for the treatment of cancer-associated thrombosis, with vitamin K antagonists providing a secondary treatment option, until direct oral anticoagulants (DOAC) emerged as alternative first-line treatment options in 2016 (2). Rivaroxaban, Edoxaban and Apixaban are recommended as initial treatment in patients with cancer-associated thrombosis who are not at high risk of gastrointestinal or genitourinary bleeding (3). LMWHs and Fondaparinux are still recommended for prophylaxis of VTE in medically-treated patients with cancer. Rivaroxaban and Apixaban can be used selectively for thromboprophylaxis in patients with malignancies at high risk of VTE, for example in patients with pancreatic cancer or myeloma (4,5). Anticoagulant choice should incorporate a personalised medicine approach that considers cancer type, VTE and bleeding risk factors, drug–drug interactions (DDI), and patient preferences. Patients with cancer often experience narrow therapeutic index polypharmacy and undergo treatment for several simultaneous comorbidities. In this setting the risk of DDI is high in particular during therapy with tyrosine kinase inhibitors (6). Concerns on DDI management include decreased efficacy and bleeding risk. In general, DOAC use is not advisable in combination with drugs that are strong inhibitors of both P-gp and/or CYP3A4 for high bleeding risk and in combination with strong inducers of Pgp and/or CYP3A4 that could markedly reduce DOAC plasma levels. Routine use of plasma level measurements for DOAC, only available in few laboratory centres, is not currently recommended (7). Nevertheless it has recently become increasingly clear that clinicians need to assess the anticoagulant status of a patient receiving anticancer therapies. The global coagulation Test of thrombin generation (TGT) a sensitive method to assess the anticoagulant therapy, provides a global measure of anticoagulant effect by measuring the inhibition of formation of thrombin (FIIa), a common endpoint for both LMWH and FXa inhibitors (8). Furthers studies are warranted to better define the future role of this coagulation test in this subgroup of patients.

Prophylactic acid suppressants in patients with primary neurologic injury: A systematic review and meta-analysis of randomized controlled trials.

Neurocritical care patients are at risk of stress-induced gastrointestinal ulceration. We performed a systematic review and meta-analysis of stress ulcer prophylaxis (SUP) in critically ill adults admitted with a primary neurologic injury. We included randomized controlled trials (RCTs) comparing SUP with histamine-2-receptor antagonists (H2RAs) or proton pump inhibitors (PPIs) to placebo/no prophylaxis, as well as to each other. The primary outcome was in-ICU gastrointestinal bleeding (GIB). Predefined secondary outcomes were all-cause 30-day mortality, ICU length of stay (LOS), nosocomial pneumonia, and other complications. We identified 14 relevant trials enrolling 1036 neurocritical care patients; 11 trials enrolling 930 patients were included in the meta-analysis. H2RAs resulted in a lower incidence of GIB as compared to placebo or no prophylaxis (Risk ratio [RR] 0.42, 95% CI 0.30-0.58; p < 0.001); PPIs with a lower risk of GIB compared to placebo/no prophylaxis (RR 0.37, 95% CI 0.23-0.59; p < 0.001). No significant difference was observed in GIB comparing PPIs with H2RAs (RR 0.53, 95% CI 0.26-1.06; p = 0.07; I2 = 0%). In neurocritical care patients, the overall high or unclear risk of bias of individual trials, the low event rates, and modest sample sizes preclude strong clinical inferences about the utility of SUP.