Evaluation and treatment of gastrointestinal bleeding in patients taking anticoagulants presenting to the emergency department.

This manuscript is a consensus document of an expert panel on the Evaluation and Treatment of Gastrointestinal Bleeding in Patients Taking Anticoagulants Presenting to the Emergency Department, sponsored by the American College of Emergency Physicians.

Management of Anticoagulant and Antiplatelet Agents in Acute Gastrointestinal Bleeding and Prevention of Gastrointestinal Bleeding.

Managing gastrointestinal bleeding in patients using antithrombotic agents remains challenging in clinical practice. This review article provides a comprehensive and evidence-based approach to managing acute antithrombotic-related gastrointestinal bleeding, focusing on the triage of patients, appropriate resuscitation, and timely endoscopy. The latest clinical practice guidelines are highlighted to guide decisions concerning the use of reversal agents, temporary interruption, and resumption of antithrombotic drugs. Additionally, preventive measures are discussed to lower the risk of future bleeding and minimize complications among patients prescribed antithrombotic drugs.

Contemporary trends and barriers to oral anticoagulation therapy in Non-valvular atrial fibrillation during DOAC predominant era.

There is a need to reassess contemporary oral anticoagulation (OAC) trends and barriers against guideline directed therapy in the United States. Most previous studies were performed before major guideline changes recommended direct oral anticoagulant (DOAC) use over warfarin or have otherwise lacked patient level data. Data on overuse of OAC in low-risk group is also limited. To address these knowledge gaps, we performed a nationwide analysis to analyze current trends. This is a retrospective cohort study assessing non-valvular AF identified using a large United States de-identified administrative claims database, including commercial and Medicare Advantage enrollees. Prescription fills were assessed within a 90-day follow-up from the patient's index AF encounter between January 1, 2016, and December 31, 2020. Among the 339,197 AF patients, 4.4%, 8.0%, and 87.6% were in the low-, moderate-, and high-risk groups (according to CHA2DS2-VASc score). An over (29.6%) and under (52.2%) utilization of OAC was reported in low- and high-risk AF patients. A considerably high frequency for warfarin use was also noted among high-risk group patients taking OAC (33.1%). The results suggest that anticoagulation use for stroke prevention in the United States is still comparable to the pre-DOAC era studies. About half of newly diagnosed high-risk non-valvular AF patients remain unprotected against stroke risk. Several predictors of OAC and DOAC use were also identified. Our findings may identify a population at risk of complications due to under- or over-treatment and highlight the need for future quality improvement efforts.

Periprocedural Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant Undergoing a Digestive Endoscopy.

INTRODUCTION: The periprocedural management of patients with atrial fibrillation (AF) using a direct oral anticoagulant (DOAC) undergoing elective gastrointestinal (GI) endoscopic procedure remains uncertain. We investigated the safety of a standardized periprocedural DOAC management strategy. METHODS: The Periprocedural Anticoagulation Use for Surgery Evaluation cohort study enrolled adult patients receiving a DOAC (apixaban, rivaroxaban, or dabigatran) for AF scheduled for an elective procedure or surgery. This analysis addresses patients undergoing digestive endoscopy. Standardized periprocedural management consisted of DOAC interruption 1 day preendoscopy with resumption 1 day after procedure at low-moderate risk of bleeding or 2 days in case of a high bleeding risk. Thirty-day outcomes included GI bleeding, thromboembolic events, and mortality. RESULTS: Of 556 patients on a DOAC (mean [SD] age of 72.5 [8.6] years; 37.4% female; mean CHADS 2 score 1.7 [1.0]), 8.6% were also on American Society of Anesthesiology (ASA) and 0.7% on clopidogrel. Most of the patients underwent colonoscopies (63.3%) or gastroscopies (14.0%), with 18.9% having both on the same procedural day. The mean total duration of DOAC interruption was 3.9 ± 1.6 days. Four patients experienced an arterial thromboembolic event (0.7%, 0.3%-1.8%) within 24.2 ± 5.9 days of DOAC interruption. GI bleeding events occurred in 2.5% (1.4%-4.2%) within 11.1 ± 8.1 days (range: 0.6; 25.5 days) of endoscopy, with major GI bleeding in 0.9% (0.4%-2.1%). Three patients died (0.5%; 0.2%-1.6%) 15.6-22.3 days after the endoscopy. DISCUSSION: After a contemporary standardized periprocedural management strategy, patients with AF undergoing DOAC therapy interruption for elective digestive endoscopy experienced low rates of arterial thromboembolism and major bleeding.

Percutaneous Left Atrial Appendage Occlusion in Comparison to Non-Vitamin K Antagonist Oral Anticoagulant Among Patients With Atrial Fibrillation.

Background This study aimed to compare percutaneous left atrial appendage occlusion (LAAO) with non-vitamin K antagonist oral anticoagulants among patients with atrial fibrillation. Methods and Results Using a US administrative database, 562 850 patients with atrial fibrillation were identified, among whom 8397 were treated with LAAO and 554 453 were treated with non-vitamin K antagonist oral anticoagulants between March 13, 2015 and December 31, 2018. Propensity score overlap weighting was used to balance baseline characteristics. The primary outcome was a composite end point of ischemic stroke or systemic embolism, major bleeding, and all-cause mortality. The mean age was 76.4±7.6 years; 280 097 (49.8%) were female. Mean follow-up was 1.5±1.0 years. LAAO was associated with no significant difference in the risk of the primary composite end point (hazard ratio [HR], 0.93 [0.84-1.03]), or the secondary outcomes including ischemic stroke/systemic embolism (HR, 1.07 [0.81-1.41]), and intracranial bleeding (HR, 1.08 [0.72-1.61]). LAAO was associated with a higher risk of major bleeding (HR, 1.22 [1.05-1.42], P=0.01) and a lower risk of mortality (HR, 0.73 [0.64-0.84], P<0.001). The lower risk of mortality associated with LAAO was most pronounced in patients with a prior history of intracranial bleeding. Conclusions In comparison to non-vitamin K antagonist oral anticoagulants, LAAO was associated with no significant difference in the risk of the composite outcome and a lower risk of mortality, which suggests LAAO might be a reasonable option in select patients with atrial fibrillation. The observation of higher bleeding risk associated with LAAO highlights the need to optimize postprocedural antithrombotic regimens as well as systematic efforts to assess and address bleeding predispositions.

Device-related thrombus following left atrial appendage occlusion.

Thrombus formation on intracardiac devices remains a subject of importance, with rates in the 2-5% range. Device-related thrombus (DRT) following left atrial appendage occlusion is an area of particular concern considering its association with embolic events. DRT continues to present numerous questions, including the optimal definition, incidence, risk factors, monitoring, therapy, and clinical outcomes - all subjects of ongoing assessment. Herein, we discuss these considerations, building upon the relevant historical context and pathophysiologic insights while discussing the future considerations in this rapidly evolving field.

Management of Antiplatelet and Anticoagulant Agents before and after Polypectomy.

Antithrombotic medications, including antiplatelet drugs and anticoagulants, are widely prescribed to prevent thromboembolic disease. There is limited evidence informing gastroenterologists of the management of patients on antithrombotic medications undergoing colonoscopy and polypectomy. A patient's risk of thromboembolism versus postpolypectomy bleeding should be carefully considered, incorporating patient preferences concerning benefits and harms of temporary antithrombotic interruption. We will review the available consensus guidelines, current literature, and strategies to mitigate the risk of bleeding following polypectomy. These will be interpreted in the framework of shared decision-making with the patient to arrive at the safest solution best aligned with the patient's preferences.

American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline: Management of Anticoagulants and Antiplatelets During Acute Gastrointestinal Bleeding and the Periendoscopic Period.

We conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1-7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y12 receptor inhibitor for patients on a single P2Y12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1-7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y12 receptor inhibitor drugs because of insufficient evidence.

American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline: Management of Anticoagulants and Antiplatelets During Acute Gastrointestinal Bleeding and the Periendoscopic Period.

We conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1-7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y12 receptor inhibitor for patients on a single P2Y12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1-7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y12 receptor inhibitor drugs because of insufficient evidence.

Comparative Effectiveness of Machine Learning Approaches for Predicting Gastrointestinal Bleeds in Patients Receiving Antithrombotic Treatment.

Importance: Anticipating the risk of gastrointestinal bleeding (GIB) when initiating antithrombotic treatment (oral antiplatelets or anticoagulants) is limited by existing risk prediction models. Machine learning algorithms may result in superior predictive models to aid in clinical decision-making. Objective: To compare the performance of 3 machine learning approaches with the commonly used HAS-BLED (hypertension, abnormal kidney and liver function, stroke, bleeding, labile international normalized ratio, older age, and drug or alcohol use) risk score in predicting antithrombotic-related GIB. Design, Setting, and Participants: This retrospective cross-sectional study used data from the OptumLabs Data Warehouse, which contains medical and pharmacy claims on privately insured patients and Medicare Advantage enrollees in the US. The study cohort included patients 18 years or older with a history of atrial fibrillation, ischemic heart disease, or venous thromboembolism who were prescribed oral anticoagulant and/or thienopyridine antiplatelet agents between January 1, 2016, and December 31, 2019. Exposures: A cohort of patients prescribed oral anticoagulant and thienopyridine antiplatelet agents was divided into development and validation cohorts based on date of index prescription. The development cohort was used to train 3 machine learning models to predict GIB at 6 and 12 months: regularized Cox proportional hazards regression (RegCox), random survival forests (RSF), and extreme gradient boosting (XGBoost). Main Outcomes and Measures: The performance of the models for predicting GIB in the validation cohort, evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value, and prediction density plots. Relative importance scores were used to identify the variables that were most influential in the top-performing machine learning model. Results: In the entire study cohort of 306 463 patients, 166 177 (54.2%) were male, 193 648 (63.2%) were White, the mean (SD) age was 69.0 (12.6) years, and 12 322 (4.0%) had experienced a GIB. In the validation data set, the HAS-BLED model had an AUC of 0.60 for predicting GIB at 6 months and 0.59 at 12 months. The RegCox model performed the best in the validation set, with an AUC of 0.67 at 6 months and 0.66 at 12 months. XGBoost was similar, with AUCs of 0.67 at 6 months and 0.66 at 12 months, whereas for RSF, AUCs were 0.62 at 6 months and 0.60 at 12 months. The variables with the highest importance scores in the RegCox model were prior GI bleed (importance score, 0.72); atrial fibrillation, ischemic heart disease, and venous thromboembolism combined (importance score, 0.38); and use of gastroprotective agents (importance score, 0.32). Conclusions and Relevance: In this cross-sectional study, the machine learning models examined showed similar performance in identifying patients at high risk for GIB after being prescribed antithrombotic agents. Two models (RegCox and XGBoost) performed modestly better than the HAS-BLED score. A prospective evaluation of the RegCox model compared with HAS-BLED may provide a better understanding of the clinical impact of improved performance.

Fewer gastrointestinal bleeds with ticagrelor and prasugrel compared with clopidogrel in patients with acute coronary syndrome following percutaneous coronary intervention.

BACKGROUND: Gastrointestinal bleeding (GIB) frequently occurs following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) with the prescription of P2Y12 inhibiting antiplatelet agents. Compared with clopidogrel, the newer P2Y12 inhibitors lower major adverse cardiac events with similar or possibly higher major bleeding events. The comparative GIB rates of these medications remain poorly understood. AIM: To compare GIB rates associated with clopidogrel, prasugrel and ticagrelor using national medical and pharmacy claims data from privately insured and Medicare Advantage enrollees . METHODS: Propensity score and inverse probability treatment weighting were used to balance baseline characteristics among treatment groups. The 1-year GIB risk was calculated using weighted Cox proportional hazard models and expressed as hazard ratios (HR) with 95% confidence intervals (CI) and number needed to harm (NNH). RESULTS: We identified 37 019 patients with ACS (non-ST elevation ACS [NSTE-ACS] and ST-elevation myocardial infarction [STEMI]) within 14 days of a PCI (mean age 63 years and 70% male). Clopidogrel prescription was most common (69%) with prasugrel (16%) and ticagrelor (14%) prescribed less frequently. When compared with clopidogrel, ticagrelor was associated with a 34% risk reduction (HR 0.66; 95% CI: 0.54-0.81) in GIB overall and with NSTE-ACS, and a 37% GIB risk reduction (HR 0.63; 95% CI: 0.42-0.93) in STEMI patients. When compared with clopidogrel, prasugrel was associated with a 21% risk reduction (HR 0.79; 95% CI: 0.64-0.97) overall, a 36% GIB risk reduction (HR 0.64; 95% CI: 0.49-0.85) in STEMI patients but no reduction of GIB risk in NSTE-ACS patients. CONCLUSIONS: In the first year following PCI, ticagrelor or prasugrel are associated with fewer GIB events than clopidogrel.

Successful Use of Intragastric Balloon Therapy as a Bridge to Heart Transplantation.

Obesity is an important limiting factor for heart transplantation (HT) in patients with congestive heart failure (CHF). Achieving substantial weight loss is challenging in this population due to activity limitations and fluid retention. Endoscopic bariatric therapies (EBTs) including intragastric balloons (IGB) are effective primary weight loss therapies. IGBs have also been successfully utilized as a bridge therapy prior to liver transplantation and, in one case report, prior to HT. Potential advantages of IGBs in this population include low bleeding risk and less invasiveness as compared to other EBTs and surgery. We report the successful use of IGB as a bridge therapy in two patients with class II obesity and end-stage CHF requiring left ventricular assist devices (LVAD), anticoagulation, antiplatelet, and inotrope therapy.

Risk of Gastrointestinal Bleeding Increases With Combinations of Antithrombotic Agents and Patient Age.

BACKGROUND & AIMS: The safety of different antithrombotic strategies for patients with 1 or more indication for antithrombotic drugs has not been determined. We investigated the risk and time frame for gastrointestinal bleeding (GIB) in patients prescribed different antithrombotic regimens. We proposed that risk would increase over time and with combination regimens, especially among elderly patients. METHODS: We performed a retrospective analysis of nationwide claims data from privately insured and Medicare Advantage enrollees who received anticoagulant and/or antiplatelet agents from October 1, 2010, through May 31, 2017. Patients were stratified by their prescriptions (anticoagulant alone, antiplatelet alone, or a combination) and by their primary diagnosis (atrial fibrillation, ischemic heart disease, or venous thromboembolism). The 1-year GIB risk was estimated using parametric time-to-event survival models and expressed as annualized risk and number needed to harm (NNH). RESULTS: Our final analysis included 311,211 patients (mean ages, 67 years for monotherapy and 69.8 years for combination antithrombotic therapy). There was no significant difference in the proportion of patients with bleeding after anticoagulant or antiplatelet monotherapy (∼3.5%/year). Combination antithrombotic therapy increased GIB risk compared with anticoagulant (NNH, 29) or antiplatelet (NNH, 31) monotherapy, regardless of the patients' diagnosis or time point analyzed. Advancing age was associated with increasing 1-year probability of GIB. Patients prescribed combination therapy were at the greatest risk for GIB, especially after the age of 75 years (GIB occurred in 10%-17.5% of patients/y). CONCLUSIONS: In an analysis of nationwide insurance and Medicare claims data, we found GIB to occur in a higher proportion of patients prescribed combinations of anticoagulant and antiplatelet agents compared with monotherapy. Among all drug exposure categories and cardiovascular conditions, the risk of GIB increased with age, especially among patients older than 75 years.

Antiplatelets, anticoagulants, and colonoscopic polypectomy.

The management of antiplatelet and anticoagulant (ie, antithrombotic) agents is challenging in the periendoscopic setting. In this state-of-the-art update, we review current best practice recommendations focusing on the risk of immediate and delayed postpolypectomy bleeding in the context of drug discontinuation (ie, temporary interruption) and drug continuation. The data regarding polypectomy technique (cold snare vs conventional thermal-based) and prophylactic placement of hemostatic clips are evaluated to assess whether these endoscopic techniques are beneficial in reducing postpolypectomy bleeding. Finally, clinical takeaways are provided to facilitate safer polypectomy among patients on antiplatelet and anticoagulant agents.

Management of Nonvariceal Upper Gastrointestinal Bleeding: Guideline Recommendations From the International Consensus Group.

Description: This update of the 2010 International Consensus Recommendations on the Management of Patients With Nonvariceal Upper Gastrointestinal Bleeding (UGIB) refines previous important statements and presents new clinically relevant recommendations. Methods: An international multidisciplinary group of experts developed the recommendations. Data sources included evidence summarized in previous recommendations, as well as systematic reviews and trials identified from a series of literature searches of several electronic bibliographic databases from inception to April 2018. Using an iterative process, group members formulated key questions. Two methodologists prepared evidence profiles and assessed quality (certainty) of evidence relevant to the key questions according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. Group members reviewed the evidence profiles and, using a consensus process, voted on recommendations and determined the strength of recommendations as strong or conditional. Recommendations: Preendoscopic management: The group suggests using a Glasgow Blatchford score of 1 or less to identify patients at very low risk for rebleeding, who may not require hospitalization. In patients without cardiovascular disease, the suggested hemoglobin threshold for blood transfusion is less than 80 g/L, with a higher threshold for those with cardiovascular disease. Endoscopic management: The group suggests that patients with acute UGIB undergo endoscopy within 24 hours of presentation. Thermocoagulation and sclerosant injection are recommended, and clips are suggested, for endoscopic therapy in patients with high-risk stigmata. Use of TC-325 (hemostatic powder) was suggested as temporizing therapy, but not as sole treatment, in patients with actively bleeding ulcers. Pharmacologic management: The group recommends that patients with bleeding ulcers with high-risk stigmata who have had successful endoscopic therapy receive high-dose proton-pump inhibitor (PPI) therapy (intravenous loading dose followed by continuous infusion) for 3 days. For these high-risk patients, continued oral PPI therapy is suggested twice daily through 14 days, then once daily for a total duration that depends on the nature of the bleeding lesion. Secondary prophylaxis: The group suggests PPI therapy for patients with previous ulcer bleeding who require antiplatelet or anticoagulant therapy for cardiovascular prophylaxis.

New clinical paradigms for treating and preventing antiplatelet gastrointestinal bleeding.

PURPOSE OF REVIEW: To quantify antiplatelet-related gastrointestinal bleeding (GIB), characterize patients at greatest risk and summarize risk-management strategies emphasizing evolving knowledge in acute management of antiplatelet-related bleeding. RECENT FINDINGS: New paradigms for acute management of antiplatelet-related GIB exist in the domains of resuscitation and the transfusion of blood products, strategic use of proton pump therapy and identification and eradication of Helicobacter pylori. This review will also highlight the importance of prompt resumption of cardiac aspirin and dual antiplatelet therapy following endoscopic hemostasis to minimize the risk of future cardiac events. SUMMARY: This review will provide pragmatic strategies for the management of acute antiplatelet-related GIB. Emerging areas of clinical knowledge will be addressed and knowledge gaps requiring further research to inform clinical practice will be highlighted.