Bleeding Events In Patients Research Articles

Direct oral anticoagulants and warfarin safety in rural patients with obesity

BackgroundDirect oral anticoagulants (DOACs) are often used in patients with atrial fibrillation or flutter instead of warfarin and although supporting evidence is limited, available studies suggest this may be an acceptable route of care. Our study assessed the question: are DOACs as effective and safe as warfarin in patients with atrial fibrillation and class III obesity specifically in a rural population? MethodsA retrospective analysis was conducted by examining the first 6-12 months of therapy with a DOAC (apixaban or rivaroxaban) or warfarin in patients with weight >120kg or class III obesity. Events of interest, thrombosis and bleeding, were documented for analysis. The risk and odds of events of interest for both groups were calculated and compared. ResultsCharacteristics of both arms were similar (DOAC n=42; warfarin n=43). A lack of thrombosis events limited efficacy analysis. A total of 22 bleeds occurred with 8 in patients prescribed a DOAC (7 minor; 1 major) and 14 in those prescribed warfarin (12 minor; 2 major). Weight in kg (p<0.001), BMI (p=0.013) and HAS-BLED score (p=0.035) were predictive of a first bleeding event in patients prescribed warfarin. The odds ratio for any type of bleed on DOAC vs warfarin was 0.55 (0.180-1.681; 95% CI). ConclusionsIn patients with atrial fibrillation and class III obesity, regarding safety, DOACs appear to be non-inferior to warfarin during the first six to 12 months of therapy in our rural population – consistent with other analyses; however, the lack of thrombosis events limited the efficacy analysis.

Incidence, Predictors and Associations Between In-Hospital Bleeding and Adverse Events in Patients with Acute Coronary Syndrome Above 75 Years of Age – The Real-World Scenario

Background: Bleeding events in patients with acute coronary syndrome (ACS) are associated with poor outcomes. Risk factors and their associations with in-hospital events in older patients with ACS are not fully understood, because older patients with ACS are often excluded from randomized controlled studies. Methods: We enrolled 962 patients with ACS above 75 years of age treated at our center between January 2012 and December 2016. The incidence and risk factors for in-hospital bleeding events, as well as their associations with in-hospital adverse events were evaluated. Results: Bleeding complications were observed in 38 patients (4.1%). The most common bleeding site was the gastrointestinal tract (52.6%). Anemia (P=0.007), renal insufficiency (P=0.019), use of positive inotropic medicines (P=0.006) and elevated leukocyte count (P=0.046) were independent predictors of in-hospital bleeding after adjustment for age, sex, atrial fibrillation history and hypertension history. In-hospital mortality (28.9% vs. 2.4%, P&lt;0.001), stroke (5.3% vs. 0.5%, P&lt;0.001) and the prevalence of heart failure (39.5% vs. 16.3%, P&lt;0.001) were significantly higher in patients with than without bleeding. Conclusions: The incidence of in-hospital bleeding was 4.1% in patients with ACS above 75 years of age in this cohort. Independent risk factors for in-hospital bleeding events included anemia, renal insufficiency and elevated leucocyte count. Bleeding events were strongly associated with in-hospital adverse events.

PS-C05-5: CLINICAL IMPACT OF CREDO-KYOTO RISK SCORE ON IN-HOSPITAL BLEEDING IN PATIENTS WITH ACUTE CORONARY SYNDROME

Background: CREDO-Kyoto bleeding risk score was developed to predict the post-discharge bleeding events in patients with percutaneous coronary intervention. However, there were limited reports of the effectiveness of this score to predict the in-hospital bleeding events in patients with acute coronary syndrome (ACS). Methods: We evaluated 562 consecutive ACS patients in Saga university hospital between 2014 and 2019. Primary outcome was major bleeding during hospitalization. Major bleeding was defined as the GUSTO moderate/severe bleeding. Patients were classified into three groups according to the CREDO-Kyoto bleeding risk score (low, intermediate and high). Results: Major bleeding events occurred in 12.1% of all patients during hospitalization. Patients in the high risk group (n = 22) had significantly higher incidence of major bleeding than those in the intermediate (n = 113) and the low risk groups (n = 427) (22.7%, 18.6%, versus 9.8%, respectively, p = 0.02). Multivariate analysis showed that intermediate and high risk groups were independent predictors for the in-hospital major bleeding. Conclusions: CREDO-Kyoto risk score successfully identified high risk ACS patients for the major bleeding during hospitalization.

Impact of the Japanese Version of High Bleeding Risk Criteria on Clinical Outcomes in Patients with ST-segment Elevation Myocardial Infarction.

Bleeding complications are often observed in patients with ST-segment elevation myocardial infarction (STEMI). Although the Japanese version of the high bleeding risk criteria (J-HBR) were established, it has not been sufficiently validated in patients with STEMI. This retrospective study aims to examine whether J-HBR is associated with cardiovascular and bleeding events in patients with STEMI. We included 897 patients with STEMI and divided them into the J-HBR group (n=567) and the non-J-HBR group (n=330). The primary endpoint was the major adverse cardiovascular events (MACE), defined as the composite of all-cause death, non-fatal myocardial infarction, ischemic stroke, and systemic embolism. Another primary endpoint was total bleeding events defined as type 3 or 5 bleeding events as defined by the Bleeding Academic Research Consortium . During the median follow-up duration of 573 days, 187 MACE and 141 total bleeding events were observed. The Kaplan-Meier curves showed that MACE and total bleeding events were more frequently observed in the J-HBR group than in the non-J-HBR group (p＜0.001). Multivariate Cox hazard analysis revealed that after controlling for multiple confounding factors, the J-HBR group was significantly associated with MACE (hazard ratio [HR] 4.676, 95% confidence interval (CI) 2.936-7.448, p＜0.001) and total bleeding events (HR 6.325, 95% CI 3.376-11.851, p＜0.001). J-HBR is significantly associated with MACE and total bleeding events in patients with STEMI. This study validated J-HBR as a risk marker for bleeding events and suggests J-HBR as a potential risk marker for MACE in patients with STEMI.

Evaluation of Patient Characteristics Linked to Major Bleeding Events in Patients Prescribed Direct Oral Anticoagulants.

Direct oral anticoagulants (DOACs) demonstrated similar efficacy and lower risk of intracranial hemorrhage than warfarin in patients with atrial fibrillation and venous thromboembolism. Given the lack of data identifying risk factors in patients who bled while on a DOAC, we sought to investigate these characteristics. This retrospective chart review was approved by the Mass General Brigham Institutional Review Board and assessed patients who experienced bleeding events while on DOAC therapy from 6/1/2015 to 7/1/2020. Patient characteristics were evaluated, including age, sex, body mass index (BMI), renal function, concomitant therapies, and baseline comorbidities. Eighty-seven patients were included for analysis, with a median age of 75.8 years. Most patients were female (51.7%) and 24 (27.6%) had a BMI >30. At time-of-event, 21 patients (24.1%) had acute kidney injury. Thirty-three patients (37.9%) were on concomitant antiplatelet therapy (APT), with 31 (35.6%) on single APT and 2 on dual APT. Pertinent comorbidities included hypertension (74.7%), ischemic cerebrovascular accident (28.7%), thyroid abnormality (23.0%), active cancer (14.9%), and anemia (13.8%). Eleven patients (12.6%) had a prior bleeding event. Most patients were on apixaban (69.0%) for the indication of stroke prevention in nonvalvular atrial fibrillation/flutter (72.4%). FDA-approved dosing was used in most patients (92.0%), and all deviations reflected underdosing. Most bleeding events were defined as major (95.4%), occurred at a critical organ site (72.4%), and developed spontaneously (58.6%). These data provide insight into characteristics of patients who experience bleeding events while on DOAC therapy. Understanding these potential risk factors may optimize the safe use of these agents.

Predictors of bleeding events in acute decompensated heart failure patients with antithrombotic therapy: AURORA study.

Heart failure (HF) is reported to be one of the major risks of bleeding events. On the other hand, HF patients frequently receive anticoagulants or antiplatelet therapy to manage various co-morbidities. However, predictors of bleeding events in patients with HF have rarely been reported. This study aimed to evaluate the predictors of bleeding events and relationship between bleeding events and HF re-hospitalizations. We included 1660 acute decompensated heart failure (ADHF) patients from the AURORA registry between January 2015 and December 2020. A total of 1429 patients were excluded because of history of HF admission, missing echocardiographic data at discharge, lost to follow-up, haemodialysis and no antithrombotic drugs. Finally, we evaluated 231 patients from AURORA registry. The bleeding events were defined as Type 2 to 5 bleeding according to the Bleeding Academic Research Consortium definition. We divided our patients into the bleeding group and non-bleeding group. We compared the baseline characteristics, medications, laboratory data, and echocardiographic data between the two groups. Median age was 78 (IQR 71-82) years old and male accounted for 59%. Approximately half of the patients had an antiplatelet therapy and 70% had an anticoagulant therapy. During a median follow-up of 651 (IQR 357-1139) days, 32 patients (13.8%) suffered from bleeding events. The major driver of the registered events was gastrointestinal bleeding (n=21, 65.6%), and the other events were cerebral bleeding (n=4, 12.5%), intraarticular bleeding (n=2, 6.3%), urogenital bleeding (n=2, 6.3%), haemorrhagic pericardial effusions (n=1, 3.1%), subcutaneous hematomas (n=1, 3.1%), and haemothorax (n=1, 3.1%). There was a significantly lower haemoglobin level (P<0.01), higher proportion of inferior vena cava (IVC) diameter ≥21mm (P<0.01), and higher furosemide equivalent doses per kilogram (P<0.01) in the bleeding group than non-bleeding group. A multivariate analysis revealed an equivalent dose of furosemide per kilogram ≥0.66mg/kg (hazard ratios (HR) of 2.64, 95% confidence interval (CI) 1.26-5.68, P=0.01), haemoglobin ≤10.3g/dL (HR of 2.43, 95% CI 1.14-5.03, P=0.02), and IVC diameter ≥21mm (HR of 2.79, 95% CI 1.16-6.29, P=0.02) were independently associated with bleeding events. The Kaplan-Meier analysis showed that HF re-hospitalization rates were higher in the bleeding group than non-bleeding group (P=0.04). High doses of oral loop diuretics, IVC dilatation, and anaemia were predictors of bleeding events in patients hospitalized with ADHF patients. In addition, bleeding events were associated with HF re-hospitalizations.

Association between liver fibrosis and thrombotic or bleeding events in acute coronary syndrome patients

BackgroundThe prognostic implication of liver fibrosis in acute coronary syndrome (ACS) patients are scarce. We sought to evaluate whether liver fibrosis scores (LFS) were associated with thrombotic or bleeding events in patients with acute coronary syndrome.MethodsWe included 6386 ACS patients who underwent percutaneous coronary intervention (PCI). This study determined liver fibrosis with aspartate aminotransferase to platelet ratio index (APRI), aspartate aminotransferase to alanine aminotransferase ratio (AST/ALT ratio), Forns score, and nonalcoholic fatty liver disease fibrosis score (NFS). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause mortality (ACM), myocardial infarction (MI), and ischemic stroke (IS).ResultsDuring the follow-up, 259 (4.06%) MACCE and 190 (2.98%) bleeding events were recorded. As a continuous variable or a categorical variable stratified by the literature-based cutoff, LFS was positively associated with MACCE (p > 0.05) but not with bleeding events. Compared with subjects with low APRI scores, AST/ALT ratio scores, Forns scores, and NFS scores, subjects with high scores had a 1.57- to 3.73-fold increase risk of MACCE after adjustment (all p < 0.05). The positive relationship between LFS and MACCE was consistent in different subgroups.ConclusionsIn ACS patients, increased LFS predicted an elevated risk of thrombotic events but not bleeding. LFS may contribute to thrombotic risk stratification after ACS.

Drug-drug Interactions between Warfarin and Antimicrobials: A Systematic Review

Introduction: Warfarin is a highly effective oral anticoagulant; however, its use is confined due to a valid concern about bleeding. This systematic review investigates the drug-drug interactions that may occur in patients on warfarin therapy and the use of antimicrobials.&#x0D; Methodology: PubMed, Web of Science, Science Direct, EBSCO, and Cochrane library were searched. Study articles were screened by title and abstract using Rayyan QCRI then a full-text assessment was conducted.&#x0D; Results: Eleven studies were included, with a total of 83438 patients. The included studies have reported different antibiotics were associated with bleeding events in patients on warfarin therapy. Three studies associated reported GIT bleeding. Older adults and patients who underwent valve replacement surgery and were on warfarin therapy were found to have an increase in INR with associated antibiotic use.&#x0D; Conclusion: Patients on warfarin run the risk of a variety of drug interactions. Most interactions but not all—increase the risk of bleeding, and the majority of these are linked to higher international normalised ratios. The good news for doctors is that most common drug interactions with warfarin are triggered by a small number of well-known drug classes, and their effects are shown through a small number of pathways, many of which are clear. The risk of harm brought on by drug interactions can be decreased by being aware of these guidelines, using thoughtful prescription practises, and exercising judicious monitoring when new medications are added to regimens containing warfarin.

Rivaroxaban in Patients With Atrial Fibrillation Who Underwent Percutaneous Coronary Intervention in Clinical Practice

Little is known about the efficacy and safety of rivaroxaban in patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI) in clinical practice. We therefore conducted a prospective observational study to determine the rate of ischemic, embolic, and bleeding events in patients with AF and PCI treated with rivaroxaban in a real-world experience. The RIVA-PCI ("rivaroxaban in patients with AF who underwent PCI") (clinicaltrials.gov NCT03315650) is a prospective, noninterventional, multicenter study with a follow-up until 14months, including patients with AF who underwent PCI discharged with rivaroxaban. Between January 2018 and March 2020, 700 patients with PCI treated with rivaroxaban (elective in 50.1%, non-ST-elevation acute coronary syndrome 43.0%, ST-elevation myocardial infarction in 6.9%) were enrolled at 51 German hospitals. After PCI, a dual antithrombotic therapy consisting of rivaroxaban and a P2Y12 inhibitor was administered in 70.7% and triple antithrombotic therapy in 27.9%, respectively. Follow-up information could be obtained in 695 patients (99.3%). Rivaroxaban has been stopped prematurely in 21.6% of patients. Clinical events under rivaroxaban during the 14-month follow-up compared with those observed in the PIONEER-AF PCI trial included cardiovascular death (2.0% % vs 2.0%), myocardial infarction (0.9% vs 3.0%), stent thrombosis (0.2% vs 0.8%), stroke (1.3% vs 1.3%), International Society on Thrombosis and Haemostasis major (4.2% vs 3.9%), and International Society on Thrombosis and Haemostasis nonmajor clinically relevant bleeding (15.3% vs 12.9%). Therefore, in this real-world experience, rivaroxaban in patients with AF who underwent PCI is associated with ischemic and bleeding event rates comparable with those observed in the randomized PIONEER-AF PCI trial.

Performance of the HAS-BLED, ORBIT, and ATRIA Bleeding Risk Scores on a Cohort of 399 344 Hospitalized Patients With Atrial Fibrillation and Cancer: Data From the French National Hospital Discharge Database.

Background The association between cancer types and specific bleeding events in patients with atrial fibrillation has been scarcely investigated. Also, the performance of bleeding risk scores in this high-risk subgroup of patients is unclear. We investigated the rate of any bleeding, intracranial hemorrhage, major bleeding, and gastrointestinal bleeding according to cancer types in patients with atrial fibrillation. We also tested the predictive value of HAS-BLED, ATRIA, and ORBIT bleeding risk scores. Methods and Results Observational retrospective cohort study including hospitalized patients with atrial fibrillation and cancer from the French National Hospital Discharge Database (Programme de Medicalisation des Systemes d'Information) from January 2010 to December 2019. Major bleeding was defined according to Bleeding Academic Research Consortium definitions. Patients with HAS-BLED ≥3, ATRIA ≥5, or ORBIT ≥4 were classified as at high bleeding risk. Receiver operating characteristic analysis for each score against any bleeding, major bleeding, gastrointestinal bleeding, and intracranial hemorrhage was performed. Areas under the curve (AUCs) were then compared. We included 399 344 patients. Mean age was 77.9±10.2 years, and 63.2% were men. The highest intracranial hemorrhage rates were found in leukemia (1.89%/year), myeloma (1.52%/year), lymphoma and liver (1.45%/year), and pancreas cancer (1.41%/year). Receiver operating characteristic analysis showed that ORBIT score predicted best for any bleeding. In addition, ORBIT score ≥4 had the highest predictivity for major bleeding (AUC, 0.805), followed by HAS-BLED ≥3 and ATRIA ≥5 (AUCs, 0.716 and 0.700, respectively). HAS-BLED and ORBIT performed best for intracranial hemorrhage (AUCs, 0.744 and 0.742 for continuous scores, respectively), better than ATRIA (AUC, 0.635). For gastrointestinal bleeding, ORBIT ≥4 had the highest predictivity (AUC, 0.756), followed by the HAS-BLED ≥3 (AUC, 0.702) and ATRIA ≥5 (AUC, 0.662). Conclusions Some cancer types carry a greater bleeding risk in patients with atrial fibrillation. The identification and management of modifiable bleeding risk factors is crucial in these patients, as well as to flag up high bleeding risk patients for early review and follow-up.

A Preliminary Analysis of Athn 16: Safety of Coagulation Factor VIIa (recombinant)-Jncw for the Treatment of Bleeding Events in Patients with Congenital Hemophilia a or B with Inhibitors

Background: Eptacog beta (rFVIIa-jncw) (brand name SEVENFACT®) was approved by the U.S. Food and Drug Administration (FDA) in 2020 for the treatment of bleeding events (BEs) in individuals 12 years of age and older with hemophilia A or B (HAB) complicated by inhibitors. ATHN 16: Safety of Coagulation Factor VIIa (recombinant)-jncwforthe Treatment of Bleeding Events in Patients with Hemophilia A or B with Inhibitors was designed to collect real-world evidence on the safety of eptacog beta. Objective: To evaluate the safety of eptacog beta when used to treat BEs in participants with HAB with inhibitors with or without FDA-approved prophylactic treatment. Methods: ATHN 16 (NCT04647227) is a phase IV, United States-centric multicenter, open-label safety study enrolling participants with HAB with inhibitors aged 12 years and older, who are either on an FDA-approved prophylaxis and at risk of experiencing a breakthrough BE or who are not on prophylactic treatment and may need to control a BE. Exclusion criteria include any bleeding disorder in addition to HAB, a known hypersensitivity to eptacog beta or rabbit proteins, or the inability to provide informed consent. The maximum study duration for any participant in the study will be up to 2 years from the time of enrollment. Safety of eptacog beta is evaluated based on events included in the European Haemophilia Safety Surveillance (EUHASS) protocol, including allergic or other acute events, treatment-emergent side effects, transfusion-transmitted infections, inhibitor (FVII) development, thrombosis, cardiovascular events, malignancies, neurological events, and deaths. After informed consent is obtained, demographics, bleeding disorder history, inhibitor history, baseline medical and surgical history are recorded for the baseline data. Each participant receives nine 75 µg/kg doses of eptacog beta supplied by the study funder. Eptacog beta is administered by the participant or by study staff at the time of a BE. The doses and duration of treatment are determined at the discretion of the treating physician. BE details including timing of BE, any treatments associated with the BE (including eptacog beta) and timing of resolution of the event, are collected as well as surgical procedures, EUHASS events, adverse events of special interest (AESIs), and serious adverse events (SAEs). Results: At the time of abstract submission, ATHN 16, having received central IRB approval, is rolled out to ATHN-affiliated sites across the United States. The study is currently open to enrollment at 11 sites and an additional 21 sites are proceeding with start-up approvals. A total of seven participants have been enrolled. One BE, unrelated to study product, has been reported. One SAE, unrelated to study product, has been reported. Conclusions: To date, a total of seven participants have enrolled in ATHN 16. One bleeding event has been treated with eptacog beta. The results will be updated, and all safety endpoints will be updated prior to the December 2022 meeting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Abstract 10844: Black Race and Risk of Bleeding Events in Patients With Durable Left Ventricular Assist Devices

Introduction: An analysis from the MOMENTUM 3 trial showed that black patients have an increased risk of bleeding compared to white patients. We sought to examine racial differences in the risk of long term bleeding (up to 3 years) in patients with cf-LVADs using the INTERMACS database. Hypothesis: Black race is associated with an increased risk of bleeding events after cf-LVAD. Methods: We included 11,457 patients from the INTERMACS registry, who were implanted with primary CF-LVAD between 2012-2017. Using a cox proportional hazards model, we assessed the relationship between race and bleeding events up to 3 years post LVAD implantation after adjusting for covariates*. Analysis was started at 3 months post implantation to focus on long-term bleeding risk rather than early, post-operative bleeding. These bleeding events were stratified for the two major types of bleeding, GI bleeding (GIB) and intracranial hemorrhage (ICH). Results: This study included 2884 black patients (25.8%) and 8505 non-black patients (74.2%). Black patients tended to be younger (52.2 vs 58.6 yr p&lt;0.001) with more women (30.9% vs 17.7% p&lt;0.001) when compared to non-black patients. There were 1442 black patients who had a bleeding event vs 3972 non-black patients (50.0% vs 46.7% p=0.007) over 3 years of follow up (Fig 1). After adjusting for age, sex, and other covariates*, we found that black patients were more likely to have any bleeding event post LVAD implantation compared to non-black patients (adj HR 1.19 p&lt;0.0001). When stratified by type of bleeding, the risk of ICH was similar between the two groups (10.8% vs 9.2%, adj HR 1.12, p 0.35), but the risk of GIB was higher among black vs non-black patients (30.9% vs 29.6%; adj HR 1.36, p&lt;0.0001). Conclusions: Black patients have a higher risk of long term bleeding and specifically GIB after LVAD implantation. Further studies are warranted to elucidate this relationship and potential clinical implications including anticoagulation strategies.

Abstract 10222: Impact of Bleeding Event for New Cancer Diagnosis in Patients With Antiplatelet Therapy After Percutaneous Coronary Intervention

Background: It has been reported that the bleeding event represents unmasking of an occult cancer in anticoagulated patients with atrial fibrillation. However, the impact of bleeding event in patients with antiplatelet therapy after percutaneous coronary intervention (PCI) for new cancer diagnosis remains unclear. Methods and Results: Consecutive 1796 patients with coronary artery disease who underwent PCI and taking antiplatelet therapy were enrolled. Patients taking oral anticoagulants were excluded, and relationships between bleeding event and new cancer diagnosis were examined. Among 1565 patients, 189 (12.0%) experienced any bleeding events defined as Bleeding Academic Research Consortium (BARC) type-2/3/5 bleeding, 78 (4.9%) experienced minor bleeding events defined as BARC type-2 bleeding, and 116 (7.4%) were diagnosed with new cancer during a mean follow-up period of 1528 days. Patients with any bleeding were older (71.3 vs. 68.8 years, P = 0.005) and had higher prevalence of being at Academic Research Consortium criteria for high bleeding risk (62.4% vs. 43.8%, P &amp;lt; 0.001) than those without bleeding event. Of 189 patients with any bleeding and 78 patients with minor bleeding events, 31 (16.4%) and 16 (20.5%) were diagnosed with new cancer, respectively. In the univariate Cox proportional hazard analysis, the incidence of new cancer diagnosis was higher in patients with any bleeding and minor bleeding events than those without bleeding event (hazard ratio [HR] 3.19, P &amp;lt; 0.001 and HR 5.70, P &amp;lt; 0.001, respectively). In the multivariate analysis after adjusting for confounding factors, any bleeding and minor bleeding events were the independent predictors of new cancer diagnosis (HR 2.27, P = 0.003 and HR 3.93, P &amp;lt; 0.001, respectively). In addition, any gastrointestinal bleeding and minor bleeding events were associated with higher rates of new gastrointestinal cancer diagnosis (HR 4.46, P = 0.041 and HR 6.73, P = 0.009, respectively). Conclusion: In patients with antiplatelet therapy after PCI, any bleeding and minor bleeding events were associated with subsequent new cancer diagnosis. Even minor bleeding should be taken care as the first manifestation of underlying cancer during antiplatelet therapy.

Sex differences and risk factors for bleeding in Alagille syndrome

Spontaneous bleeds are a leading cause of death in the pediatric JAG1‐related liver disease Alagille syndrome (ALGS). We asked whether there are sex differences in bleeding events in patients, whether Jag1Ndr/Ndr mice display bleeds or vascular defects, and whether discovered vascular pathology can be confirmed in patients non‐invasively. We performed a systematic review of patients with ALGS and vascular events following PRISMA guidelines, in the context of patient sex, and found significantly more girls than boys reported with spontaneous intracranial hemorrhage. We investigated vascular development, homeostasis, and bleeding in Jag1Ndr/Ndr mice, using retina as a model. Jag1Ndr/Ndr mice displayed sporadic brain bleeds, a thin skull, tortuous blood vessels, sparse arterial smooth muscle cell coverage in multiple organs, which could be aggravated by hypertension, and sex‐specific venous defects. Importantly, we demonstrated that retinographs from patients display similar characteristics with significantly increased vascular tortuosity. In conclusion, there are clinically important sex differences in vascular disease in ALGS, and retinography allows non‐invasive vascular analysis in patients. Finally, Jag1Ndr/Ndr mice represent a new model for vascular compromise in ALGS.

Abstract 9789: Geriatric Nutritional Risk Index Predicts Bleeding Event in Patients With Heart Failure

Introduction: The relationship between malnutrition and bleeding event has been unclear in patients with heart failure (HF). Method and Results: We evaluated the nutritional status of patients with HF (n = 2,044) using Geriatric Nutritional Risk Index (GNRI). The primary endpoint was composite bleeding event of hemorrhagic stroke or gastrointestinal bleeding. According to the survival classification and regression tree analysis, the accurate cut-off point of GNRI for predicting the primary endpoint was 106.2. We divided patients into two groups based on GNRI levels: the High GNRI group (GNRI ≥ 106.2, n = 606, 29.6%) and the Low GNRI group (GNRI &lt; 106.2, n = 1,438, 70.4%), and compared patients’ characteristics and prognosis between the two groups. The Low GNRI group showed higher age (72.0 vs. 63.0 years, P &lt; 0.001) and lower prevalence of male sex (56.9% vs. 64.5%, P = 0.001) than the High GNRI group. There were no differences in use of antiplatelet agents and anticoagulants between the groups. In laboratory data, levels of B-type natriuretic peptide were higher in the Low GNRI group (321.1 vs. 111.6 pg/mL, P &lt; 0.001). Left ventricular ejection fraction was comparable between the groups. The Kaplan-Meier analysis demonstrated that bleeding event rates were higher in the Low GNRI group than in the High GNRI group (Figure, log-rank P &lt; 0.001). The multivariable Cox proportional hazard analysis revealed that the Low GNRI was independently associated with bleeding events (hazard ratio 1.795, P = 0.047). Conclusions: Malnutrition assessed by GNRI predicts bleeding events in patients with HF.

Incidence of stroke, systemic embolism and bleeding events in patients without anticoagulation based on real-world data in Japan: a retrospective cohort study

ObjectivesTo examine the incidence of stroke or systemic embolic events (SSEs) and bleeding events in untreated patients with non-valvular atrial fibrillation (NVAF) after widespread use of direct oral anticoagulant agents...

Socioeconomic factors and bleeding events in patients with incident atrial fibrillation: A Finnish nationwide cohort study.

Low socioeconomic status has been associated with higher risk of ischemic stroke and death in patients with atrial fibrillation (AF). However, whether socioeconomic status affects risk of bleeding events is unknown. We assessed the hypothesis that low income and educational attainment are associated with higher risk of bleeding in patients with AF. The registry-based FinACAF study covers all patients with AF in Finland during 2007-2018. Patients were divided into income quartiles and three categories based on their educational attainment. Outcomes of interest were the first-ever gastrointestinal (GI), intracranial (IC) and any bleeding. We identified 205 019 patients (50.9% female; mean age 72.3 (SD 13.4) years) with incident AF without prior bleeding. Mean follow-up time was 4.0 (SD 3.2) years, during which 25013 (12.2%) patients experienced first-ever any bleeding (incidence rate 3.07 (95% CI 3.03-3.10) /100 patient-years). Low income was independently associated with hazard of any bleeding as well as GI and IC bleeding (adjusted hazard ratios (HRs) comparing lowest vs highest income quartile: 1.13 (1.08-1.17), 1.32 (1.23-1.41) and 1.15 (1.06-1.24), respectively). Income-related bleeding disparities were larger among younger patients under 65years and among men. Education-related bleeding disparities were smaller than income related-disparities (adjusted HRs comparing lowest vs highest educational category: any bleeding 1.06 (1.02-1.11), GI bleeding 1.16 (1.08-1.24), IC bleeding 1.10 (0.93-1.09)). Patients with AF and low income are at higher risk of bleeding, especially GI bleeding.

Bleeding events among patients concomitantly treated with direct oral anticoagulants and macrolide or fluoroquinolone antibiotics.

Fluoroquinolones and macrolides may, due to a potential drug-drug interaction, increase the concentration of any concomitantly administered direct oral anticoagulant (DOAC) and thereby increase the risk of severe bleeding. However, clinical evidence for such an effect is scarce. The present study aimed to evaluate the association between the use of fluoroquinolones or macrolides and bleeding events in patients with concomitant DOAC use. This was a nationwide cohort study including 19 288 users of DOACs in 2008-2018 using information from Swedish national health registers. We compared the incidence of bleeding events associated with use of fluoroquinolones or macrolides using doxycycline as a negative control. Cox regression was used to calculate crude and adjusted hazard ratios (aHRs) in time windows of various length of follow-up after the start of antibiotic use. The incidence rates for fluoroquinolones and macrolides ranged from 12 to 24 and from 12 to 53 bleeding events per 100 000 patients in the investigated time windows. The aHRs (95% confidence interval) for use of fluoroquinolones and macrolides were 1.29 (0.69-2.44) and 2.60 (0.74-9.08) at the concomitant window, 1.31 (0.84-2.03) and 1.79 (0.75-4.29) at 30 days, and 1.34 (0.99-1.82) and 1.28 (0.62-2.65) at 150 days, respectively. With regard to fluoroquinolones, the present study suggests that the risk of bleeding when combined with DOACs, if any, is small. Codispensation of macrolides in patients on DOACs was not associated with an increased risk of bleeding. However, due to the small number of macrolide users, the results must be interpreted with caution.

Association of ischemic and bleeding events with mortality in patients with a recent acute myocardial infarction

Abstract Background/Introduction Duration and intensity of antithrombotic treatment after myocardial infarction should be individualized based on a patient's ischemic and bleeding risk [1,2]. While such strategies are typically based on calculations that give equal weight to both types of events, uncertainty remains regarding their relative importance. Purpose To describe the incidence of ischemic and bleeding events in patients with a recent myocardial infarction, to compare the association of an ischemic vs bleeding event with mortality and to assess whether this association had changed over the past two decades. Methods Patients with acute myocardial infarction enrolled in the SWEDEHEART registry and discharged alive with antithrombotic treatment (aspirin, P2Y12 inhibitor, or oral anticoagulant) from January 2012 to December 2017 were followed from discharge until an ischemic event (recurrent myocardial infarction or ischemic stroke) or bleeding event. Cox regression adjusted for demographic factors, comedications and comorbidities, was used to estimate hazard ratios (HR) for time to death after an ischemic and bleeding event as compared with no event (in a model using time-varying exposure definition) and for an ischemic vs bleeding event in a direct comparison. We then assessed whether the adjusted HR for mortality of an ischemic vs bleeding event had changed across three time-periods (1997–2000, 2001–2011 and 2012–2017) by using an interaction term between time period and type of event. Results From January 2012 until December 2017 86, 736 patients were discharged alive with antithrombotic treatment after a myocardial infarction. Of these, 4,039 patients experienced a first ischemic event (incidence rate 5.7 events per 100 person-years), and 3,399 a first bleeding event (incidence rate 4.8 events per 100 person-years). As compared with no event, both ischemic events (adjusted HR 4.16, 95% CI 3.91 to 4.43) and bleeding events (adjusted HR 3.43, 95% CI 3.17 to 3.71) were associated with an increased risk of death. In the direct comparison, ischemic events were associated with a higher risk of death than bleeding events (adjusted HR 1.27, 95% CI 1.15 to 1.40). There was no evidence of a change in the aHR across the three time periods (aHR; 1.17, 95% CI 1.02 to 1.35 in 1997–2000 and 1.18, 95% CI, 1.11 to 1.27 in 2001–2011, p for interaction between time period and type of event ≥0.646). Conclusion In this nationwide study of patients with a recent MI, post-discharge ischemic events were more common and associated with higher mortality risk as compared with bleeding events. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Swedish Heart and Lung FoundationSwedish Diabetes Foundation

Optimal protamine-to-heparin dosing ratio for the prevention of bleeding complications in patients undergoing TAVR – a multicentre experience

Abstract Background Despite major advances, transcatheter aortic valve replacement (TAVR) is associated with procedure-related vascular and bleeding complications, that have a significant impact on mortality. A recently published study has shown that heparin antagonization using protamine resulted in significantly lower rates of serious bleeding events in patients undergoing TAVR as compared to those without heparin reversal. However, the optimal protamine-to-heparin dosing ratio to prevent bleeding complications without increasing ischemic complications in patients undergoing TAVR is unknown. Accordingly, daily clinical practice varies between selective to routine administration of protamine in different dosing ratios. Purpose The aim of this observational multicentre study was to compare the safety and efficacy of two different protamine-to-heparin dosing ratios for the prevention of bleeding complications after TAVR. Methods The study included 1446 patients undergoing TAVR, of whom 623 (43.1%) received partial and 823 (56.9%) full heparin antagonization (0.4–0.6 mg versus 0.9–1.0 mg protamine/100 units of heparin). The indication for partial or full heparin antagonization was left to the discretion of the operator, who made the decision according to the patient's individual thrombotic and bleeding risk. The primary endpoint was a composite of 30-day mortality, life-threatening and major bleeding. Safety endpoints included stroke and myocardial infarction at 30 days. Results The overall study population had a mean age of 81.1±6.0 years; 47.9% were of female gender. The baseline characteristics were well balanced between the two groups. Full antagonization of heparin resulted in significantly lower rates of the primary endpoint as compared to partial heparin reversal (5.6 vs. 10.4%, p&amp;lt;0.01), mainly driven by lower rates of life-threatening (0.5 vs 1.6%, p=0.05) and major bleeding (3.2 vs 7.5%, p&amp;lt;0.01). The incidence of major vascular complications was significantly lower in patients with full heparin reversal (3.5 vs 7.5%, p&amp;lt;0.01), as presented in Figure 1. Accordingly, the post-interventional drop in hemoglobin level and the need for red-blood-cell transfusion was lower in patients receiving full as compared to partial heparin reversal (1.5±1.2 vs 1.7±1.2 g/dl, p&amp;lt;0.01; 10.4 vs 15.9%, p&amp;lt;0.01, respectively). Regarding safety endpoints, no differences were observed in the incidence of stroke and myocardial infarction between the groups (2.2 vs 2.6%, p=0.73 and 0.2 vs 0.4%, p=0.64, respectively). Multivariate regression analyses revealed that full antagonization of heparin (OR: 0.43 [95% CI: 0.24–0.81], p&amp;lt;0.01) was independently associated with the primary end point Conclusion Full heparin antagonization resulted in significantly lower rates of life-threatening and major bleeding after TAVR as compared to partial heparin reversal. The occurrence of stroke and myocardial infarction was low and comparable between both groups. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation).