Higher Risk Of Major Bleeding Research Articles

Performance of risk scores in predicting major bleeding in left ventricular assist device recipients: a comparative external validation

BackgroundImplantation of a left ventricular assist device (LVAD) is a crucial therapeutic option for selected end-stage heart failure patients. However, major bleeding (MB) complications postimplantation are a significant concern. ObjectivesWe evaluated current risk scores’ predictive accuracy for MB in LVAD recipients. MethodsWe conducted an observational, single-center study of LVAD recipients (HeartWare or HeartMate-3, November 2010-December 2022) in the Netherlands. The primary outcome was the first post-LVAD MB (according to the International Society on Thrombosis and Haemostasis [ISTH] and Interagency Registry for Mechanically Assisted Circulatory Support [INTERMACS], and INTERMACS combined with intracranial bleeding [INTERMACS+] criteria). Mortality prior to MB was considered a competing event. Discrimination (C-statistic) and calibration were evaluated for the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly score, Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke score, Anticoagulation and Risk Factors in Atrial Fibrillation score, Outpatient Bleeding Risk Index, venous thromboembolism score, atrial fibrillation score, and Utah Bleeding Risk Score (UBRS). ResultsOne hundred four patients were included (median age, 64 years; female, 20.2%; HeartWare, 90.4%; HeartMate-3, 9.6%). The cumulative MB incidence was 75.7% (95% CI 65.5%-85.9%) by ISTH and INTERMACS+ criteria and 67.0% (95% CI 56.0%-78.0%) per INTERMACS criteria over a median event-free follow-up time of 1916 days (range, 59-4521). All scores had poor discriminative ability on their intended prediction timeframe. Cumulative area under the receiving operator characteristic curve ranged from 0.49 (95% CI 0.35-0.63, venous thromboembolism-BLEED) to 0.56 (95% CI 0.47-0.65, UBRS) according to ISTH and INTERMACS+ criteria and from 0.48 (95% CI 0.40-0.56, Anticoagulation and Risk Factors in Atrial Fibrillation) to 0.56 (95% CI 0.47-0.65, UBRS) per INTERMACS criteria. All models showed poor calibration, largely underestimating MB risk. ConclusionCurrent bleeding risk scores exhibit inadequate predictive accuracy for LVAD recipients. There is a need for an accurate risk score to identify LVAD patients at high risk of MB who may benefit from patient-tailored antithrombotic therapy.

Direct oral anticoagulant-associated bleeding complications in patients with gastrointestinal cancer and venous thromboembolism

BackgroundDirect oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer. MethodsUsing the COMMAND VTE Registry-2 database, which is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020, we identified 1149 active cancer patients with DOACs (upper GI cancer: N = 88; lower GI cancer: N = 114; non-GI cancer: N = 947). The primary outcome was major bleeding during anticoagulation therapy, which was evaluated in the competing risk regression model. ResultsThe upper GI cancer group had a lower mean body weight, and most often had anemia. The cumulative 5-year incidence of major bleeding was higher in the upper GI cancer group (upper GI cancer: 22.4 %, lower GI cancer: 15.4 %, and non-GI cancer: 11.6 %, P = 0.015). The most frequent major bleeding site in the upper GI cancer group was the upper GI (53 %), followed by the lower GI (24 %). After adjusting for the confounders, the excess risk in upper GI cancer relative to non-GI cancer remained significant for major bleeding (adjusted subhazard ratio, 2.25; 95 %CI, 1.31–3.87, P = 0.003), but that in lower GI cancer was insignificant. ConclusionsUpper GI cancer, but not lower GI cancer, as compared to non-GI cancer was associated with a higher risk for major bleeding during anticoagulation therapy with DOACs.Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htmUnique identifier: UMIN000044816.

Anticoagulation for Patients With Concomitant Atrial Fibrillation and End-Stage Renal Disease: A Systematic Review and Network Meta-Analysis.

Concomitant atrial fibrillation and end-stage renal disease is common and associated with an unfavorable prognosis. Although oral anticoagulants have been well established to prevent thromboembolism, the applicability in patients under long-term dialysis remains debatable. The study aimed to determine the efficacy and safety of anticoagulation in the dialysis-dependent population. An updated network meta-analysis based on MEDLINE, EMBASE, and the Cochrane Library was performed. Studies published up to December 2022 were included. Direct oral anticoagulants (DOACs, dabigatran, rivaroxaban, apixaban 2.5/5 mg twice daily), vitamin K antagonists (VKAs), and no anticoagulation were compared on safety and efficacy outcomes. The outcomes of interest were major bleeding, thromboembolism, and all-cause death. A total of 42 studies, including 3 randomized controlled trials, with 185 864 subjects were pooled. VKAs were associated with a significantly higher risk of major bleeding than either no anticoagulation (hazard ratio [HR], 1.47; 95% CI, 1.34-1.61) or DOACs (DOACs versus VKAs; HR, 0.74 [95% CI, 0.64-0.84]). For the prevention of thromboembolism, the efficacies of VKAs, DOACs, and no anticoagulation were equivalent. Nevertheless, dabigatran and rivaroxaban were associated with fewer embolic events. There were no differences in all-cause death with the administration of VKAs, DOACs, or no anticoagulation. For dialysis-dependent populations, dabigatran and rivaroxaban were associated with better efficacy, while dabigatran and apixaban demonstrated better safety. No anticoagulation was a noninferior alterative, and VKAs were associated with the worst outcomes.

Characteristics of traumatic major haemorrhage in a tertiary trauma center

BackgroundMajor traumatic haemorrhage is potentially preventable with rapid haemorrhage control and improved resuscitation techniques. Although advances in prehospital trauma management, haemorrhage is still associated with high mortality. The aim of this study was to use a recent pragmatic transfusion-based definition of major bleeding to characterize patients at risk of major bleeding and associated outcomes in this cohort after trauma.MethodsThis was a retrospective cohort study including all trauma patients (n = 7020) admitted to a tertiary trauma center from January 2015 to June 2020. The major bleeding cohort (n = 145) was defined as transfusion of 4 units of any blood components (red blood cells, plasma, or platelets) within 2 h of injury. Univariate and multivariable logistic regression analyses were performed to identify risk factors for 24-hour and 30-day mortality post trauma admission.ResultsIn the major bleeding cohort (n = 145; 145/7020, 2.1% of the trauma population), there were 77% men (n = 112) and 23% women (n = 33), median age 39 years [IQR 26–53] and median Injury Severity Score (ISS) was 22 [IQR 13–34]. Blunt trauma dominated over penetrating trauma (58% vs. 42%) where high-energy fall was the most common blunt mechanism and knife injury was the most common penetrating mechanism. The major bleeding cohort was younger (OR 0.99; 95% CI 0.98 to 0.998, P = 0.012), less female gender (OR 0.66; 95% CI 0.45 to 0.98, P = 0.04), and had more penetrating trauma (OR 4.54; 95% CI 3.24 to 6.36, P = 0.001) than the rest of the trauma cohort. A prehospital (OR 2.39; 95% CI 1.34 to 4.28; P = 0.003) and emergency department (ED) (OR 6.91; 95% CI 4.49 to 10.66, P = 0.001) systolic blood pressure < 90 mmHg was associated with the major bleeding cohort as well as ED blood gas base excess < -3 (OR 7.72; 95% CI 5.37 to 11.11; P < 0.001) and INR > 1.2 (OR 3.09; 95% CI 2.16 to 4.43; P = 0.001). Emergency damage control laparotomy was performed more frequently in the major bleeding cohort (21.4% [n = 31] vs. 1.5% [n = 106]; OR 3.90; 95% CI 2.50 to 6.08; P < 0.001). There was no difference in transportation time from alarm to hospital arrival between the major bleeding cohort and the rest of the trauma cohort (47 [IQR 38;59] vs. 49 [IQR 40;62] minutes; P = 0.17). However, the major bleeding cohort had a shorter time from ED to first emergency procedure (71.5 [IQR 10.0;129.0] vs. 109.00 [IQR 54.0; 259.0] minutes, P < 0.001). In the major bleeding cohort, patients with penetrating trauma, compared to blunt trauma, had a shorter alarm to hospital arrival time (44.0 [IQR 35.5;54.0] vs. 50.0 [IQR 41.5;61.0], P = 0.013). The 24-hour mortality in the major bleeding cohort was 6.9% (10/145). All fatalities were due to blunt trauma; 40% (4/10) high energy fall, 20% (2/10) motor vehicle accident, 10% (1/10) motorcycle accident, 10% (1/10) traffic pedestrian, 10% (1/10) traffic other, and 10% (1/10) struck/hit by blunt object. In the logistic regression model, prehospital cardiac arrest (OR 83.4; 95% CI 3.37 to 2063; P = 0.007) and transportation time (OR 0.95, 95% CI 0.91 to 0.99, P = 0.02) were associated with 24-hour mortality.ResultsEarly identification of patients at high risk of major bleeding is challenging but essential for rapid definitive haemorrhage control. The major bleeding trauma cohort is a small part of the entire trauma population, and is characterized of being younger, male gender, higher ISS, and exposed to more penetrating trauma. Early identification of patients at high risk of major bleeding is challenging but essential for rapid definitive haemorrhage control.

Effectiveness and Safety of Edoxaban Compared With Apixaban in Elderly Patients With Nonvalvular Atrial Fibrillation: A Real-World Population-Based Cohort Study.

The very elderly (≥80 years) are at high risk of nonvalvular atrial fibrillation and thromboembolism. Given its recent approval, the comparative effectiveness and safety of edoxaban in this population, relative to the commonly used apixaban, remain unknown. Using the United Kingdom Clinical Practice Research Datalink, we identified a cohort of patients aged ≥80 with incident nonvalvular atrial fibrillation and newly treated with edoxaban or apixaban between 2015 and 2021. Cohort entry was defined as the first prescription for one of the 2 drugs. We used propensity score fine stratification and weighting for confounding adjustment. A weighted Cox proportional hazards model was used to estimate the hazard ratios (HR) with 95% CI of ischemic stroke/transient ischemic attack/systemic embolism (primary effectiveness outcome) and of major bleeding (primary safety outcome) associated with edoxaban compared with apixaban. We also assessed the risk of all-cause mortality and a composite outcome of ischemic stroke/transient ischemic attack, systemic embolism, gastrointestinal bleeding, and intracranial hemorrhage as secondary outcomes. The cohort included 7251 new-users of edoxaban and 39 991 of apixaban. Edoxaban and apixaban had similar incidence rates of thromboembolism (adjusted rates, 20.38 versus 19.22 per 1000 person-years; adjusted HR, 1.06 [95% CI, 0.89-1.26]), although the rates of major bleeding were higher with edoxaban (adjusted rates, 45.57 versus 31.21 per 1000 person-years; adjusted HR, 1.42 [95% CI, 1.26-1.61]). The risk of the composite outcome was 21% higher with edoxaban (adjusted HR, 1.21 [95% CI, 1.07-1.38]). All-cause mortality was similar between edoxaban and apixaban (adjusted HR, 1.04 [95% CI, 0.96-1.12]). In very elderly patients with nonvalvular atrial fibrillation, edoxaban resulted in similar thromboembolism prevention as apixaban, although it was associated with a higher risk of major bleeding. These findings may improve the management of nonvalvular atrial fibrillation by informing physicians on the choice of anticoagulant for this vulnerable population.

The optimal antithrombotic strategy for post-stroke patients with atrial fibrillation and extracranial artery stenosis—a nationwide cohort study

BackgroundIn post-stroke atrial fibrillation (AF) patients who have indications for both oral anticoagulant (OAC) and antiplatelet agent (AP), e.g., those with carotid artery stenosis, there is debate over the best antithrombotic strategy. We aimed to compare the risks of ischemic stroke, composite of ischemic stroke/major bleeding and composite of ischemic stroke/intracranial hemorrhage (ICH) between different antithrombotic strategies.MethodsThis study included post-stroke AF patients with and without extracranial artery stenosis (ECAS) (n = 6390 and 28,093, respectively) identified from the Taiwan National Health Insurance Research Database. Risks of clinical outcomes and net clinical benefit (NCB) with different antithrombotic strategies were compared to AP alone.ResultsThe risk of recurrent ischemic stroke was higher for patients with ECAS than those without (12.72%/yr versus 10.60/yr; adjusted hazard ratio [aHR] 1.104, 95% confidence interval [CI] 1.052–1.158, p < 0.001). For patients with ECAS, when compared to AP only, non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy was associated with lower risks for ischaemic stroke (aHR 0.551, 95% CI 0.454—0.669), the composite of ischaemic stroke/major bleeding (aHR 0.626, 95% CI 0.529—0.741) and the composite of ischaemic stroke/ICH (aHR 0.577, 95% CI 0.478—0.697), with non-significant difference for major bleeding and ICH. When compared to AP only, warfarin monotherapy was associated with higher risks of major bleeding (aHR 1.521, 95% CI 1.231—1.880), ICH (aHR 2.045, 95% CI 1.329—3.148), and the composite of ischaemic stroke and major bleeding. With combination of AP plus warfarin, there was an increase in ischaemic stroke, major bleeding, and the composite outcomes, when compared to AP only. NOAC monotherapy was the only approach associated with a positive NCB, while all other options (warfarin, combination of AP-OAC) were associated with negative NCB.ConclusionsFor post-stroke AF patients with ECAS, NOAC monotherapy was associated with lower risks of adverse outcomes and a positive NCB. Combination of AP with NOAC or warfarin did not offer any benefit, but more bleeding especially with AP-warfarin combination therapy.

Comparison of Outcomes in Patients Requiring Mechanical Circulatory Support Who Received Cangrelor in Addition to Anticoagulation Versus Anticoagulation Alone

ObjectivesTo evaluate the safety of cangrelor administered concurrently with heparin or bivalirudin in patients on mechanical circulatory support. DesignA single-center, retrospective, cohort study of adult patient consecutively admitted between January 2016 and October 2020 SettingA tertiary medical center. ParticipantsAdult patients admitted to the cardiovascular intensive care unit initiated on mechanical circulatory support for acute myocardial infarction (AMI) or non-AMI indications. Patients who received cangrelor underwent percutaneous coronary intervention with stenting during the index event or within the last year. InterventionsNone. Measurements and Main ResultsThe primary outcome was the incidence of major bleeding, defined by the Extracorporeal Life Support Organization criteria, in patients with mechanical circulatory support receiving cangrelor plus anticoagulation with heparin or bivalirudin with or without aspirin versus patients who did not receiving cangrelor. Sixty-eight patients were included in the study. Twenty-nine patients received cangrelor and 39 did not. Cangrelor was not associated with an increase in major bleeding, however our confidence interval was wide (adjusted hazard ratio [aHR] 1.93, 95% CI 0.61-6.11; p=0.262). ConclusionsPatients receiving cangrelor did not appear to be at higher risk of major bleeding compared to patients not receiving cangrelor. Larger trials should be conducted to better evaluate the safety of cangrelor in patients on mechanical circulatory support.

Prognostic Significance of Heart Failure in Acute Pulmonary Embolism: A Comprehensive Assessment of 30-Day Outcomes.

Patients with heart failure (HF) are known to have an increased risk of pulmonary embolism (PE), but there is limited evidence regarding the prognostic implications of HF in patients with acute PE and the relationship between PE prognosis and left ventricular ejection fraction (LVEF). The primary objective of this study was the development of a composite outcome (mortality, major bleeding, and recurrence) within the first 30 days. The secondary objective was to identify the role of LVEF in predicting the development of early complications in patients with both HF and reduced LVEF. A prospective study was conducted at two tertiary hospitals between January 2012 and December 2022 to assess differences among patients diagnosed with acute PE based on the presence or absence of a history of HF. Cox regression models were employed to assess the impact of HF and reduced LVEF on the composite outcome at 30 days. Out of 1991 patients with acute symptomatic PE, 7.13% had a history of HF. Patients with HF were older and had more comorbidities. The HF group exhibited higher mortality (11.27% vs. 4.33%, p < 0.001) and a higher incidence of major bleeding (9.86% vs. 4.54%, p = 0.005). In the multivariate analysis, HF was an independent risk factor for the development of the composite outcome (HR 1.93; 95% CI 1.35-2.76). Reduced LVEF was independently associated with a higher risk of major bleeding (HR 3.44; 95% CI 1.34-8.81). In patients with acute pulmonary embolism, heart failure is independently associated with a higher risk of early complications. Additionally, heart failure with reduced LVEF is an independent risk factor for major bleeding.

Comparison of ticagrelor and clopidogrel in anemic patients with acute coronary syndrome: efficacy and safety outcomes over one year.

This retrospective study aimed to investigate the potential impact of ticagrelor and clopidogrel treatment on cardiovascular outcomes in patients with anemia and acute coronary syndrome (ACS) and to provide insights into the optimal therapeutic approach for this vulnerable patient population. A retrospective research design was employed, involving patients diagnosed with ST-segment elevation myocardial infarction (STEMI) or non-ST-segment elevation myocardial infarction (NSTEMI) between 2014 and 2021. Inclusion criteria required a hemoglobin level below 12mg/dL and a minimum 12-month P2Y12 inhibitor treatment. Comprehensive clinical, biochemical, and echocardiographic data were collected from the hospital's electronic repository. The primary efficacy endpoint was major adverse cardiovascular events (MACE), encompassing total mortality, cardiovascular mortality, reinfarction, ischemic stroke, and hemorrhagic stroke. Major hemorrhage was the primary safety endpoint. Secondary outcomes included total mortality, cardiovascular mortality, reinfarction, ischemic stroke, and hemorrhagic stroke, individually. Patients treated with ticagrelor (n = 118) and clopidogrel (n = 538) were compared. No significant difference was observed in major adverse cardiovascular events (MACE) and major bleeding between ticagrelor and clopidogrel treatment groups (MACE: clopidogrel 10.0% vs. ticagrelor 11.0%, p = 0.75; major bleeding: clopidogrel 2.8%, ticagrelor 2.5%, p = 0.88). Patients with hemoglobin levels ≤ 8mg/dL demonstrated significantly higher MACE and major bleeding rates in the ticagrelor group (p = 0.008 and p = 0.002, respectively). Among patients aged ≥ 75 years, ticagrelor treatment was associated with a higher risk of major bleeding (p = 0.04). Ticagrelor and clopidogrel exhibited comparable efficacy and safety outcomes in anemic ACS patients over a one-year period. Although ticagrelor demonstrated superiority in reducing ischemic events, it is crucial to recognize the limitations of retrospective studies in informing clinical practice. This study offers valuable insights into tailoring antiplatelet therapy for anemic ACS patients and provides guidance for personalized treatment strategies, acknowledging the hypothesis-generating nature of retrospective analyses.

Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis.

Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations. Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI. Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83-1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09-3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83-1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments. According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Aspirin for the Primary Prevention of Cardiovascular Diseases in Patients with Chronic Kidney Disease: An Updated Meta-analysis.

Chronic kidney disease is associated with increased risk of cardiovascular diseases (CVD). This meta-analysis aims to evaluate the efficacy and safety of aspirin administered for primary prevention of CVD in patients with chronic kidney disease. PubMed, Scopus, Web of Science, CENTRAL and Clinicaltrials.gov were systematically searched from inception to 22 June 2023. Randomized controlled trials (RCTs) and cohort studies evaluating aspirin as primary prevention of CVD in chronic kidney disease were included. Meta-analysis was conducted using random-effects models. Overall, 11 studies (6 RCTs and 5 cohort studies) with 24,352 patients were included. The meta-analysis of RCTs indicated that aspirin was associated with lower risk of major adverse cardiovascular events [hazard ratio (HR): 0.79; 95% confidence intervals (CI): 0.64-0.97] and higher risk of major bleeding [risk ratio (RR): 1.35; 95% CI 1.15-1.58]. Incorporating observational evidence led to statistically non-significant findings in terms of risk of both cardiovascular events (pooled HR: 0.97; 95% CI 0.75-1.25; low certainty) and major bleeding (pooled RR: 1.21; 95% CI 0.99-1.48; moderate certainty). No statistically significant differences between aspirin and placebo were observed in the outcomes of mortality, coronary heart disease, stroke and renal events. RCT evidence points to a possible benefit in cardiovascular event reduction from aspirin administration, at the cost of increased major bleeding risk. This finding was not confirmed when the existing observational evidence was incorporated. Further research should determine the most appropriate subpopulation of chronic kidney disease patients that would benefit the most from prophylactic aspirin therapy. The study protocol has been prospectively registered and is publicly available from: https://doi.org/10.17504/protocols.io.261ged63jv47/v1 .

Dual Antiplatelet Therapy (DAPT) Versus Single Antiplatelet Therapy (SAPT) in Patients with Stroke Under 12 Hours: Meta-analysis and Systematic Review

Background: Patients with ischemic stroke under 12 hours are typically treated with antiplatelet therapy. Combining two antiplatelet medicines agents with differing actions and antithrombotic efficacy increases the risk of hemorrhage. Among 1000 patients with ischemic stroke, dual-antiplatelet therapy was associated with 1 to 7 more ICH events than clopidogrel monotherapy and seemed to provide no significant additional benefit in reducing ischemic stroke events. Method: Search in PubMed, EMBASE, and the Cochrane Central Register about dual antiplatelet therapy versus monotherapy. The research method used was PRISMA guidelines followed by literature exclusions. The inclusion criteria in this literature search were medicinal, literature from 2013-2023. Results: There is 5 literatures discussing the advantages of DAPT with the results obtained DAPT was not associated with a significant reduction in recurrent ischemic stroke [pooled RR 0.79 (95%CI 0.67-0.92)] but was associated with a higher risk of major bleeding [pooled RR 1.86 (95%IC 1.86-3.32)]. Conclusion: Immediate administration of DAPT &lt;12 hours after ischemic stroke can reduce recurrent stroke compared with antiplatelet monotherapy despite the increased risk of hemorrhage.

Longer‐Term Outcomes of the Yacoub versus Bentall Procedure in a Nationwide Propensity‐Matched Comparison

Background. Aortic root replacement with a composite mechanical valve graft (Bentall procedure) has been a recommended strategy in patients with aortic root aneurysm with or without aortic regurgitation. Aortic root remodeling (Yacoub procedure) has emerged as a valve‐sparing alternative although there is only scarce multicenter evidence. The aim of our study was to provide nationwide comparison of these two strategies. Methods. This was a retrospective study of data from national registry of cardiac surgery. Using propensity‐score matching, we compared all the patients undergoing the Bentall procedure in the Czech Republic between 2010 and 2021 with patients after the Yacoub procedure from four experienced centers. Results. During the study period, 199 patients underwent Yacoub and 526 had Bentall procedure. Of those, 166 pairs were selected and compared. There was no significant difference in perioperative outcomes and in mortality (p = 0.96) over the follow‐up of 5.7 vs. 6.4 years. The Bentall procedure was associated with a higher risk of major bleeding or thromboembolism (p &lt; 0.001), and the Yacoub procedure led to a higher risk of rehospitalizations for valve failure (p = 0.01). Conclusions. In a nationwide propensity‐matched study, Bentall and Yacoub procedures yield similar longer‐term survival. Yacoub offers better freedom from thromboembolism or bleeding at the cost of higher risk of valve failure.

Dual-Frequency Ultrasound Assisted Thrombolysis in Interventional Therapy of Deep Vein Thrombosis.

Deep vein thrombosis (DVT) is one of the main causes of disability and death worldwide. Currently, the treatment of DVT still needs a long time and faces a high risk of major bleeding. It is necessary to find a rapid and safe method for the therapy of DVT. Here, a dual-frequency ultrasound assisted thrombolysis (DF-UAT) is reported for the interventional treatment of DVT. A series of piezoelectric elements are placed in an interventional catheter to emit ultrasound waves with two independent frequencies in turn. The low-frequency ultrasound drives the drug-loaded droplets into the thrombus, while the high-frequency ultrasound causes the cavitation of the droplets in the thrombus. With the joint effect of the enhanced drug diffusion and the cavitation under the dual-frequency ultrasound, the thrombolytic efficacy can be improved. In a proof-of-concept experiment performed with living sheep, the recanalization of the iliac vein is realized in 15min using the DF-UAT technology. Therefore, the DF-UAT can be one of the most promising methods in the interventional treatment of DVT.

Efficacy of Direct Oral Anticoagulants Vs Warfarin Vs Low Molecular Weight Heparin in the Treatment of Acute Splanchnic Vein Thrombosis in Patients with Underlying Myeloproliferative Disorder

Introduction: Myeloproliferative neoplasms (MPNs) are hematopoietic stem cell disorders characterized by clonal proliferation of myeloid-lineage cells. Venous thrombosis poses a significant morbidity risk for MPN patients. The current recommended treatments for acute splanchnic vein thrombosis (SVT) are warfarin and low molecular weight heparin (LMWH). Direct oral anticoagulants (DOACs) are potential alternatives due to their predictable dose response and oral administration, but limited data exists for their use in acute SVTs. This retrospective study aims to assess the efficacy and outcomes of DOACs, LMWH, and warfarin in treating acute SVTs in patients with underlying MPN. Methods: We included patients of all ages with underlying myeloproliferative neoplasms and splanchnic vein thrombosis, with no underlying liver diseases, from Henry Ford Hospital Clinics in metropolitan Detroit, Michigan between 2013 and 2023. Patient data, which included age, gender, race, and BMI were recorded. The primary outcome was complete radiographic resolution (CRR) of the SVT, and secondary outcomes included recanalization, thrombosis progression, recurrent thrombosis, major bleeding, thrombocytopenia, and skin necrosis. The outcomes were compared between the three anticoagulant groups and patients using aspirin. Results: Among the 34 MPN patients with SVT, warfarin was prescribed most frequently (n=19), followed by enoxaparin (n=5) and DOACs (n=5). Although no significant differences were observed, warfarin showed the highest CRR rates (41.2%), while enoxaparin and DOACs had equal CRR rates (25%). DOACs showed recanalization rates similar to warfarin and higher than enoxaparin (44.4% and 47.1% vs. 20.0%, respectively). LMWH was associated with increased recurrent thrombosis rates (50.0%), while DOACs had a higher risk of major bleeding. All three anticoagulants had similar effects on thrombocytopenia and SVT progression. Aspirin use was linked to a higher risk of major bleeding (42.9%), but not using aspirin correlated with complete SVT resolution (30.8%), SVT progression (20.8%), recurrent thrombosis (29.2%), and thrombocytopenia (28.6%). Conclusions: Although limited by a small sample size, our study found no significant differences among the three anticoagulant groups. This contributes to establishing the role of DOACs in treating SVTs in patients with underlying MPN. Further studies with larger sample sizes are needed to explore the efficacy of DOACs compared to warfarin. Additionally, investigating the potential benefits of early thrombolysis in conjunction with anticoagulation for SVT patients with underlying MPN should be pursued, as the rates of complete resolution in these patients were low.

Safety and efficacy of direct oral anticoagulants in stroke prevention in patients with atrial fibrillation complicated with anemia and/or thrombocytopenia: a retrospective cohort study

BackgroundThere are limited data about the clinical benefits and harm of direct oral anticoagulants (DOACs) in stroke prevention in patients with atrial fibrillation (AF) complicated with anemia or thrombocytopenia.MethodsThis is a multi-center retrospective cohort study involving 5469 AF patients from 15 hospitals in China. Patients were divided into three groups according to hemoglobin and platelet levels: Group 1 (hemoglobin male ≥ 130 g/L; female ≥ 120 g/L and platelet ≥ 100 × 109/L), Group 2 (hemoglobin male < 130 g/L; female < 120 g/L or platelet < 100 × 109/L), and Group 3 (hemoglobin male < 130 g/L; female < 120 g/L and platelet < 100 × 109/L). Patients in each category are further divided into two groups according to their stroke prevention strategies: rivaroxaban or dabigatran. Clinical results include major, minor, total bleeding, thrombosis, and the composite outcome of major bleeding and thrombosis.ResultsHigher hemoglobin levels were associated with a reduced risk of total bleeding and major bleeding, while platelet counts were not associated with any event. Compared with Group 1, Group 2 had a higher risk of major bleeding (aOR 1.70, 95%CI 1.12–2.57, P = 0.012), and the composite endpoint of major bleeding and thrombosis (aOR 1.70, 95%CI 1.19–2.44, P = 0.004). Compared with Group 1, Group 3 had a higher total bleeding risk (aOR 2.15, 95%CI 1.14–4.05, P = 0.018). Compared with dabigatran, rivaroxaban was associated with higher composite risk in Group 1 (aOR 2.91, 95% CI 1.66–5.16, P < 0.001) and Group 2 (aOR 3.05, 95%CI 1.46–6.39, P = 0.003), but there was no significant difference in Group 3 (aOR 1.78, 95%CI 0.23—13.54, P = 0.577).ConclusionsHigher hemoglobin levels are associated with a reduced risk of total bleeding and major bleeding in patients with AF. Dabigatran was associated with better clinical outcomes than rivaroxaban in patients with anemia or thrombocytopenia but not in those with anemia and thrombocytopenia.

Clinical Outcomes in Patients With Atrial Fibrillation Treated With Non-Vitamin K Oral Anticoagulants Across Varying Body Mass Index.

There are conflicting data on outcomes in patients with atrial fibrillation treated with non-vitamin K oral anticoagulants across varying body mass index (BMI). We investigated cardiovascular and bleeding risk in patients with atrial fibrillation with varying BMI. Observational cohort study from the Swedish oral anticoagulation registry between August 2, 2011, and December 31, 2018. Primary outcomes were mortality, ischemic stroke/systemic embolism, and major bleeding. Baseline BMI (kg/m2) was analyzed continuously and categorized: underweight (<18.5 kg/m2), normal weight (18.5 to <25 kg/m2), preobesity (25 to <30 kg/m2), and obesity class I to III (30 to <35, 35 to <40, and ≥40 kg/m2). Adjusted Cox models and nonlinear relationships of BMI were modeled using restricted cubic splines. Non-vitamin K oral anticoagulant-treated patients with atrial fibrillation were included (n=26 047). At baseline, 602 (2.3%) were underweight, 9101 (34.9%) were normal weight, 9970 (38.3%) were preobese, 4280 (16.4%) were obese class I, 1486 (5.7%) were obese class II, and 608 (2.3%) were obese class III. Underweight and obesity class III were in adjusted continuous analysis associated with increased mortality and major bleeding, with lowest risk observed among preobese patients with BMI 28.2 and 26.2 kg/m2, respectively. In adjusted categorical analysis, underweight was associated with increased mortality (hazard ratio [HR], 1.77 [95% CI, 1.57-1.99]) and nonsignificant higher risk of major bleeding (HR, 1.23 [95% CI, 0.95-1.58]). Similarly, obesity class III was associated with increased mortality (HR, 1.67 [95% CI, 1.40-1.99]) and major bleeding (HR, 1.68 [95% CI, 1.29-2.17]). No significant association was observed between higher BMI and ischemic stroke/systemic embolism. In non-vitamin K oral anticoagulant-treated patients with atrial fibrillation, there appears to be a U-shaped relationship between BMI and mortality and major bleeding.

The impact of ticagrelor therapy on CABG-related bleeding in patients with STEMI managed with pPCI

Abstract Background Patients on double antiplatelet treatment who need early in-hospital coronary artery bypass grafting (CABG) are at high risk of major bleeding. However, recent studies have demonstrated that early CABG surgery within 7 days of discontinuation of p2Y12 inhibitors are safe with respect to bleeding events in patients with acute coronary syndrome. Purpose In this study, we aimed to investigate the impact of ticagrelor preloading on CABG related bleeding in patients with ST-segment elevation myocardial infarction (STEMI) initially managed with primary percutaneous coronary intervention (pPCI). Methods Patients with the diagnosis of STEMI who were managed with pPCI and underwent subsequent early (4-7 days following pPCI) or delayed (&amp;gt; 7 days following pPCI) CABG surgery were included. All study patients were preloaded with ticagrelor 180 mg prior to pPCI procedure. Patients’ demographics, clinical variables and short-term cardiovascular outcomes were recorded. Results The study cohort included 98 patients. Fifty-four (54%) patients underwent early and 44(45%) patients underwent delayed CABG surgery. Left main coronary artery involvement and presence of chronic total occlusion in the non-infarct related artery were 26.5% and 25.5%. CABG-related bleeding occurred in 22 (22.4%) patients. There was no significant difference with respect to total ticagrelor dose and timing of the surgery between patients with or without CABG-related bleeding (p: 0.165 and p:0.142). Multivariate analyses demonstrated that only preoperative hemoglobin level was an independent predictor of CABG-related bleeding (OR:0.720, p: 0.034).There were three deaths within the 30 days of surgery, all occurring in patients with CABG-related bleeding. However, CABG-related bleeding was not associated with long-term cardiovascular events during the follow-up. Conclusion Our results indicated that discontinuation of ticagrelor therapy 3 days prior to surgery is sufficient to avoid CABG-related bleeding. Moreover, early CABG following STEMI does not increase the risk of long-term cardiovascular events.

Bleeding risk profile and heart failure hospitalizations in patients with atrial fibrillation according to FIB-4 index

Abstract Introduction Fibrosis-4 index (FIB-4 index), calculated by age, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and platelet count, is a simple marker to evaluate liver fibrosis. The FIB-4 index is associated with higher all-cause mortality in patients with heart failure (HF). However, the relationship between liver stiffness and atrial fibrillation remains unclear. Purpose The present study explores the impact of the FIB-4 index in the bleeding risk and heart failure hospitalizations among a large cohort of AF patients. Methods The Fibrosis-4 index (FIB-4) was applied to 10,530 patients diagnosed with AF from our health area between January 2014 and April 2020. Patients were analyzed in three regions of the Fib-4index based on the cutoff points (Group 1 F0&amp;lt;1.30, group 2 F1-F2:1.30–2.67 and group 3 F3-F4: &amp;gt;2.67). The outcome was a composite of major bleeding events and hospitalization for heart failure. The risk of the combined end-point was determined by competing risk regression. Results 4471 patients (42.5 %) were included in Group 1, 5139 (48.8 %) in Group 2 and 920 (7.4%) in Group 3. During a mean follow-up of 3.78±2.05 years, 1,834 patients died (17.49%), 2,359 had a heart failure hospitalization (22,42%) and 772 had a major bleeding (7.36%). The incidence of major bleeding and heart failure hospitalizations was significantly higher amongst group 3. In the univariate analysis, group 2 and group 3 were associated with increased risk of the combined outcome (Figure 1). Multivariate adjustment was developed including all those variables with clinical significance and those that had been associated in the univariate analysis. Group 3 was associated with higher increased risk of major bleeding and heart failure hospitalizations (sHR 1.21, 95% CI 1.05-1.39; P=0.007), whilst Group 2 not (1.06, 95% CI 0.97-1.16; P=0.169) in comparison with Group 1. Conclusions FIB4 index &amp;gt;2.67 was associated with higher risk of major bleeding and heart failure hospitalizations. FIB-4 index may reflect venous congestion and it could be an useful tool for predicting HF and major bleeding events in patients with AF.Figure 1

Safety and healthcare resource utilisation in patients undergoing left-atrial appendage closure - A nationwide analysis

Abstract Background Percutaneous left-atrial appendage closure (LAAC) has emerged as a non-pharmacological alternative for stroke prevention in patients with atrial fibrillation (AF) not suitable for anticoagulation therapy. Real-world data on peri-procedural outcomes are limited. Purpose To analyse outcomes of peri-procedural in-hospital safety and healthcare resource utilisation after percutaneous LAAC. Methods The US National Inpatient Sample was utilised to identify AF patients undergoing LAAC from 2016 to 2019. Primary outcomes (safety) were in-hospital stroke or systemic embolism (SE), pericardial effusion (PE), major bleeding, device embolisation and mortality. Secondary outcomes (resource utilisation) were adverse discharge disposition, hospital length of stay (LOS) and treatment costs. Logistic and Poisson regression models were used to analye outcomes by adjusting for 10 confounders. Results 11,240 adult patients (with 41.9% being female) with AF undergoing LAAC were included. SE decreased by 97% between 2016 and 2019 [95% Confidence Interval (CI) 0-0.24] (P=0.003), while a trend to lower numbers of other peri-procedural complications was determined. In-hospital mortality remained stable (0.14%). Hospital LOS decreased by 18% (0.78-0.87, P&amp;lt;0.001) and adverse discharge rate by 41% (95% CI 0.41-0.86, P=0.005) between 2016 and 2019, while hospital costs did not significantly change (P=0.2). Of note, female patients had a higher risk of PE (OR 2.86 [95% CI 2.41-6.39]) and SE (OR 5.0 [95% CI 1.28-43.6]), while patients with multiple comorbidities had higher risks of major bleeding (P&amp;lt;0.001), mortality (P=0.031), longer hospital LOS (P&amp;lt;0.001) and increased treatment costs (P=0.073). Male patients had the most peculiar decrease in adverse discharge rate between 2016 and 2019: OR 0.45 [95% CI 0.27-0.77]. Significant differences in all outcomes were observed between male and female patients across US regions (Figure). Subgroup analyses confirmed that female patients had a prolonged LOS and higher risk of adverse discharge disposition than male patients. Conclusions LAAC has become a safer and more efficient procedure. Significant sex differences existed across US regions. Careful considerations should be taken when performing LAAC in female and comorbid patients.