High Risk Of Bleeding Research Articles

Cancer complicated by thrombosis and thrombocytopenia: still a therapeutic dilemma

Individuals who have thrombocytopenia and cancer-associated thrombosis (CAT) are difficult to manage because they have a high risk of bleeding and recurrent thrombosis. The International Society on Thrombosis and Haemostasis guidelines for the management of thrombocytopenia in patients with CAT suggest two main approaches: either complete anticoagulation with transfusion support if necessary, or dose-modified anticoagulation while the platelet count is <50×109/L. Nevertheless, rather than being based on information from randomized controlled trials (RCTs), these recommendations were based on expert consensus. Recent research from two different countries has shown how this cohort’s management and results vary widely. While the United Kingdom study, Cancer-Associated Venous Thrombosis and Thrombocytopenia, found no significant differences in bleeding or recurrent thrombosis between full dose and modified dose groups, the North American Thrombocytopenia Related Outcomes with Venous thromboembolism study demonstrated a significantly lower risk of bleeding events in those receiving modified dose anticoagulation compared to full dose, without an increased risk of recurrent VTE. Therefore, an RCT is required to assess the best course of action for patients with CAT and thrombocytopenia. To define the standard of care for the management of patients with CAT and thrombocytopenia, a full-scale trial called the START randomized trial (STrategies for Anticoagulation in patients with thRombocytopenia and cancer-associated Thrombosis) is an international, multi-site pilot study that compares the use of platelet transfusions plus higher dose anticoagulation to modified dose anticoagulation in patients with thrombocytopenia and CAT receiving anticoagulation.

SAFETY AND EFFICACY OF A LIGHT ANTITHROMBOTIC REGIMEN AFTER LEFT ATRIAL APPENDAGE OCCLUSION: INSIGHTS FROM THE LOGIC (LEFT ATRIAL APPENDAGE OCCLUSION IN PATIENTS WITH GASTROINTESTINAL OR INTRACRANIAL BLEEDING) INTERNATIONAL MULTICENTER REGISTRY

Abstract Background Antithrombotic therapy (AT) after left atrial appendage occlusion (LAAO) in patients with non–valvular atrial fibrillation (NVAF) has the purpose of preventing device related thrombosis (DRT), avoiding embolic events; nevertheless, the correct antithrombotic regimen after LAAO is still under debate. Aims Aim of this substudy of the observational LOGIC registry was to describe the efficacy and safety of a light antithrombotic regimen, comprising single antiplatelet therapy or none, compared to a standard antithrombotic regimen, after a successful LAAO. Methods Patients with NVAF that underwent LAAO were previously included in the LOGIC registry. Patients receiving single or no AT were considered as light therapy group, while other regimen were considered as standard regimen group. Outcomes of interest were: death from any causes and cardiovascular death, ischemic stroke, transient ischemic attack and systemic embolization, any bleeding and major bleeding at 12 months. Results. Six hundred and twenty–eight patients were considered in the analysis, 31.4% received a light antithrombotic regimen. There were no differences in overall and cardiovascular mortality (5.1% Vs 6.7%, p=0.426 and 2.0% Vs 1.4%, p=0.553 respectively). Cerebrovascular stroke and transient ischemic attack were similar between the two groups (1.5% Vs 1.4%, p=0.898 and 1.5% Vs 1.3%, p=0.847). Light regimen was not associated with an increased rate of systemic embolism (1.0% Vs 0.7%, p=0.447 and HR 0.88 [95% CI: 0.34 – 2.27; p=0.79]). Conclusions An AT regimen based on single or no antithrombotic therapy after LAAO seems to be safe in patients with high–bleeding risk, without increasing cerebrovascular or peripheral ischemic events.

BETWEEN SCYLLA AND CHARYBDIS: MULTIPLE LEFT ATRIAL THROMBI DESPITE ORAL ANTICOAGULATION AND ANTIPLATELET THERAPY IN A PATIENT CANDIDATE FOR LEFT ATRIAL APPENDAGE OCCLUSION

Abstract Introduction Left atrial (LA) thrombosis usually occurs in patients affected by atrial fibrillation (AF), generally involving the left atrial appendage (LAA). We present the unexpected echocardiographic finding of multiple LA thrombi despite an adequate antithrombotic strategy. Case Presentation A 76–year–old lady underwent transesophageal echocardiographic examination (TOE) to assess eligibility for percutaneous LAA occlusion (LAAO) procedure due to high bleeding risk. Her medical history included AF and a recent percutaneous coronary revascularization; therefore, her antithrombotic therapy included apixaban 2.5 mg bid and clopidogrel 75 mg od. The TOE showed LA structural and functional remodeling with spontaneous echo contrast and multiple thrombi involving the LAA (one [12 x 9 mm] overflowing the orifice and attached to the Coumadin Ridge and the second [12 x 7 mm] attached and arising from the tunnel of patent foramen ovale). Mitral valve stenosis was excluded (Fig.1). Due to TOE findings, the patient was not considered eligible for percutaneous LAAO. Due to the concomitant very high thromboembolic risk, despite the previous intracranial bleeding, we decided to stop apixaban and to start parenteral anticoagulation for 3 weeks with low–molecular weight heparin (100 UI/kg bid) followed by the switch to a vitamin k antagonist (VKA). We also prescribed a hematological evaluation to exclude a hypercoagulability disorder. Our patient’s daughter was a carrier of a mutation in both the methylenetetrahydrofolatereductase and Thrombin genes. A TOE after 30 days showed the persistence of LA thrombi, although with significantly reduced size and mobility (Fig.2). The follow–up was clinically uneventful. We suggested to continue anticoagulation therapy with VKA, and we planned a new TOE after 4 weeks. Discussion Although proper anticoagulation decreases cardioembolic risk in patients with AF, atrial thrombosis may occur due to LA remodeling, high CHA2DS2–VASc score and other factors, including hypercoagulability disorders. The presence of multiple LA thrombi represents a challenge for clinicians, especially in case of concomitant high thromboembolic and bleeding risk. However, the best treatment strategies for these extreme conditions are not defined, so far. Therefore, the therapeutic choice is often tailored to the single patient and based on the clinical judgment, bearing in mind that avoiding Charybdis means passing to close to Scylla and vice versa.

PERCUTANEOUS CORONARY INTERVENTIONS IN PATIENTS TREATED WITH ORAL ANTICOAGULANT THERAPY: BASELINE CLINICAL CHARACTERISTICS OF THE PERSEO REGISTRY

Abstract Background International guidelines recommend a dual antithrombotic therapy (DAT) with direct oral anticoagulant (DOAC) for patients on chronic oral anticoagulant therapy (OAT) undergoing percutaneous coronary intervention with stent implantation (PCI–S). However, the implementation of practice Guidelines in the “real world” is often a complex exercise. Aim of the multicenter prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) registry was to evaluate the management of the different antithrombotic regimens strategies in patients with an indication for OAT undergoing PCI–S in a “real world” setting and its association with clinical outcomes. Methods The PERSEO registry has been designed to enrol patients requiring OAT and treated by PCI–S in 25 Italian Cardiology Centres. No exclusion criteria have been defined. The primary end–point was a combined measure of efficacy and safety outcome (NACE), including major bleeding events + major adverse cardiac and cerebral events at one year follow up in patients treated with DOAC compared to vitamin K antagonists. Results From February 2018 to February 2022, a total of 1233 patients were enrolled: mean age 74±9 years, 900 males and 333 females. The primary indication for OAT was atrial fibrillation (1066 patients, 87%) while an acute coronary syndrome was the leading reason for PCI–S (789 patients, 64%). Of those, 271 patients had an ST elevation myocardial infarction at admission. Mean CHA2DVAS2C score and HASBLED score were respectively 4±2 and 4±1. Six patients died during hospitalization and 1227 were discharged alive: 1027 on triple antithrombotic therapy (oral anticoagulant and dual antiplatelet therapy), 196 patients on DAT (oral anticoagulant and single antiplatelet therapy) and 4 patients on oral anticoagulant alone. The majority of patients enrolled were discharged on DOAC (1006 patients, 82%), whereas only a minority received vitamin K antagonists (221 patients, 18%). Conclusions The Italian PERSEO Registry is the largest prospective observational study comparing different antithrombotic strategies in patients with an indication for OAT undergoing PCI–S in a “real world” setting. Baseline characteristics, depicted a population at high thrombotic and haemorrhagic risk. In agreement with current guidelines the majority of patients were discharged on DOAC, yet the use of a DAT was still limited to a minority of the patients included.

THE GLA D313Y MUTATION IN FABRY DISEASE: DIAGNOSTIC DILEMMAS AND THERAPEUTIC CONSIDERATIONS

Abstract Fabry disease is a genetic disorder caused by mutations in the GLA gene, which encodes alpha–galactosidase A, leading to enzyme dysfunction and subsequent accumulation of glycosphingolipids. In the classical form, it occurs in childhood or early adolescence with renal, cardiac, and neurological involvement, resulting in a poor prognosis. The GLA D313Y is a missense mutation resulting in a significant reduction of enzyme activity in plasma, while leukocyte enzyme activity remains within normal limits, leading to a "pseudo–deficiency" of enzyme activity with uncertain pathogenicity. In literature, it has been observed that individuals with this mutation may present predominantly with central neurologic manifestations, characterized by multifocal white matter lesions. Historically they do not receive indications for initiating enzyme replacement or molecular chaperone therapies. We present the case of a man affected by arterial hypertension and history of chronic lower limb pain who experienced a lacunar stroke at the age of 35. The GLA D313Y mutation was identified and enzyme activity assay in plasma was within normal limits, precluding the initiation of enzyme replacement therapy. Over the following years, he suffered two additional ischemic strokes, a progressive decline in renal function to stage 3, and acute coronary syndrome. Transthoracic echocardiography revealed hypertrophic non–obstructive cardiomyopathy (SIVd 20 mm) with normal biventricular ejection fraction. Cardiac magnetic resonance showed late gadolinium enhancement of inferior junctional and inferior wall in middle segment (Fig.1). Considering the patient‘s clinical conditions involving multi–organ impairment, an enzymatic activity test was performed on leukocytes, revealing a reduced activity. This prompted the decision to initiate enzyme replacement therapy. This case report supports the hypothesis that the D313Y mutation may be associated with a later presentation and not only neurological involvement. In our experience, it’s mandatory to proceed with the determination of leukocyte enzyme activity in presence of normal enzyme activity in plasma. As an alternative, the detection of glycosphingolipids’ accumulation could be useful, but myocardial and renal biopsy poses a high bleeding risk, especially in anticoagulated or antiaggregated patients. The authors propose considering the initiation of therapy in patients with the D313Y mutation who exhibit significant organ involvement.

Individualising Antithrombotic Strategies for Acute and Chronic Coronary Syndromes.

For patients presenting with acute or chronic coronary syndromes, current guideline recommendations and expert consensus provide a range of options for antithrombotic treatment. The European Society of Cardiology 2023 guidelines on the management of acute coronary syndrome emphasise the need to assess the risk of both ischaemic events and bleeding. Those with high bleeding risk warrant particular consideration of the duration and intensity of antithrombotic therapy combinations. A joint consensus of experts takes a similar approach, informed by two network meta-analyses that appraised all available antithrombotic treatments within or after the 12 months following coronary revascularisation and/or acute coronary syndrome and individual participant data from six trials. In this article, four case studies are used to illustrate how these guidelines and expert consensus recommendations can be applied in clinical practice.

Feasibility, safety, and efficacy of endovascular treatment of anterior cranial fossa dural arteriovenous fistulas: a systematic review and meta-analysis with a subanalysis for Onyx.

Dural Arteriovenous Fistulas (dAVFs) of the anterior cranial fossa (ACF) are uncommon but carry a high risk of hemorrhage and pose substantial treatment challenges. Recent advancements in endovascular treatment (EVT), including the introduction of novel liquid embolic agents, have markedly bolstered EVT's role in managing ACF-dAVFs, with notable series published in the last five years. We aimed to assess the feasibility, safety, and efficacy of EVT for ACF-dAVFs. We searched Medline, Scopus, Web of Science, and Cochrane Library databases following PRISMA guidelines. Eligible studies included those with ≥ 5 patients undergoing embolization of ACF-dAVFs, detailing both angiographic and clinical outcomes. We used single proportion analysis with 95% confidence intervals under a random-effects model, I2 to assess heterogeneity, and Baujat and sensitivity analysis to address high heterogeneity. Publication bias was assessed by funnel-plot analysis and Egger's test. Outcomes included complete occlusion following embolization, unsuccessful endovascular embolization attempts, incomplete occlusion following embolization, symptom resolution or clinical improvement following embolization, recurrence; procedure-related complications, morbidity, and mortality. Additionally, a subanalysis for studies exclusively utilizing Onyx™ embolic system was done. Eighteen studies comprising 231 ACF-dAVF were included. Unsuccessful endovascular embolization attempts rate was 2%. Complete occlusion rate was 85%, with 4% of complications. Incomplete occlusion rate was 10%. Successfully embolized patients experienced either symptom resolution or clinical improvement in 94% of cases. Morbidity and mortality rates were 1% and 0%, respectively. Onyx subanalyses showed an overall rate of 0% for unsuccessful attempts, 95% for complete occlusion, and 5% for incomplete occlusion. Symptom resolution or clinical improvement was 98% and recurrence rate was 0%. EVT for ACF-dAVF is highly feasible, effective, and safe, with a low rate of complications, morbidity, and mortality. The subanalyses focusing on Onyx embolizations revealed superior efficacy and safety outcomes compared to the findings of the primary analyses involving all included studies.

Is low-dose anticoagulation a therapeutic option for patients at high risk of bleeding with high-risk pulmonary thromboembolism

This issue of Chinese Journal of Tuberculosis and Respiratory Diseases published an interesting case illustrating the identification, treatment, and post-treatment management of a high-risk pulmonary thromboembolism (PTE) that occurred during surgery. It was a high-risk case of PTE, but during treatment, the risk stratification changed to medium-high risk. We should dynamically assess risk stratification and develop diagnosis and treatment plans based on changes in the patient's condition. At the same time, there was a high risk of bleeding in this patient. We should try to decrease the risk of bleeding as much as possible, consider all the conditions that can be applied at that time and on a local level, and devise a safe and effective treatment plan. The socio-economic status of patients may have an impact on how the final diagnosis and treatment plan are implemented. We need to communicate fully with patients, consider comprehensively, and prepare contingency plans to ensure patients' life safety to the greatest extent possible.

Comparison of rivaroxaban and low molecular weight heparin in the treatment of cancer-associated venous thromboembolism: a Swedish national population-based register study

BackgroundTreating cancer-associated venous thromboembolism (CAT) with anticoagulation prevents recurrent venous thromboembolism (rVTE), but increases bleeding risk.ObjectivesTo compare incidence of rVTE, major bleeding, and all-cause mortality for rivaroxaban versus low molecular weight heparin (LMWH) in patients with CAT.MethodsWe developed a cohort study using Swedish national registers 2013–2019. Patients with CAT (venous thromboembolism within 6 months of cancer diagnosis) were included. Those with other indications or with high bleeding risk cancers were excluded (according to guidelines). Follow-up was from index-CAT until outcome, death, emigration, or end of study. Incidence rates (IR) per 1000 person-years with 95% confidence interval (CI) and propensity score overlap-weighted hazard ratios (HRs) for rivaroxaban versus LMWH were estimated.ResultsWe included 283 patients on rivaroxaban and 5181 on LMWH. The IR for rVTE was 68.7 (95% CI 40.0–109.9) for rivaroxaban, compared with 91.6 (95% CI 81.9–102.0) for LMWH, with adjusted HR 0.77 (95% CI 0.43–1.35). The IR for major bleeding was 23.5 (95% CI 8.6–51.1) for rivaroxaban versus 49.2 (95% CI 42.3–56.9) for LMWH, with adjusted HR 0.62 (95% CI 0.26–1.49). The IR for all-cause mortality was 146.8 (95% CI 103.9–201.5) for rivaroxaban and 565.6 (95% CI 541.8–590.2) for LMWH with adjusted HR 0.48 (95% CI 0.34–0.67).ConclusionsRivaroxaban performed similarly to LMWH for patients with CAT for rVTE and major bleeding. An all-cause mortality benefit was observed for rivaroxaban which potentially may be attributed to residual confounding.Trial registration numberNCT05150938 (Registered 9 December 2021).

Nonsevere Hemophilia: The Need for a Renewed Focus and Improved Outcomes.

People with nonsevere hemophilia (PWNSH) are phenotypically more diverse than those with severe hemophilia. Perceptions relating to a "nonsevere" phenotype have contributed to fewer research initiatives, fewer guidelines on optimal management, and a lack of standards for surveillance and clinical assessment for affected individuals. In many cases, episodes of abnormal bleeding could, if investigated, have led to earlier diagnosis. Furthermore, the major recent developments in therapy for hemophilia have largely focused on severe disease and, as a group, PWNSH have not been included in many key clinical trials. Benefiting people with severe disease, innovative replacement therapies have generally targeted factor levels that are above those present in a large proportion of PWNSH. Therapeutic advances can lead to improvement in phenotype for people with severe hemophilia over that currently experienced by many PWNSH. As a result, we are approaching a point where PWNSH may, in many countries, have a higher risk of bleeding and restriction in lifestyle than those with severe disease but with more limited therapeutic options. Given the multiple major advances in treatment for people with hemophilia, it is timely to review the aspects of nonsevere disease, to ensure equity in care and management for all individuals with this condition.

Defining high bleeding risk in patients undergoing transcatheter aortic valve implantation: a VARC-HBR consensus document.

<span style="font-size:12pt"><span style="font-family:Aptos,sans-serif">The identification and management of patients at high bleeding risk (HBR) undergoing transcatheter aortic valve implantation (TAVI) are of major importance, but the lack of standardised definitions is challenging for trial design, data interpretation, and clinical decision-making. The Valve Academic Research Consortium for High Bleeding Risk (VARC-HBR) is a collaboration among leading research organisations, regulatory authorities, and physician-scientists from Europe, the USA, and Asia, with a major focus on TAVI-related bleeding. VARC-HBR is an initiative of the CERC (Cardiovascular European Research Center), aiming to develop a consensus definition of TAVI patients at HBR, based on a systematic review of the available evidence, to provide consistency for future clinical trials, clinical decision-making, and regulatory review. This document represents the first pragmatic approach to a consistent definition of HBR evaluating the safety and effectiveness of procedures, devices and drug regimens for patients undergoing TAVI.</span></span>.

Peripheral intravenous catheter failure, nurse staffing levels and care complexity individual factors: A retrospective multicentre cohort study

Introduction Short peripheral intravenous catheter (PIVC) failure is a common complication that is generally underdiagnosed. Some studies have evaluated the factors associated with these complications, but the impact of care complexity individual factors and nurse staffing levels on PIVC failure is still to be assessed. The aim of this study was to determine the incidence and risk factors of PIVC failure in the public hospital system of the Southern Barcelona Metropolitan Area. Methods A retrospective multicentre observational cohort study of hospitalised adult patients was conducted in two public hospitals in Barcelona from 1st January 2016 to 31st December 2017. All adult patients admitted to the hospitalisation ward were included until the day of discharge. Patients were classified according to presence or absence of PIVC failure. The main outcomes were nurse staffing coverage (ATIC patient classification system) and 27-care complexity individual factors. Data were obtained from electronic health records in 2022. Results Of the 44,661 patients with a PIVC, catheter failure was recorded in 2,624 (5.9%) patients (2,577 [5.8%] phlebitis and 55 [0.1%] extravasation). PIVC failure was more frequent in female patients (42%), admitted to medical wards, unscheduled admissions, longer catheter dwell time (median 7.3 vs 2.2 days) and those with lower levels of nurse staffing coverage (mean 60.2 vs 71.5). Multivariate logistic regression analysis revealed that the female gender, medical ward admission, catheter dwell time, haemodynamic instability, uncontrolled pain, communication disorders, a high risk of haemorrhage, mental impairments, and a lack of caregiver support were independent factors associated with PIVC failure. Moreover, higher nurse staffing were a protective factor against PIVC failure (AUC, 0.73; 95% confidence interval [CI]: 0.72–0.74). Conclusion About 6% of patients presented PIVC failure during hospitalisation. Several complexity factors were associated with PIVC failure and lower nurse staffing levels were identified in patients with PIVC failure. Institutions should consider that prior identification of care complexity individual factors and nurse staffing coverage could be associated with a reduced risk of PIVC failure.

Characteristics, management and prognosis of patients with coronary artery disease undergoing coronary intervention and atrial fibrillation

Abstract Funding Acknowledgements None. Introduction The selection of antithrombotic treatment in patients with ischaemic heart disease (IHD) and atrial fibrillation (AF) represents a challenge when trying to balance ischaemic and haemorrhagic risk. However, there is little "real-life" data on the selected antithrombotic treatment and its short and long-term prognosis. Methods A Prospective multicentre study that includes patients with IHD [acute coronary syndrome (ACS) or chronic coronary syndrome (CCS)] and AF admitted to 13 Spanish centres. The objective is to describe the characteristics, antithrombotic treatment and prognosis of patients undergoing PCI and AF. Results 373 patients were included. The average age was 77.6 ± 9.8 years (28% women). Patients had a high ischaemic and haemorrhagic risk [CHA2DS2VASc 4 (2-5) and HASBLED 3 (2-4)], with 25.5% being frail according to the Clinical Frailty Scale. The main reason for admission was ACS (44.8% NSTEMI, 22.2% STEMI and 33% CCS ), and 49.8% of patients had multivessel disease. 70.3% of patients underwent revascularisation, mainly percutaneously (92.2%). Among those percutaneously revascularised, the most used antithrombotic treatment was triple therapy with double antiplatelet therapy (DAPT) + oral anticoagulant (OAC) (62.5%), followed by double therapy with monoantiplatelet therapy + OAC (29.2%). In revascularised patients over 80, the most selected antithrombotic therapy was similar: 60.5% and 28.9%, respectively. The most used OAC was apixaban (42.3%), followed by vitamin K antagonists (17.3%). One-year survival was 88.5%. 2.6% of patients presented an ischemic stroke, and 4.8% suffered a new ACS. At the same time, haemorrhagic events (BARC ≥2) were 8.9%. Conclusions A high ischaemic and haemorrhagic risk co-exists in patients with IHD and AF. In our setting, triple therapy, mainly with the use of DOACs over VKA, is the preferred therapy. The long-term mortality of this subgroup of patients with IHD is high (&amp;gt;10%), with a rate of haemorrhagic events (8.9%) higher than ischaemic events (4.8%).Characteristics of patients

Clinical characteristics and atrial fibrillation management in hospitalized patients with heart failure with reduced versus preserved ejection fraction

Abstract Funding Acknowledgements None. Background Non-valvular atrial fibrillation (NVAF) and heart failure (HF) frequently coexist. AF management in HF is currently changing with increasing role of rhythm control. Data about clinical characteristics and AF management in hospitalized patients with HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF) are lacking. The purpose of the study was to assess the clinical characteristics and AF management in hospitalized patients with NVAF and HFrEF and compare them to those of NVAF and HFpEF. Methods Consecutive NVAF patients hospitalized with HF decompensation between January 2020 and May 2022 were retrospectively evaluated. Patients were divided into two groups: HFrEF and HFpEF (defined as left ventricular ejection fraction &amp;gt; 40%). Clinical characteristics and AF treatment strategy in both groups were studied and compared. Numerical data are expressed as median (interquartile range). P&amp;lt;0.05 was considered significant. Results In a total of 388 AF-HF patients (age 73.5 years [66-82], 59.3% males), 147 (37.9%) had reduced ejection fraction. Patients with HFrEF compared to those with HFpEF were younger (69.3 vs 74.7 years; P &amp;lt; 0.001), more often male and with a higher rate of NYHA classes III-IV (73.9% vs 63.5%; P &amp;lt; 0.05), N-terminal pro-B-type natriuretic peptide level (2658.5 pg/ml vs 1799.1 pg/ml; p&amp;lt;0.001), sum of B-lines by lung ultrasound (35.2 vs 28.9; P&amp;lt;0.05) and prevalence of non-paroxysmal forms of AF (70.4% vs 50.4%; p &amp;lt; 0.05). Patients with HFrEF had a higher burden of coronary artery disease, chronic kidney disease and prior stroke (31.7% vs 19.2%, 83.9% vs 69.0, 18.5% vs 9.7%, respectively; p&amp;lt; 0.05 for all) than HFpEF patients. Patients with HFpEF were more likely than those with HFrEF to have diabetes mellitus (25.9% vs 37.1%; p&amp;lt; 0.05) The subgroup of patients with HFrEF compared to those with HFpEF had higher bleeding risk (HAS-BLED ≥3 in 32.1% vs 20.4%, P&amp;lt;0.05) due to more frequent abnormal renal/liver function, concomitant antithrombotic treatment/alcohol, prior stroke (24.7% vs 10.6%, 28.4% vs 16.8%, 18.5% vs 9.7%, respectively; P&amp;lt;0.05 for all) but lower thromboembolic risk according to CHA 2 DS 2 -VASc (4.0 vs 4.4; p &amp;lt; 0.05). Oral anticoagulants (OAC) were administered in 88% of patients on discharge. Patterns of anticoagulation administration didn’t differ between the two groups. Patients with HFrEF were less likely to receive first-line rhythm control for AF compared to HFpEF patients (36.1% vs 68.1%; p&amp;lt;0.05). Conclusion Hospitalized patients with NVAF and HFrEF compared to those with HFpEF were younger, with greater severity of HF, higher burden of comorbidities and bleeding risk and slightly lower thromboembolic risk. Despite different clinical characteristics, OAC administration patterns were similar and OAC prescription rate was not optimal in both groups. There is a need for improvement of guideline adherence to first-line rhythm control strategy in AF and HFrEF.

P2Y12 monotherapy versus standard dual antiplatelet therapy after percutaneous coronary intervention: a systematic review and meta-analysis

Abstract Funding Acknowledgements None. Introduction Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 receptor inhibitor after percutaneous coronary intervention (PCI) is the recommended therapy for lowering the ischemic risk among patients with acute coronary syndrome (ACS). However, the increased incidence of bleeding is a major concern. Monotherapy with a P2Y12 inhibitor after short-term DAPT to reduce adverse cardiovascular events and bleeding rates has not been fully established and remains uncertain. This meta-analysis aims to determine the effectiveness of P2Y12 inhibitor monotherapy after short-term DAPT in reducing cardiovascular and bleeding events. Methods A comprehensive search of randomized controlled trials (RCTs) examining the use of short-term DAPT followed by P2Y12 monotherapy in patients with ACS who underwent PCI was conducted. Outcome measures for all-cause mortality, myocardial infarction, and bleeding rates were analyzed using a random-effects model via Review Manager V5.4. Results A total of six randomized controlled trials (RCTs) with 36,724 subjects were analyzed. There were no significant differences in all-cause mortality (RR 0.89 [95% CI: 0.78-1.02], I² = 0%, p = 0.10) and myocardial infarction (RR 1.00 [95% CI: 0.88-1.14], I² = 0%, p = 0.72) between the P2Y12 inhibitor group and dual antiplatelet therapy (DAPT) group. There was a lower rate of major bleeding in the P2Y12 group compared to the DAPT group (RR 0.65 [95% CI: 0.49-0.88], I² = 76%, p = 0.002). The major sources of substantial heterogeneity are due to different intervals of de-escalation and baseline risk factors prior to PCI in each study. Conclusion P2Y12 monotherapy has similar rates of all-cause mortality and myocardial infarction. However, early de-escalation leads to a lower incidence of bleeding. P2Y12 monotherapy showed a 35% decreased risk of bleeding compared to the DAPT strategy. This suggests that P2Y12 monotherapy is a preferable antiplatelet strategy in patients undergoing PCI, especially in the high-risk bleeding population.

Complete vs Culprit-Only Revascularization in Older Patients With Myocardial Infarction and High Bleeding Risk

Patients with high bleeding risk (HBR) have a poor prognosis, and it is not known if they may benefit from complete revascularization after myocardial infarction (MI). To investigate the benefit of physiology-guided complete revascularization vs a culprit-only strategy in patients with HBR, MI, and multivessel disease. This was a prespecified analysis of the Functional Assessment in Elderly MI Patients With Multivessel Disease (FIRE) randomized clinical trial data. FIRE was an investigator-initiated, open-label, multicenter trial. Patients 75 years or older with MI and multivessel disease were enrolled at 34 European centers from July 2019 through October 2021. Physiology treatment was performed either by angiography- or wire-based assessment. Patients were divided into HBR or non-HBR categories in accordance with the Academic Research Consortium HBR document. Patients were randomized to either physiology-guided complete revascularization or culprit-only strategy. The primary outcome comprised a composite of death, MI, stroke, or revascularization at 1 year. Secondary outcomes included a composite of cardiovascular death or MI and Bleeding Academic Research Consortium (BARC) types 3 to 5. Among 1445 patients (mean [SD] age, 81 [5] years; 917 male [63%]), 1025 (71%) met HBR criteria. Patients with HBR were at higher risk for the primary end point (hazard ratio [HR], 2.01; 95% CI, 1.47-2.76), cardiovascular death or MI (HR, 1.89; 95% CI, 1.26-2.83), and BARC types 3 to 5 (HR, 3.28; 95% CI, 1.40-7.64). The primary end point was significantly reduced with physiology-guided complete revascularization as compared with culprit-only strategy in patients with HBR (HR, 0.73; 95% CI, 0.55-0.96). No indication of interaction was noted between revascularization strategy and HBR status for primary and secondary end points. HBR status is prevalent among older patients with MI, significantly increasing the likelihood of adverse events. Physiology-guided complete revascularization emerges as an effective strategy, in comparison with culprit-only revascularization, for mitigating ischemic adverse events, including cardiovascular death and MI. ClinicalTrials.gov Identifier: NCT03772743.

Hepatocellular carcinoma: Advances in systemic therapies.

Advanced hepatocellular carcinoma (HCC) is traditionally associated with limited treatment options and a poor prognosis. Sorafenib, a multiple tyrosine kinase inhibitor, was introduced in 2007 as a first-in-class systemic agent for advanced HCC. After sorafenib, a range of targeted therapies and immunotherapies have demonstrated survival benefits in the past 5 years, revolutionizing the treatment landscape of advanced HCC. More recently, evidence of novel combinations of systemic agents with distinct mechanisms has emerged. In particular, combination trials on atezolizumab plus bevacizumab and durvalumab plus tremelimumab have shown encouraging efficacy. Hence, international societies have revamped their guidelines to incorporate new recommendations for these novel systemic agents. Aside from treatment in advanced HCC, the indications for systemic therapy are expanding. For example, the combination of systemic therapeutics with locoregional therapy (trans-arterial chemoembolization or stereotactic body radiation therapy) has demonstrated promising early results in downstaging HCC. Recent trials have also explored the role of systemic therapy as neoadjuvant treatment for borderline-resectable HCC or as adjuvant treatment to reduce recurrence risk after curative resection. Despite encouraging results from clinical trials, the real-world efficacy of systemic agents in specific patient subgroups (such as patients with advanced cirrhosis, high bleeding risk, renal impairment, or cardiometabolic diseases) remains uncertain. The effect of liver disease etiology on systemic treatment efficacy warrants further research. With an increased understanding of the pathophysiological pathways and accumulation of clinical data, personalized treatment decisions will be possible, and the field of systemic treatment for HCC will continue to evolve.

Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.Graphical

Updated review on malignancy-associated venous thromboembolism: Pathogenesis and comparison between various therapeutic modalities

Venous thromboembolism (VTE) is one of the life-threatening complications in cancer patients, the incidence of which is affected by the patient and malignancy-related variables. Location, type, therapeutic route, stage, grade, and non-supportive treatment of the cancer are the most important VTE risk factors. Patient age, ethnicity, and concomitant genetic or acquired comorbidities or thrombophilias are known risk factors for VTE in cancer. All high-risk cancer patients admitted to hospitals or treated as outpatients should receive VTE prophylaxis. Low molecular weight heparin is the main treatment for active malignant VTE. Vitamin K antagonists and non-Vitamin K-dependent oral anticoagulants are used in stable, non-bleeding cancer patients. Anticoagulation should be continued until the cancer is treated or at least controlled. Over the past two decades, randomized clinical and observational trials have improved the pathogenesis and therapeutic knowledge of VTE, but many challenges remain. The lack of an optimal primary prophylaxis method for inpatients and outpatients in oncology and the care of cancer-associated VTE in standard and high-bleeding risk groups are examples for which more clinical research on cancer-associated thrombosis is necessary to address these issues. In this review, we describe the pathogenesis, factors that increase the risk of VTE, and the comparison between the effectiveness of available anticoagulants in the treatment and prevention of VTE in cancer patients.

Consecutive or selectively included high bleeding risk patients in the MASTER DAPT screening log and trial

AimsScreening logs have the potential to appraise the actual prevalence and distribution of predefined patient subsets, avoiding selection biases, which are inevitably and potentially present in randomised trials and real-world registries, respectively. We aimed to assess the prevalence of high bleeding risk (HBR) characteristics in the real world and the external validity of the MASTER DAPT trial. Methods and resultsAll consecutive patients who underwent percutaneous coronary intervention (PCI) for at least two consecutive weeks across 65 sites participating in the trial were entered into a screening log. Of 2,847 consecutive patients, 1,098 (38.6 %) were HBR and 109 (9.9 %) consented for trial participation. PRECISE-DAPT score ≥ 25 was the most frequent HBR feature, followed by advanced age, use of oral anticoagulation (OAC) and anaemia. Compared with consecutive HBR patients, consenting patients were older (≥ 75 years: 69 % versus 62 %, absolute standardized difference [SD] 0.16), more frequently male (78 % versus 71 %, absolute SD 0.18), had higher use of OAC (38 % versus 20 %, absolute SD 0.39), treatment with steroids or nonsteroidal anti-inflammatory drugs (10 % versus 5 %, SD 0.16), and prior cerebrovascular events (10 % versus 6 %, absolute SD 0.18) but lower PRECISE DAPT score ≥ 25 (54 % versus 66 %, absolute SD 0.24). ConclusionsThe HBR criteria distribution differed between consecutive versus selectively included HBR patients, suggesting the existence of selection biases in the trial population.