Rates Of Major Bleeding Research Articles

Evaluation of safety criteria for enoxaparin bridging in patients with left ventricular assist devices in an outpatient care setting.

Appropriate anticoagulation is crucial for the success of left ventricular assist device patients. Currently, there is no consensus on the optimal management of their subtherapeutic INR in ambulatory setting. Our goal is to evaluate both the short-term adverse events and long-term outcomes of enoxaparin bridging at a major transplant center, following the implementation of bridging safety criteria. In total, 85 patients' medical records were reviewed between 7/2019 and 5/2022, with 51 patients meeting safety criteria were bridged with enoxaparin and 34 non-bridged. The primary endpoint was the occurrence of major bleeding/thrombosis events within 30 days of bridging. The secondary endpoint was freedom from events 30 days after enoxaparin initiation and overall patient survivability until the last follow-up. Within 30 days, no major bleeding/thrombotic events were noted. After 30 days, the major bleeding rate was 5.8% in bridged vs. 11.8% in non-bridged patients (p = 0.02). Overall, 3-year survival was 78% in the bridged vs. 49% in non-bridged patients (p < 0.001). In patients with no events, 3-year survival was 80% in bridged vs. 58% in non-bridged (p < 0.001). In the patients with bleeding events, 3-year survival was 55% in bridged vs. 51% in non-bridged (p = 0.11). At 1 year, freedom from bleeding in the bridged patients was 81% in patients with no events vs. 0% in those with an event (p < 0.0001). When eligibility criteria for safe bridging were applied, the use of enoxaparin bridging was associated with no major bleeding/thrombotic events during bridging and improved 3-year survival in LVAD patients. Economically, using outpatient enoxaparin resulted in substantial healthcare savings, fewer readmissions, and improved quality of life.

Trends in dual antiplatelet therapy regimens and clinical outcomes among patients with acute coronary syndrome undergoing percutaneous coronary intervention with drug‐eluting stents: A multicenter real‐world study

AbstractBackgroundThe patterns of dual antiplatelet therapy (DAPT) use and the associated clinical outcomes in current practice remain limited. This study evaluates DAPT regimen patterns and clinical outcomes among acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI).MethodsThis multicenter retrospective cohort study included ACS patients treated with PCI from January 2017 to February 2022 at five tertiary hospitals in Thailand. DAPT was categorized as nonpotent (NP‐DAPT) or potent (P‐DAPT). We described DAPT trends, with major adverse cardiovascular events (MACEs) and major bleeding, as primary efficacy and safety outcomes. Outcomes were assessed using inverse probability treatment weighting (IPTW) with Cox's proportional hazards model.ResultsThe study included 1877 patients with ACS undergoing PCI. The mean age was 64.51 years (standard deviation 11.34), with 639 (34.04%) female patients and 1159 (61.75%) presenting ST‐elevation myocardial infarction (STEMI). Of these, 924 (49.23%) received NP‐DAPT, and 953 (50.77%) were prescribed P‐DAPT. Crude MACE incidence was lower in the P‐DAPT compared to the NP‐DAPT group (6.82% vs. 10.28%). After applying IPTW and conducting Cox's proportional hazard analysis, no significant differences in MACE were observed between groups (hazard ratio [HR]: 0.85, 95% confidence interval [CI]: 0.58–1.25, p = 0.408), nor in major bleeding (HR: 0.80, 95% CI: 0.37–1.70, p = 0.555). P‐DAPT was associated with any higher bleeding risk (HR: 1.52, 95% CI: 1.13–2.03, p = 0.005).ConclusionStandard DAPT remains predominant among Thai ACS patients, with NP‐DAPT prescriptions approaching those of P‐DAPT. Despite similar rates of MACE and major bleeding between the groups, P‐DAPT was associated with a higher risk of any bleeding.

Efficacy of direct oral anticoagulants vs. warfarin in left ventricular thrombus in myocardial infarction: systematic review and meta-analysis.

Current recommendations for antithrombotic strategies in left ventricular (LV) thrombus following myocardial infarction (MI) remain uncertain. This study aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) compared to warfarin in LV thrombus following MI. A systematic search using four databases, including PubMed, Embase, Web of Science, and Cochrane CENTRAL, was conducted from inception to 8 July 2024, without language restrictions. The inclusion criteria were studies that included patients with LV thrombus following MI and compared the efficacy or safety of DOACs and warfarin. There were 11 studies (3 randomized and 8 nonrandomized) included in this meta-analysis, involving 14 927 participants. We used a random-effects model for this meta-analysis. DOACs were associated with higher thrombus resolution than warfarin, with a risk ratio (RR) of 1.07 [95% confidence interval (CI) 1.00-1.15], P = 0.04. Similarly, DOACs were associated with a lower rate of stroke and systemic embolism, with an RR of 0.84 (95% CI 0.78-0.90), P < 0.01. DOACs also marginally reduced the rate of major bleeding compared with warfarin, with an RR of 0.87 (95% CI 0.75-1.00), P = 0.05. DOACs were associated with higher rates of LV thrombus resolution, lower rates of stroke/systemic embolism, and marginally reduced major and bleeding events compared with warfarin in patients with LV thrombus following acute MI. Therefore, DOACs may be a reasonable alternative to warfarin in this setting.

Comparison of Direct Oral Anticoagulants and Vitamin K Antagonists for Left Ventricular Thrombus: A Global Retrospective Study

IntroductionGuidelines for managing left ventricular thrombus remain limited, particularly when incorporating oral anticoagulants into dual antiplatelet therapy for acute myocardial infarction. This study aims to assess the safety and efficacy of direct oral anticoagulants (DOAC) versus vitamin K antagonist (VKA) in managing left ventricular thrombus among patients with and without recent myocardial infarction. MethodsThis retrospective observational study used data from the TriNetX research network. Patients with left ventricular thrombus treated with either DOACs or VKAs between December 1, 2013, to December 1, 2023, were included. Subgroup analyses were conducted for patients with or without recent acute coronary syndrome (<1 month). Risk and Kaplan-Meier survival analysis were conducted at 90 days since the indexed event. ResultsA total of 39,770 patients were included. DOACs treatment had lower rates of stroke (11.8% vs. 13.7%, RR=0.859, 95% CI 0.816-0.905, p<0.001), major bleeding (4.8% vs. 5.3%, RR=0.902, 95% CI 0.829-0.982, p=0.018), and systemic embolism (3.5% vs. 4.2%, RR=0.841, 95% CI 0.762-0.928, p=0.001) compared to VKAs in overall cohort. Within acute coronary syndrome group (N=14,302), DOACs had lower stroke (12.3% vs. 14.4%, RR=0.860, 95% CI 0.791-0.935, p<0.0001) and systemic embolism (3.1% vs. 4%, RR=0.774, 95% CI 0.651-0.919, p=0.003) risks. For non-acute coronary syndrome group (N=24,162), DOACs had lower stroke (11.4% vs. 13.1%, RR=0.868, 95% CI 0.811-0.929, p<0.001) and major bleeding (4.8% vs. 5.5%, RR=0.877, 95% CI 0.787-0.977, p=0.017) risks. No significant differences in all-cause mortality were observed across groups. ConclusionDOACs demonstrated better safety and efficacy outcomes when compared to VKAs in left ventricular thrombus treatment, with or without recent acute coronary syndrome.

035. Short-Term Outcomes for Catheter-Directed Thrombolysis for Non-Threatening Acute Limb Ischaemia: A Systematic Review and Meta-Analysis

Background: Acute limb ischemia (ALI) is a rapid reduction in arterial blood flow to a limb, which may jeopardize its viability, particularly in sensory loss or motor impairment. Catheter-directed thrombolysis (CDT) is the preferred treatment in numerous centers for patients with marginally threatening acute limb ischemia (ALI). This meta-analysis examined the short-term effects of catheter-directed thrombolysis (CDT) for patients with non-imminent limb ischemia. Methods: We searched PubMed, ScienceDirect, and the Cochrane Library to locate observational papers and trials published from 2014 up to early 2024 that report on the outcomes of CDT in patients with ALI. The outcome of this study was mortality rate, amputation rate, and major bleeding. We utilized R Studio to perform the meta-analysis. Results: Nine trials were included, involving 1,067 patients receiving CDT for non-imminent acute limb ischemia. Our results indicate that the pooled mean short-term amputation rate was 10% (95% CI [0.06; 0.15], p &lt; 0.01), the major bleeding rate was 5% (95% CI [0.00; 0.09], p = 0.03), and the short-term death rate was 4% (95% CI [0.03; 0.06], p = 0.08). Our findings indicate a low incidence of short-term death, amputation, and major bleeding in patients undergoing CDT. Conclusion: This meta-analysis reveals a low incidence of short-term mortality, amputation, and major bleeding in patients undergoing Catheter-directed thrombolysis. Further investigations are necessary to determine if CDT should be utilized for the revascularization of limbs with non-urgent ischemia.

Recent secular trends of catheter-directed therapy for treatment of pulmonary embolism: a retrospective cohort study based on German national data

Abstract Background Various approaches exist for treatment of pulmonary embolism, including systemic lysis, catheter-directed therapy, or anticoagulation. Purpose This study aimed to describe recent secular trends of treatment strategies for patients with pulmonary embolism. Methods Data were interrogated from the Research Data Centre of the German Federal Statistical Office by ICD- and OPS-codes. 800,119 patients with pulmonary embolism, who were treated in German hospitals between 2007 and 2021, were analyzed and grouped according to the therapeutic strategy: no lysis or intervention, systemic lysis, ultrasound-assisted thrombolysis, catheter-directed lysis without ultrasound, retriever system, other transluminal thrombus removal, or surgical thrombectomy. In-hospital outcomes were investigated with focus on the last 8 years. Results Of all patients examined, 37,885 were treated with systemic lysis, 1,383 with ultrasound-assisted thrombolysis, 2,520 with catheter-directed lysis without ultrasound, 181 with a retriever system, 695 with other transluminal thrombus removal, and 1,037 with surgical thrombectomy. There was an increase in all catheter-directed therapies between 2007 and 2021 (from 102 to 735 procedures per year) with more than twice as many procedures from 2019 to 2021 (from 343 to 735 procedures). Between 2014 and 2021, 453,893 patients with main diagnosis of pulmonary embolism were included in the analysis. Mean age was 58.4-68.1 years in the observed groups. 42.5-52.2% were female. Highest rates of cor pulmonale were observed in patients undergoing surgical thrombectomy (87.7%) and systemic lysis (80.1%), which also applied to shock (26.2% and 25.7%), while both rates were lowest in patients without lysis or intervention (cor pulmonale: 25.4%, shock: 1.8%). The overall in-hospital mortality rate was 8.3%, ranging between 6.5% in the ultrasound-assisted thrombolysis group and 38.4% in the systemic lysis group. In catheter-directed therapies, the rate of major bleeding (&amp;gt;5 units of red blood cells) was 4.9%, ranging from 3.1% for catheter-directed lysis without ultrasound to 10.1% for other transluminal thrombus removal. The rate of intracerebral bleeding was 1.4%, with 0.0% for ultrasound-assisted thrombolysis and 4.4% for treatment with a retriever system. Conclusion In recent years, the use of catheter-directed therapy for pulmonary embolism has steadily increased. Rates of in-hospital major bleeding events and intracerebral bleeding were low.

Oral anticoagulants or antiplatelets for cryptogenic stroke: a systematic review and meta-analysis

Abstract Background Cryptogenic strokes comprise 20 to 30% of ischemic strokes and include a substantial proportion classified as embolic stroke of undetermined source (ESUS). However, the optimal antithrombotic strategy for cryptogenic stroke remains contentious. Purpose We conducted a systematic review and meta-analysis to compare the efficacy and safety of oral anticoagulants (OAC) versus antiplatelets in patients with cryptogenic stroke. Methods Six electronic databases of PubMed, Embase, Web of Science, the Cochrane Library, Google Scholar and ClinicalTrials.gov were searched from inception to Feb 15, 2024 to identify relevant randomized controlled trials (RCTs) comparing stroke recurrence and major bleeding rates between OAC and antiplatelets in cryptogenic stroke patients. We included trials adhering to a stringent diagnostic work-up for cryptogenic stroke, defined as cerebral infarction not attributed to definite sources of cardioembolism, large artery atherosclerosis, or small artery disease despite undergoing comprehensive investigations. The primary outcome was recurrent ischemic stroke, and the secondary outcome was major bleeding based on International Society of Thrombosis and Hemostasis criteria. Subgroup analysis was conducted for ESUS patients with an increased risk of cardiac emboli, such as patent foramen ovale (PFO) and atrial cardiopathy, defined as lead V1 terminal P-wave &amp;gt; 5000 μV × ms in electrocardiogram, serum N-terminal pro-B-type natriuretic peptide level &amp;gt; 250 pg/mL, and left atrial diameter (LAE) &amp;gt; 4 cm, or LAE index ≥ 3 cm/m2 on echocardiogram. Hazard ratio (HR) with 95% confidence (CI) was used as a measure of the effect estimates for aforementioned outcomes. Random-effects meta-analysis was performed using a restricted maximum likelihood model given between-study variance is inevitable. Results Our meta-analysis included 9 RCTs with a total of 15,139 patients (OAC = 7,343; antiplatelets = 7,796). ARCADIA, RE-SPECT ESUS, and NAVIGATE ESUS Trial investigated apixaban, dabigatran, and rivaroxaban, respectively, while warfarin was primarily used as OAC in the remaining six trials. Aspirin was predominantly utilized for antiplatelet therapy. There was no significant difference in recurrent ischemic stroke between OAC and antiplatelets (HR, 0.90; 95% CI, 0.78 to 1.04; I2 = 0%). However, OAC use was associated with a significantly higher risk of major bleeding (HR, 1.66; 95% CI, 1.07 to 2.56; I2 = 36%). Subgroup analysis in ESUS patients revealed comparable rates of recurrent ischemic stroke in those with atrial cardiopathy (HR, 0.91; 95% CI, 0.65 to 1.29; I2 = 0%) and PFO (HR, 0.72; 95% CI, 0.49 to 1.07; I2 = 0%). Conclusions Our meta-analysis suggests that OAC use does not decrease the risk of recurrent ischemic stroke compared with antiplatelet use but is associated with a significantly higher risk of major bleeding in patients with cryptogenic stroke.Primary (A) and secondary (B) outcomesSubgroup analysis for recurrent stroke

Ischemic and bleeding risk after ST-segment elevated myocardial infarction in patients with active cancer

Abstract Background Treatment of patients with cancer presenting with ST-elevation myocardial infarction (STEMI) is complex given the increased risk of both thrombotic and major bleeding complications. We evaluated the risk of major bleeding and re-infarction in patients with or without cancer following admission with STEMI Methods A nationally-linked cohort of STEMI patients between January 2005 and March 2019 were obtained from the UK Myocardial Infarction National Audit Project (MINAP) registry and the UK national Hospital Episode Statistics Admitted Patient Care (HES APC) registry. Cox proportional hazard models were used, and Kaplan-Meier survival and cumulative survival curves were constructed. Results A total of 322,776 STEMI indexed admissions were identified between Jan 2005 and March 2019. Of those, 7050 (2.2%) patients were diagnosed with active cancer. Cancer patients were older with more cardiovascular comorbidities. Cancer patients received invasive coronary angiography (62.2% vs 72.7%, p&amp;lt;0.001) and PCI (58.4% vs 69.5%) less often compared to patients without cancer and were less likely to be prescribed DAPT (85% vs 95.4%). Major bleeding rate at one year was higher in cancer patients (6.5% vs 3.5%) while re-infarction rates were similar (cancer 5.7%, no cancer 5.1%). Adjustment for differences in baseline covariates, a similar risk of re-infarction (SHR 1.10, 95% CI 0.94-1.27) and a 50% increased risk of major bleeding (SHR 1.49, 95% CI 1.30-1.71) was observed in cancer patients. Conclusion Compared to non-cancer patients, cancer patients have a higher risk of major bleeding but not of re-infarction. Mitigating bleeding risk in STEMI patients with cancer is of paramount importance to improve outcomes.bleeding risk at 1 yearRe-infarction risk at 1 year

Stratification of residual thromboembolic risk among anticoagulated atrial fibrillation patients: a hierarchical cluster analysis from a global, real-world population

Abstract Background Assessment of residual thromboembolic risk among atrial fibrillation (AF) patients despite being on oral anticoagulants (OACs) poses a significant challenge. This study utilises a hierarchical cluster analysis approach to identify risk phenotypic profiles in a global prospective AF registry. Methods Data were drawn from recently diagnosed non-valvular AF patients receiving OACs, as recorded in phases II and III of the GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) registry. A hierarchical cluster analysis based on patient demographics was performed to identify distinct phenotypes. The incidence and risks of thromboembolic events (ischaemic stroke, transient ischaemic attack, or systemic embolism) and relevant events (major bleeding and all-cause death) were compared across clusters. Results The study included 22,410 patients (mean age 70±8 years; 56% male), from which 5 phenotypes were delineated: Cluster 1 ("uncontrolled hypertension"), Cluster 2 ("young with a history of coronary artery disease"), Cluster 3 ("young and obese"), Cluster 4 ("frailty"), and Cluster 5 ("non-paroxysmal AF with tachycardia"). Cluster 4 was associated with the highest rates of thromboembolic events (1.66/100 person-years), major bleeding (1.92/100 person-years), and all-cause mortality (6.02/100 person-years). Conversely, Cluster 3 showed the lowest risk profiles across all outcomes (thromboembolic events: 0.64 events/100 person-years, major bleeding: 0.83 events/100 person-years, and all-cause death: 1.44 events/100 person-years). Cluster 1 displayed a moderate thromboembolic event rate (1.04/100 person-years), although lower rates were observed in Clusters 2 and 5 (Figure 1). Conclusions Hierarchical cluster analysis effectively identified distinct phenotypes within a global AF population, offering valuable insights for stratifying the risks of residual thromboembolic events and other significant outcomes in anticoagulated AF patients (Figure 2).Figure 1Figure 2

Haemorrhagic risk in elderly patients with atrial fibrillation that develop low platelet count during direct oral anticoagulant treatment: insights from the ATHERO-AF study

Abstract Background Bleeding risk in atrial fibrillation (AF) patients is complex and dynamic. Among others, thrombocytopenia has been suggested as a bleeding risk factors. No data on thrombocytopenia occurring during direct oral anticoagulants (DOACs) therapy are available. Purpose We investigated the incidence rate of thrombocytopenia and major bleeding (MB) in AF patients on DOACs. We also investigated whether the addition of incident thrombocytopenia to the HAS-BLED score might increase its predictive value compared to baseline HAS-BLED calculation. Methods 955 AF patients from the prospective ongoing ATHERO-AF study followed for a mean of 38.4±26.6 months. All patients were on DOACs. Thrombocytopenia was defined by a platelet count &amp;lt;150 x109/L registered during follow-up visits. MB events were defined according to ISTH definition and were recorded at each follow-up visit. Patients with thrombocytopenia at baseline were excluded. Multivariable Cox proportional hazards regression analysis was used to calculate the hazard ratio (HR) with 95% Confidence interval (95%CI) for each factor in relation to bleeding risk. Results Mean age was 77.3±9.0 years and 40.1% were women. During a follow-up, 139 patients developed thrombocytopenia with an incidence rate of 0.8% per year. We recorded no difference between thrombin and factor Xa inhibitors. During follow-up, 179 bleedings occurred, of which 80 were major. Patients experiencing bleedings were more likely to suffer from arterial hypertension, heart failure, anaemia and had higher CHA2DS2-VASc and HAS-BLED scores. At multivariable Cox proportional hazards regression analysis, factors associated with MB were incident thrombocytopenia (HR 1.995, 95%CI 1.211-3.288), antiplatelet use (HR 2.716 95%CI 1.269-5.816) and age (HR 1.033, 95%CI 1.003-1.064). The addition of incident thrombocytopenia to the HAS-BLED score increased the predictive value of baseline HAS-BLED in patients without thrombocytopenia for MB events (AUC from 0.54 to 0.61, p=0.016). Conclusion Incident thrombocytopenia is associated with an increased risk of MB. The addition of incident thrombocytopenia to the baseline HAS-BLED score increased its predictive value, suggesting that continuous bleeding risk evaluation of AF patients may provide additional prognostic information compared to the baseline only.

Resolution of silent left atrial thrombi and clinical outcomes in patients with atrial fibrillation: insight from the LAT trial

Abstract Background Silent thrombi in the left atrium (LA), which are thrombi that have not yet caused thromboembolism, are occasionally observed in patients undergoing transesophageal echocardiography (TEE) for atrial fibrillation (AF). However, there is limited data regarding the impact of resolving these silent LA thrombi (LAT) on patient outcomes. Methods We conducted a retrospective review of clinical records from 2010 to 2018 at six hospitals, involving 17,436 TEE procedures for patients with AF. Among these, 297 patients (1.7%) were identified with silent LAT. Of these, 169 patients with follow-up TEE or cardiac computed tomography data for assessing the resolution of LAT were included in this study. The study population were categorized into two groups: the successful resolution group, defined as those with complete LAT resolution without any related events (N=130), and the failed resolution group (N=39). The latter included patients with residual LAT at the last follow-up (N=26), individuals with thromboembolic events (N=8), or those who required surgical intervention for LAT (N=5). Results During the median follow-up period of 394 days (interquartile range, 373-421 days) following thrombi detection, ischemic stroke and systemic thromboembolism (IS/SE) were observed in 10 cases, major bleeding in 23 cases, and all-cause death in 8 cases. In comparison to the successful resolution group, the failed resolution group not only exhibited a higher incidence of IS/SE (1.5% in the successful vs. 20.5% in the failed resolution group, Log-rank p &amp;lt; 0.001) but also showed trends toward increased major bleeding (10% vs. 23.1%, p = 0.033) and higher total mortality rates (3.1% vs. 10.3%, p = 0.05). These differences in composite endpoints were also statistically significant (13.9% vs. 35.9%, p = 0.001). Conclusion In patients with silent LATs were identified, non-resolution of these LATs was associated with not only a higher incidence of IS/SE but also increased rates of major bleeding and all-cause mortality. Conversely, patients who experienced LAT resolution exhibited more preferable prognoses. The status of LAT resolution is closely associated with patient outcomes, underscoring the importance of monitoring LAT resolution in stratifying patient prognoses.

Baseline characteristics, management patterns and outcome in patients with pulmonary embolism and malignancy: Insights from a single-centre study

Abstract Background and aim The presence of malignancy is an important factor that increases the risk of venous thromboembolism. On the other hand, acute pulmonary embolism (PE) is one of the main causes of death in this setting. In this study, we evaluated the impact of active malignancy on the treatment choices, and short and long term clinical outcomes in patients with acute PE. Methods In this study conducted in a tertiary center, 872 acute PE patients (age 61.6±16.8 years, female 57.5 %) from different risk categories were treated with thrombolytic, anticoagulant and catheter-based therapies in accordance with currently available acute PE guidelines. The population was retrospectively analyzed and divided into two groups according to the presence of active malignancy. Results Active malignancy was documented in 129 (14.8 %) patients. In the groups with and without malignancy, the proportions of low-, intermediate-low-, intermediate-high-, and high-risk PE patients were 3.1 % vs. 15.6 %, 17.8 % vs. 16.7 %, 60.5 % vs. 60 %, and 18.6 % vs. 7.7 %, respectively (p&amp;lt;0.001). While the two groups did not differ in terms of echocardiographic and computed tomographic pulmonary angiography (CTPA) characteristics, the presence of contraindications for thrombolytic were more frequent in the malignancy group (22.5% vs. 10.9%, p&amp;lt;0.001). Ultrasound-assisted thrombolysis (USAT), rheolytic thrombectomy (RT), systemic thrombolysis (ST) and anticoagulation-alone (AC) therapies were noted in 27.3 %, 6.4 %, 6.4 % and 49.7 % of overall PE patients. The RT and AC therapies were more frequent in PE patients with malignancy whereas ST and USAT were more frequently used in the absence of malignancy. Notably, lytic dosages and treatment durations in USAT and ST protocols were comparable between malignant and non-malignant PE cohorts. Regardless of the presence of malignancy and the treatment modality chosen, significant improvements were achieved in the clinical, echocardiographic and CTPA measures of the PE severity (p&amp;lt;0.001 for all). Major and minor bleeding rates were also similar in both groups, while in-hospital and, as expected, long-term mortality were higher in the malignancy cohort. Active malignancy and PESI score were found to be independent predictors for composite end-point of 60-day mortality and PE-related rehospitalization (adjusted odds ratio (OR): 2.43; 95 % CI: 1.32 - 4.47, p=0.04) and (OR: 1.02; 95 % CI: 1.01-1.01, p&amp;lt;0.001), respectively. Malignancy (OR: 3.5, 95 % CI: 2.15-5.75, p&amp;lt; 0.001) and chronic obstructive pulmonary disease (OR: 2.51, 95 % CI: 1.35-4.68, p&amp;lt; 0.003) were independent predictors of long-term mortality. Conclusion Concomitant malignancy adversely affects both short- and long-term outcomes in patients with acute PE. Although these patients are more vulnerable, it is possible to achieve satisfactory treatment success with acceptable bleeding rates with the inclusion of catheter-based methods as treatment option.Survival plot

Evaluation of the biomarker-based ABC-AF-bleeding risk score and clinically based bleeding scores in 31,605 patients with atrial fibrillation treated with oral anticoagulation

Abstract Background International guidelines recommend a systematic evaluation of bleeding risk in patients with atrial fibrillation (AF) to guide oral anticoagulation. However, it remains challenging to accurately predict bleeding risk. The biomarker-based ABC-AF-bleeding risk score to predict bleeding in anticoagulated patients with AF has shown promise. Purpose To evaluate the performance of the biomarker-based ABC-AF-bleeding risk score and compare its performance with other bleeding risk scores in 31,605 patients randomized to direct oral anticoagulant or warfarin using individual patient data from three randomized clinical trials. Methods The COMBINE AF biomarker data set contains individual patient data from three pivotal randomized trials (ARISTOTLE, ENGAGE AF-TIMI 48, and RE-LY) comparing apixaban, edoxaban or dabigatran with warfarin, in patients with AF at increased risk of stroke. The ABC-AF-bleeding biomarkers were analyzed in plasma samples collected at baseline (hemoglobin, troponin T high-sensitivity, and GDF-15) using Roche Diagnostics Elecsys assays. The biomarker-based ABC-AF-bleeding risk score (Age, Biomarkers, Clinical history of prior bleeding) was calculated as previously published. The discrimination was assessed by Harrell’s c index and compared with three clinically based bleeding risk scores; HASBLED, ORBIT, and DOAC. Results During a median follow-up time of 2.0 years, a total of 1,572 ISTH major bleeding events occurred (incidence rate per 100 person-years of 2.79) including 593 gastrointestinal (1.04) and 270 intracranial (0.47) bleeding events. The biomarker-based ABC-AF-bleeding score was well calibrated for major bleeding in the total material (Figure). The c indices for major bleeding were 0.68 (95% confidence interval 0.67-0.70), for gastrointestinal bleeding 0.70 (0.68-0.72), and for intracranial bleeding 0.66 (0.63-0.69). The biomarker-based ABC-AF-bleeding risk score provided superior discrimination compared with the clinically based risk scores in the full cohort (Table). The ABC-AF-bleeding risk score also provided superior discrimination for major bleeding in clinically relevant subgroups based on age, sex, body mass index, coronary artery disease, diabetes, heart failure, kidney function, and irrespective of DOAC or VKA use. Conclusions In patients with AF treated with different types of OAC the biomarker-based ABC-AF-bleeding score provide better discrimination of the risk för major bleeding than risk scores based only on clinical factors. The results were consistent for different types of bleeding and across multiple subgroups. There was good calibration when comparing predicted vs observed rate of major bleeding. These findings support the utility of the biomarker-based ABC-AF-bleeding risk score for advancing precision medicine in patients with AF.Calibration of ABC-AF-bleeding scoreTable

Clinical outcomes of edoxaban treatment in atrial fibrillation patients with high bleeding risk: insights from the ETNA-AF-China 1-year follow-up

Abstract Background In China and many other countries, anticoagulated atrial fibrillation (AF) patients with high bleeding risk often raises clinical concern; the optimal dose of direct oral anticoagulants (DOACs) preventing stroke/systemic embolic events (SEE) in those population remains unclear. Purpose To assess the effectiveness and safety of edoxaban treatment in Chinese AF patients with high bleeding risk, and to compare 60 mg vs 30 mg dose in this real-world registry. Methods ETNA-AF-China is a prospective, observational study conducted in 89 centres across Chinese Mainland enrolling AF patients receiving edoxaban. This subgroup analysis was based on 1-year follow-up data. Patients were categorized to high bleeding risk group who had a DOAC score ≥6 (age, creatinine clearance, underweight, history of stroke/TIA/SEE, diabetes, hypertension, antiplatelet use, NSAIDs use, history of major/critical bleeding, liver disease) at baseline, or moderate-to-low bleeding risk group meeting criteria of DOAC score &amp;lt;6. The safety, effectiveness, and composite outcomes were reported by comparison between patient subgroups using Cox proportional hazards models. Results Of 4883 patients with 1-year follow-up, 1534 (31.4%, 60 mg: n=518, 30 mg: n=1016) were identified as high bleeding risk and 3349 (68.6%) as moderate-to-low bleeding risk. As expected, patients with high bleeding risk were more often elderly (48.2% ≥80 years), had lower body weight, worse renal function, higher CHA2DS2-VASc score than those with moderate-to-low risk (Figure 1). In both high risk and moderate-to-low risk subgroups, patients receiving 60 mg edoxaban were younger, with better renal function, lower CHA2DS2-VASc score compared with 30 mg. Annualised event rates of major bleeding (HR 2.95, 95%CI 1.62–5.36), all cause death (3.42, 2.29–5.09), CV death (3.27, 1.52–7.04), major adverse cardiac events (MACE, 2.61, 1.69–4.02) and all NCOs were significant higher in patients with high bleeding risk compared with moderate-to-low risk (Figure 2). After multivariable adjustment, edoxaban dose of 60 mg other than 30 mg were associated with significantly lower rates of all cause death (adjusted HR 0.41, 0.18–0.90) and lower trend of NCO3 (0.51, 0.28–0.92) and NCO4 (0.51, 0.30–0.88) by composite of stroke/SEE, major bleeding and death events in high risk subgroup; no significant difference between edoxaban doses and stroke or bleeding outcomes with cumulative low event rates were observed. Conclusion In routine clinical care, AF patients at high bleeding risk faces worse outcomes of death events, MACE, as well as the composite outcomes over moderate-to-low risk patients. Among patients with high bleeding risk, edoxaban use showed effectiveness and safety with overall low incidence, and potential better survival, composite endpoint benefit could be associated with 60mg. Further investigation is ongoing.

Impact of body weight and body mass index on clinical outcomes of edoxaban therapy in atrial fibrillation patients included in the ETNA-AF-Global registry

Abstract Background In atrial fibrillation (AF) patients (pts) receiving non-vitamin K antagonist oral anticoagulant therapy, extreme body weights, both obesity and low body weight, may impact clinical outcomes. Purpose To determine the impact of body weight and body mass index (BMI) on clinical outcomes in AF pts receiving edoxaban from the Global ETNA program (Europe [NCT02944019], Japan [UMIN000017011], Korea/Taiwan [NCT02951039], Hong Kong [NCT03247582] and Thailand [NCT03247569]). Methods ETNA-AF-Global, a multinational, prospective, observational study collected demographic and clinical outcomes data for AF pts receiving edoxaban. In this subanalysis, pts were categorised into the following body weight groups: ≤60kg, &amp;gt;60 to 80kg (reference body weight), &amp;gt;80 to ≤100kg and &amp;gt;100kg; and BMI groups: &amp;lt;18.5kg/m², ≥18.5 to &amp;lt;25.0kg/m² (reference BMI), ≥25.0 to &amp;lt;30.0kg/m², ≥30.0 to &amp;lt;40.0kg/m² and ≥40.0kg/m². Clinical outcomes at 2-year follow-up were compared across body weight and BMI groups. Results 26,805 pts were included in this analysis. Mean ± standard deviation body weight was 72.2 ± 18.1kg and mean BMI was 26.4 ± 5.0kg/m². 43.7% of pts were categorised into the &amp;gt;60 to 80kg reference body weight group. [other groups: ≤60kg, 28.1%; &amp;gt;80 to ≤100kg, 21.7%; &amp;gt;100kg, 6.5%] and 40.0% of pts into the ≥18.5 to &amp;lt;25.0kg/m² reference BMI group [other groups: &amp;lt;18.5kg/m², 3.0%; ≥25.0 to &amp;lt;30.0kg/m², 37.3%; ≥30.0 to &amp;lt;40.0kg/m², 18.0%; ≥40.0kg/m², 1.7%]. Clinical outcomes are shown in Fig. 1 as unadjusted hazard ratios vs. reference group according to weight and in Fig. 2 according to BMI. Among body weight groups, pts weighing ≤60kg had the highest annualised rates of any stroke or systemic embolic event (SEE; 1.24%), ischemic stroke (0.97%), all-cause death (3.96%), major bleeding events (1.49%), and major bleeding or clinical-relevant non-major (CRNM) bleeding events (3.45%). Pts in the reference body weight group had the lowest annualised rates of all-cause death (2.81%). Annualised rates of major bleeding, major bleeding or CRNM bleeding events and any stroke or SEE were lowest in pts weighing &amp;gt;100kg. Among BMI groups, annualised rates of all effectiveness and safety outcomes were highest in pts with a BMI &amp;lt;18.5kg/m². Pts in the ≥25.0 to &amp;lt;30.0kg/m² BMI group had the lowest annualised rates of all-cause death (2.85%) and pts in the ≥18.5 to &amp;lt;25.0kg/m² BMI group had the lowest annualised rates of CV death (0.73%). Conclusions In the Global ETNA-AF program, clinical outcomes varied between different body weight and BMI subgroups. These findings highlight the need to consider the clinical implications of low body weight and/or low BMI, as AF pts who belong to these categories may be at higher risk of adverse outcomes during long-term anticoagulant treatment.Figure 1.Figure 2.

Prognostic implications of p2y12 inhibitor pre-treatment in non-st segment elevation acute coronary syndromes undergoing late invasive strategy - a national registry analysis

Abstract Background Current guidelines recommend considering P2Y12 pre-treatment (PreT) in patients (pts) with non-ST segment elevation acute coronary syndrome (NSTE-ACS) expected to undergo a late invasive strategy, based on individual bleeding risk. Purpose Investigate in-hospital morbidity and mortality in NSTE-ACS pts undergoing a late invasive strategy (coronary angiography (CAG) performed &amp;gt;24h post-admission) comparing those receiving P2Y12 inhibitors (P2Y12i) PreT with those who did not. Methods Retrospective multicenter analysis of NSTE-ACS pts from the Portuguese Registry on Acute Coronary Syndromes (ProACS) undergoing a late invasive strategy from October 2010 to October 2023. Exclusion criteria: previous treatment with P2Y12i or anticoagulants; atrial fibrillation. Two cohorts were defined: pts receiving PreT with P2Y12i before undergoing CAG (group 1) and pts without PreT (group 2). Comparative analyses included baseline characteristics, clinical findings, CAG findings and treatment. Primary outcome was in-hospital major adverse cardiovascular events (MACE), a composite of all-cause mortality, re-infarction, stroke and congestive heart failure. The secondary outcome included individual events and major bleeding. Results 3776 pts were included (mean age:66±12 yrs,29% female), 1530 in group 1 and 2246 in group 2. Group 1 had lower prevalence of dyslipidemia (60 vs 66%, p&amp;lt;0.001), prior stroke (7 vs 5%, p=0.003), myocardial infarction (16 vs 21%) and percutaneous coronary intervention (12 vs 15%) (both p=0.001). On admission, there were no differences regarding Killip-Kimball class (class I - 90 vs 90%,p=0.501) and pts in group 1 less frequently had left ventricular disfunction (left ventricular ejection fraction &amp;lt;50% - 20 vs 24%,p=0.032). Group 1 had higher incidence of obstructive CAD (84 vs 77%,p&amp;lt;0.001), more frequently required more than 1 CAG during admission (8 vs 4%,p&amp;lt;0.001), but multivessel disease did not significantly differ (52 vs 52%,p=0.667). Coronary angioplasty was more frequent in group 1 (63 vs 60%,p=0.019) as was coronary artery bypass graft (13 vs 10%,p=0.002). Regarding anti-thrombotics, group 1 had higher prescription rates of clopidogrel (68 vs 56%), aspirin (99 vs 81%), unfractionated heparin (21 vs 8%), enoxaparin (80 vs 56%), but lower of fondaparinux (12 vs 41%) (all p&amp;lt;0.001). There were no differences in the primary outcome (9 vs 9%,p=0.906) and secondary outcomes: in-hospital mortality (1 vs 1%), re-infarction (1 vs 1%), ischemic stroke (1% vs 0,4%) and congestive heart failure (7% vs 8%) (all p&amp;gt;0.05). Group 1 had higher rates of major bleeding (0.8 vs 0.2%, OR 3.48, CI 95% 1.22-9.89, p=0.013). Conclusions In patients with NSTE-ACS undergoing a late invasive strategy, PreT with P2Y12i showed no statistically significant differences in MACE, despite association with higher rates of major bleeding.Baseline characteristicsPrimary and secondary outcomes

Two different hybrid vascular access closure strategies post transcatheter aortic valve implantation

Abstract Background The hybrid strategy combining plug-based and suture-based vascular closure devices (VCD) was introduced as a promising technique for vascular access hemostasis after transcatheter aortic valve implantation (TAVI) with satisfactory outcomes. However, data comparing two plug-based VCDs each in the combination with a suture-based VCD, namely ProGlide/FemoSeal (P/FS) with ProGlide/AngioSeal (P/AS) VCDs, is still lacking. Aim To compare the 30-day outcome of the hybrid strategy using P/AS versus P/FS for vascular access site closure after TAVI. Methods A retrospective single Centre observational study included 608 patients recruited from a prospective TAVI registry between 2016 and 2022. The composite endpoint was defined as any VCD related major vascular complications and/or bleeding more than type 1 according to Valve Academic Research Consortium (VARC-3) criteria. Results The current study reported a significantly higher rate of composite endpoint in P/AS group, which was driven by higher rate of major bleeding (5.4% vs 1.4%, p=0.036). We also found a higher rate of VCD related minor bleeding in P/AS group (16.3% vs 8.1%, p=0.013). Successful access site hemostasis was achieved in 83.1% of P/FS group versus 71.7% in P/AS group (p=0.006). The presence of anterior wall calcification at the access site was significantly associated with the composite endpoint (adj OR 2.49; 95% CI (1.08 – 5.75), p=0.032). Conclusions The hybrid strategy for large bore vascular access closure using P/FS showed a potentially better 30-day outcomes compared with P/AS. The presence of anterior calcification at the access site carries a significant risk of VCD related complications.

Bleeding and Thrombotic Events in Hemodialysis Patients with Atrial Fibrillation on Anticoagulation and Antiplatelet Therapy: A 24-Month Cohort Study

Background and Objectives: Patients undergoing chronic hemodialysis (HD) are predisposed to both thrombotic and bleeding complications due to the complex interplay of end-stage renal disease (ESRD), cardiovascular comorbidities, and the routine use of anticoagulant and antiplatelet therapies. This study aimed to investigate the incidence of bleeding and thrombotic events in chronic HD patients receiving anticoagulant and antiplatelet therapy, with a specific focus on those with atrial fibrillation (AF). Materials and Methods: A total of 224 patients, with 43 (19%) of them diagnosed with AF, were included in this single-center, observational cohort study conducted over 24 months. The cohort was divided into three groups: patients without anticoagulation, those on warfarin monotherapy, and those on combined warfarin and aspirin therapy. Bleeding events were classified as major, clinically relevant non-major bleeding (CRNMB), or minor bleeding, while thrombotic events included ischemic stroke, myocardial infarction, pulmonary embolism, and arteriovenous fistula thrombosis. Results: Overall, 35.7% of patients experienced a bleeding event, with major bleeding occurring in 9.4%. Patients with AF had significantly higher rates of major bleeding (18.6%) compared to those without AF (7.18%; p = 0.043), especially in the combined therapy group. Mortality due to bleeding was also higher in AF patients (14%). In contrast, thrombotic events occurred in 26.8% of patients, with AF patients experiencing significantly more events (48.8%) compared to non-AF patients (21.5%; p = 0.0006). The hazard ratio (HR) for major bleeding in patients on combined warfarin and aspirin therapy was 2.56 (p = 0.016), while the HR for thrombotic events was 2.34 (p = 0.0202). Conclusions: These findings highlight the increased risks of both bleeding and thrombosis in chronic HD patients with AF, particularly those on combined anticoagulation and antiplatelet therapy.

IVUS-Guided vs Angiography-Guided PCIin Patients With Diabetes With AcuteCoronary Syndromes: The IVUS-ACS Trial.

Intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) reduces the risk for clinical events in patients with acute coronary syndromes (ACS), compared with angiographic guidance. However, the benefits of IVUS guidance in high-risk patients with diabetes with ACS is uncertain. The aim of this prespecified stratified subgroup analysis from the IVUS-ACS randomized trial was to determine the effectiveness of IVUS-guided PCI vs angiography-guided PCI in patients with diabetes with ACS. From August 20, 2019, to October 27, 2022, 1,105 patients with diabetes with ACS were randomized, including 554 patients in the IVUS-guided group and 551 in the angiography-guided group. The primary endpoint was the rate of target vessel failure (TVF) at 1 year, defined as the composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. At 1-year follow-up, TVF occurred in 20 patients in the IVUS guidance group and in 46 patients in the angiographic guidance group (Kaplan-Meier rates 3.6% vs 8.3%; HR: 0.46; 95%CI: 0.27-0.81; P=0.007), driven by a reduction in clinically driven target vessel revascularization (0.9% vs 3.8%; P=0.003). IVUS-guided PCI also reduced the risk for TVF without procedural myocardial infarction (2.0% vs 6.7%; HR: 0.29; 95%CI: 0.15-0.57; P< 0.001) and all-cause mortality (HR: 0.30; 95%CI: 0.10-0.93; P=0.037). There were no significant differences in the rates of stent thrombosis or major bleeding between the groups. In the large-scale IVUS-ACS trial, IVUS-guided PCI improved 1-year clinical outcomes in high-risk patients with diabetes with ACS. (1-Month vs 12-Month DAPT for ACS Patients Who Underwent PCI Stratified by IVUS: IVUS-ACS and ULTIMATE-DAPT Trials; NCT03971500).

Renal Function-Stratified Comparison of Short- and Long-Term Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention With Third-Generation Drug-Eluting Stents - Post Hoc Analysis From the HOST-IDEA Randomized Clinical Trial.

The optimal duration of dual antiplatelet therapy (DAPT) in patients with chronic kidney disease undergoing percutaneous coronary intervention (PCI), especially with third-generation drug-eluting stents (DES), remains unknown. We conducted a prespecified post hoc analysis of the HOST-IDEA trial, randomizing patients undergoing PCI with third-generation DES to 3- to 6-month or 12-month DAPT. In all, 1,997 patients were grouped by their estimated glomerular filtration rate (eGFR): high (>90 mL/min/1.73 m2), intermediate (60-90 mL/min/1.73 m2), and low (<60 mL/min/1.73 m2). The primary outcome was net adverse clinical events (NACE), a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding (Bleeding Academic Research Consortium Type 3 or 5) at 12 months. Secondary outcomes were target lesion failure (TLF) and major bleeding. The low eGFR group had the highest rates of NACE, TLF, and major bleeding compared with the other 2 groups (P<0.001). Rates of NACE were similar in the 3- to 6-month and 12-month DAPT in the high (2.9% vs. 3.2%; P=0.84), intermediate (2.1% vs. 2.8%, P=0.51), and low (8.9% vs. 9.1%; hazard ratio 0.99; P=0.97; Pinteraction=0.88) eGFR groups. TLF and major bleeding events showed similar trends. In patients undergoing PCI with third-generation DES, 3- to 6-month DAPT was comparable to 12-month DAPT for clinical outcomes regardless of renal function.