Incidence Of Major Bleeding Research Articles

Major Bleeding and Mortality After Revascularization of Left Main Disease

BackgroundThe incidence and prognostic impact of major bleeding (MB) after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for left main coronary artery disease (LMCAD) are unknown. ObjectivesThe goal of this study was to investigate the rates and outcomes of MB after LMCAD revascularization. MethodsIn the EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization) trial, 1,905 patients with unprotected LMCAD were randomized to undergo PCI (n = 948) or CABG (n = 957) and followed up for 5 years. MB was defined as TIMI major or minor bleeding, BARC (Bleeding Academic Research Consortium) types 3 to 5 bleeding, or any overt bleeding requiring blood transfusion. The association between MB and subsequent mortality was assessed in time-adjusted Cox regression models. ResultsAt 5 years, 217 patients (11.4%) had at least 1 MB event. Rates of 5-year MB were 7.9% after PCI vs 14.8% after CABG (OR: 0.48; 95% CI: 0.36-0.65; P < 0.0001). However, in-hospital MB was lower after PCI (3.8% vs 13.5%; OR: 0.25; 95% CI: 0.17-0.37), whereas postdischarge MB was lower after CABG (4.5% vs 2.0%; OR: 2.33; 95% CI: 1.33-3.09; Pinteraction < 0.0001). All 41 postdischarge MB events after PCI occurred in patients receiving dual antiplatelet therapy. MB events within 5 years were associated with a higher subsequent risk of all-cause mortality (adjusted HR: 2.71; 95% CI: 1.95-3.77; P < 0.0001), whether in-hospital or postdischarge (Pinteraction = 1.00) and after both PCI and CABG (Pinteraction = 0.95), driven both by increased cardiovascular and non-cardiovascular mortality. ConclusionsIn the EXCEL trial, CABG resulted in higher 5-year rates of all MB and in-hospital MB, although postdischarge MB was more frequent after PCI. MB after both procedures was associated with increased cardiovascular and noncardiovascular mortality within 5 years. (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization [EXCEL]; NCT01205776)

Safety and efficacy of intravenous recombinant human prourokinase for acute ischaemic stroke within 4·5 h after stroke onset (PROST-2): a phase 3, open-label, non-inferiority, randomised controlled trial

Intra-arterial prourokinase has been shown to be a promising thrombolytic agent in patients with acute ischaemic stroke. Given the global shortage of thrombolytics, we aimed to assess the non-inferiority of intravenous recombinant human prourokinase compared with alteplase in patients with acute ischaemic stroke who were ineligible for or who refused endovascular thrombectomy. PROST-2 was a phase 3, open-label, non-inferiority, randomised controlled trial conducted at 61 hospitals in China. Patients older than 18 years with acute ischaemic stroke, who were ineligible for or who refused endovascular thrombectomy, were randomly assigned in a 1:1 ratio within 4·5 h of stroke onset to receive intravenous recombinant human prourokinase (15 mg bolus followed by 20 mg infusion within 30 min) or intravenous alteplase (0·9 mg per kg, maximum dose 90 mg; 10% bolus followed by remainder as infusion over 60 min). The primary efficacy outcome was the proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days, assessed via masked review in the intention-to-treat population, with a non-inferiority margin for the risk ratio of 0·93. The primary safety outcome was the incidence of symptomatic intracranial haemorrhage within 36 h. This trial is registered with ClinicalTrials.gov (NCT05700591) and is now completed. Between Jan 29, 2023, and March 14, 2024, 1552 patients were randomly assigned: 775 received recombinant human prourokinase and 777 received alteplase. The primary outcome of a modified Rankin Scale score of 0 or 1 at 90 days was reached by 558 (72·0%) of 775 patients in the recombinant human prourokinase group versus 534 (68·7%) of 777 in the alteplase group (risk ratio 1·04 [95% CI 0·98 to 1·10]; p<0·0001 for non-inferiority). The frequency of symptomatic intracranial haemorrhage within 36 h was lower in the recombinant human prourokinase group than in the alteplase group (two [0·3%] of 770 patients vs ten [1·3%] of 775, risk difference -1·0 percentage points [95% CI -2·1 to -0·1]; p=0·021), as was the incidence of major bleeding at 7 days (four [0·5%] vs 16 [2·1%]; -1·5 percentage points (-2·8 to -0·4); p=0·0072). All-cause mortality within 7 days did not differ between groups (five [0·6%] deaths in the recombinant human prourokinase group vs 13 [1·7%] in the alteplase group; risk difference -1·0 percentage points; 95% CI -2·3 to 0·1]; p=0·060). In our trial, recombinant human prourokinase was shown to be non-inferior to alteplase for achieving excellent functional outcome, with no difference between groups in safety endpoints. These findings support the use of recombinant human prourokinase as a viable alternative to alteplase for patients with ischaemic stroke who are eligible for intravenous thrombolysis therapy but ineligible for or who have refused endovascular thrombectomy. Tasly Biopharmaceuticals, National Key R&D Program of China, National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Beijing Municipal Science & Technology Commission. For the Chinese translation of the abstract see Supplementary Materials section.

Safety of enoxaparin in patients implanted with continuous flow left ventricular assist devices.

The objective of this study is to determine the incidence of major bleeding events in patients implanted with continuous flow left ventricular assist devices (CF-LVADs) bridged with enoxaparin (LMWH) compared to intravenous unfractionated heparin (IV UFH) for a subtherapeutic INR on warfarin. A single-center, retrospective, cohort study was conducted including patients with CF-LVADs implanted between January 1, 2012 and July 1, 2020 who received at least one inpatient dose or outpatient prescription for LMWH or IV UFH at least 60 days after CF-LVAD implantation. The primary endpoint was the incidence of major bleeding. In total, 176 orders were screened and 90 orders in 62 unique patients were included. Major bleeding and thromboembolic events occurred in 1 (2.5%) versus 4 (10.0%) orders (p = 0.36) and 3 (7.5%) versus 1 (2.5%) orders (p = 0.62) in the LMWH and IV UFH groups, respectively. One patient had a fatal thromboembolic event in each group. More patients receiving IV UFH had minor bleeding events (10 [25.0%] vs. 3 [7.5%]; p = 0.03). There was no difference between bleeding and thromboembolic events in patients implanted with CF-LVADs prescribed LMWH or IV UFH for bridging of subtherapeutic INRs. Larger prospective randomized data are needed to validate these findings.

Device-Related Adverse Events and Flow Capacity of Percutaneous Ventricular Assist Devices.

Complication management is crucial in patients receiving mechanical circulatory devices. However, there are limited data on the association between the risks of complications and device type in patients with percutaneous ventricular assist devices (PVAD). The Japanese registry for PVAD (J-PVAD) is a nationwide ongoing registry that enrolls consecutive patients with cardiogenic shock treated with PVAD. We analyzed 5717 patients in the J-PVAD from February 1, 2020, to December 31, 2022, to compare the incident risks of device-related problems and all-cause mortality within 30 days after PVAD introduction based on flow capacities of first-line PVAD (low: Impella 2.5/CP, n=5375; high: Impella 5.0/5.5, n=342). The overall incidence of major device-related problems, including hemolysis, major bleeding, kidney injury, sepsis, and pump stop were 13%, 21%, 7%, 3%, and 1%, respectively. The all-cause mortality rate was 34%. The incident risks of hemolysis (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.24-0.58), kidney injury (HR 0.32, 95%CI 0.18-0.57), and pump stop (HR 0.38, 95%CI 0.16-0.91) were lower in patients with high-flow PVAD compared with those with low-flow PVAD. The risks of major bleeding or sepsis did not differ significantly between groups. The risk of all-cause mortality was lower in patients with high-flow PVAD compared with those with low-flow PVAD (HR 0.79, 95%CI 0.65-0.96). Compared with those with low-flow PVAD, patients with high-flow PVAD had lower incident risks of device-related problems, including hemolysis, kidney injury, and pump stop, as well as lower risk of all-cause mortality.

Abstract 4136632: Impact of Postoperative Atrial Fibrillation on Long-term Clinical Outcomes in Patients after Coronary Artery Bypass Grafting

Background: The impact of postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) on long-term clinical outcomes has not been adequately evaluated yet. Methods: Among consecutive 14927 patients who underwent their first coronary revascularization in the CREDO-Kyoto PCI/CABG Registry Cohort-3 (2011-2013), the study population consisted of 1483 patients who underwent CABG after excluding those with prior AF. POAF was defined as newly documented AF during hospitalization for CABG. The primary outcome measure was all-cause death after discharge. The median clinical follow-up was 5.7 (interquartile range, 4.4-6.6) years. Results: POAF was observed in 337 patients (23%). Multivariable logistic regression analysis indicated that age &gt;=75 years (odds ratio [OR], 1.61; 95% confidence interval [CI], 1.24-2.10; P&lt;0.001) and cardiopulmonary bypass (CPB) use (OR, 1.40; 95%CI, 1.09-1.79; P=0.01) were independent predictors of POAF. Of the 1400 patients discharged alive among the study population, the POAF group included more older patients, patients with prior stroke, and patients prescribed beta-blockers and oral anticoagulants than the non-POAF group. The cumulative 5-year incidence of all-cause death was 15.9% in the POAF group and 13.0% in the non-POAF group (Log-rank P=0.38). After adjusting for confounders, the adjusted risk for all-cause death was almost neutral (adjusted HR, 0.96; 95%CI, 0.70-1.31; P=0.81). The cumulative 5-year incidence of stroke was significantly higher in the POAF group than in the non-POAF group (8.0% versus 4.2%; Log-rank P=0.02), and the adjusted risk of stroke in the POAF group relative to the non-POAF group tended to be higher (adjusted HR: 1.58, 95%CI, 0.99-2.53; P=0.057). However, the cumulative 5-year incidence of major bleeding was significantly higher in the POAF group than in the non-POAF group (14.6% versus 10.7%; Log-rank P=0.01). Even after adjusting for confounders, the excess risk of major bleeding in the POAF group was significant (adjusted HR, 1.42; 95%CI, 1.01-2.00; P=0.041). Conclusions: Advanced age and CPB use were associated with POAF occurrence. POAF was not associated with long-term mortality after discharge. However, it tended to be associated with a higher risk for stroke and was associated with a significantly higher risk for major bleeding. Further study would be needed to clarify the appropriate management of POAF after CABG.

Real-world data on direct oral anticoagulants in BCR::ABL1-negative myeloproliferative neoplasms (MPNs): a multicenter retrospective study on behalf of scientific subcommittee on MPNs for Turkish society of hematology.

BCR::ABL1-negative myeloproliferative neoplasms (MPNs) pose a substantial risk of thrombosis, leading to significant morbidity and mortality. Anticoagulant therapy, historically based on vitamin K antagonists (VKAs), has limitations in preventing recurrent thrombotic events and managing bleeding complications. Direct oral anticoagulants (DOACs) offer a potential alternative with improved pharmacokinetics and compliance. However, evidence on DOAC efficacy and safety in MPNs remains limited, necessitating further investigation. In this multicenter retrospective study in Türkiye, we assessed real-world usage patterns and outcomes of DOACs in MPN patients. Data from 220 patients with PV, ET, or PMF receiving DOACs or VKAs for thrombosis or nonvalvular atrial fibrillation (NVAF) were collected from medical records. Thrombotic events and bleeding episodes were documented based on ISTH criteria. DOACs were used in 126 patients as first-line anticoagulant therapy or following VKAs. Ninety-four patients were on VKAs, of which 83 as a first-line treatment. There were eight thromboses (6.3%) seen in 126 DOAC patients, and similarly, seven episodes (9.4%) of thrombosis were observed in 94 patients using VKA. Major bleeding occurred in seven patients (5.6%) on DOAC and 3 (3.2%) in VKA. Thrombotic and bleeding risks were comparable between DOACs and VKAs (p = 0.708 and p = 0.158, respectively). The incidence rate of thrombosis in the VKA group is 1.1% and in the DOAC group is 1.9%. The incidence of major bleeding in the VKA group is 0.6% and 1.6% in the DOAC group. To the best of our knowledge, our study included the largest number of MPN patients to date, comparing DOACs with VKA in terms of both efficacy and safety, which suggests DOACs as promising alternatives to VKAs for managing thrombotic risk in MPNs with manageable toxicity. Despite the limitations of retrospective studies, DOACs' benefits in terms of efficacy and compliance warrant further investigation through prospective trials. Individualized treatment decisions should consider patient-specific factors, emphasizing collaborative efforts between specialists to optimize DOAC therapy in patients with MPNs. Comparable efficacy and safety between DOACs and VKAs were observed in MPN patients.

Clinical characteristics and short-term outcomes of patients with critical acute pulmonary embolism requiring extracorporeal membrane oxygenation: from the COMMAND VTE Registry-2

BackgroundExtracorporeal membrane oxygenation (ECMO) might be required as a treatment option in patients with critical pulmonary embolism (PE). However, the clinical features and outcomes of the use of ECMO for critical acute PE are still limited. The present study aimed to clarify the clinical characteristics, management strategies and outcomes of patients with acute PE requiring ECMO in the current era using data from a large-scale observational database.MethodsWe analyzed the data of the COMMAND VTE Registry-2: a physician-initiated, multicenter, retrospective cohort study enrolling consecutive patients with acute symptomatic venous thromboembolism (VTE). Among 2035 patients with acute symptomatic PE, there were 76 patients (3.7%) requiring ECMO.ResultsOverall, the mean age was 58.4 years, and 34 patients (44.7%) were men. Cardiac arrest or circulatory collapse at diagnosis was reported in 67 patients (88.2%). The 30-day incidence of all-cause death was 30.3%, which were all PE-related deaths. The 30-day incidence of major bleeding was 54.0%, and the vast majority of bleedings were procedure site-related bleeding events and surgery-related bleeding (22.4%). The 30-day incidence of all-cause death was 6.3% in 16 patients with surgical intervention, 43.8% in 16 patients with catheter intervention, 25.0% in 16 patients with thrombolytic therapy, and 39.3% in 28 patients with anticoagulation only.ConclusionsThe current large real-world VTE registry in Japan revealed clinical features and outcomes of critical acute PE requiring ECMO in the current era, which suggested several unmet needs for future clinical trials.

Safety and efficacy of catheter-directed thrombectomy without thrombolysis in acute pulmonary embolism: A systematic review and meta-analysis

BackgroundThis meta-analysis aims to investigate the safety and efficacy of catheter-directed thrombectomy (CDT) without using adjunct thrombolysis as reperfusion therapy to manage intermediate and high-risk pulmonary embolism (PE). MethodsA literature search of Ovid MEDLINE, Embase, CiNAHL, Cochrane Library, and Web of Science was conducted from inception to January 2024. Eligible studies reported more than 10 patients treated for acute PE with catheter-directed thrombectomy only, who were over 18 years of age. Primary endpoints were major bleeding, in-hospital mortality, and hemodynamic changes. ResultsEighteen studies (n = 803) were included for quantitative analysis. The pooled estimate of incidences of in-hospital mortality and major bleeding was 1.8 % (95 % CI 0.009, 0.027) and 2.1 % (95 % CI 0.011, 0.031) respectively. A pooled estimate reported a post-procedural increase in oxygen saturation and systolic blood pressure by 8.96 % (95 % CI: 3.54, 14.38) and 15.02 mmHg (95 % CI 6.35, 23.69) respectively. Post-procedural mean pulmonary artery pressure, right ventricle/left ventricle (RV/LV) ratio, and Miller score were reduced by 10.30 mmHg (95 % CI -14.94, −5.66), 0.29 (95 % CI -0.50, −0.08) and 8.09 (95 % CI -10.70, −5.47) respectively. ConclusionCDT without adjunctive thrombolysis may lead to improvements in hemodynamic outcomes and appears to exhibit favorable safety profiles. This meta-analysis provides a rationale for further research comparing CDT alone against using adjunct thrombolysis to determine optimal management strategies for intermediate to high-risk acute PE.

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.

The efficacy and safety of thrombolytic therapy for acute pulmonary embolism in patients with active malignant disease

Abstract Background Active malignant disease is associated with pulmonary embolism and the treatment of this condition is very challenging. The efficacy and safety of thrombolytic therapy for acute severe PE in patients with active malignant disease is unknown. Aim This study aimed to investigate hospital mortality rate and the incidence of major bleeding at 7 days according to the International Society of Thrombosis and Hemostasis (ISTH) criteria in patients with active malignant disease who were treated with thrombolytic therapy due to severe acute PE. Methods Patients with acute PE proven by computed tomography pulmonary angiography who were admitted to intensive care units have enrolled in the Regional PE Registry (REPER) since 2015, consisting of 10 hospitals from the 4 east Balkan countries. The decision to use thrombolytic therapy was at the discretion of the attending physicians, and it was used in high-risk, and intermediate-high-risk PE patients. Hospital mortality and the incidence of major bleeding at 7 days were compared between patients with active cancer and those without it who received thrombolytic therapy. Alteplase-based therapy was used. Results Among 2070 patients with acute PE enrolled in REPER, intermediate-high and high-risk PE had 795 patients without malignant disease and 135 had active malignant disease in the last 6 months. Patients with malignant disease had less chance to be treated with thrombolysis than patients without it (29.1% vs 44.7%, OR 0.508, 95%CI 0.341-0.756, p=0.001). For patients treated with thrombolysis, hospital mortality was non significantly higher in patients with the malignant disease compared to patients without it (25.6% vs 16,1%, OR 1.803, 95%CI 0.833-3.904, p=0.132), and the incidence of major bleeding at seven days was similar (15.4% vs 18.5%, OR 0.800, 95%CI 0.322-1.989, p=0.6131). There was no significant difference in age, sex, and PE risk distribution between patients with active malignant disease and those without it who were treated with thrombolysis. Conclusion Thrombolytic therapy seems to be underutilized in patients with the active malignant disease compared to patients without it in severe acute PE. In the selected patients who were treated with thrombolysis for severe acute PE, the efficacy and safety are similar between patients with and without active malignant disease.

Major bleeding complications and antithrombotic treatment after isolated surgical bioprosthetic aortic valve replacement

Abstract Background Despite advancements in surgical techniques and perioperative care, post-operative bleeds and stroke remain significant concerns after bioprosthetic surgical aortic valve replacement (SAVR). Purpose We assessed the incidence of short-term (30d) and long-term major bleeds and strokes and their relations to antithrombotic treatment after isolated bioprosthetic SAVR. Methods The CAREAVR study included 721 patients who underwent isolated SAVR at four Finnish university hospitals between 2002 and 2014. The day-to-day information on short-term antithrombotic treatment was available from a subgroup including 227 patients, of whom 138 (60.7%) had preoperative aspirin. Preoperative aspirin was usually discontinued the day before the index surgery. Enoxaparin 1mg/kg twice daily and vitamin K antagonist (VKA) were routinely initiated on the first postoperative day, and enoxaparin continued until the INR remained at a therapeutic level ≥ 2.0 for two days. The routine duration of VKA treatment after surgery was 3 months. Results The median follow-up time was 4.9 (interquartile range 3.0–7.0) years. During the short-term 30-day period, 31 (4.3%) patients had a major bleed, and 13 (1.8%) patients experienced a major stroke. A vast majority of the bleeding (80.6%) occurred within two days after the surgery, and the tail effect of preoperative aspirin (5-7d) was present in 51.6% of episodes, indicating unintentional triple antithrombotic therapy. During the long-term follow-up (&amp;gt;30d after the index surgery), 40 (5.5%) major bleeding episodes occurred, and 47 (6.5%) patients experienced a major stroke. Overall, 23 (57.5%) of the patients with major bleeding were on OAC during the event. In addition, 13 (27.7%) of the patients experiencing major stroke during the long-term follow-up were on OAC during the event. Conclusions Compared to major strokes, the incidence of perioperative major bleeds was over twofold, the majority occurring during the tail effect of preoperative aspirin. During the long-term follow-up, the risks of stroke and bleeding were equal, and the majority of bleeding episodes appeared during anticoagulation treatment.

Short vs Standard Duration Dual Antiplatelet Therapy after Percutaneous Coronary Intervention with New-Generation Drug-Eluting Stents: A Meta- Analysis

Objective: In patients with coronary artery disease, dual antiplatelet therapy (DAPT) is recommended after percutaneous coronaryintervention, but the duration is still debated. This meta-analysis compared short-duration (1 to 3 months) to standard-time (twelve months) double antiplatelet treatment in patients who received coronary intervention with new generation drug eluting Stent.Methodology: To conduct this examination, we methodically looked at PubMed, Cochrane CENTRAL, Embase, and Web of Sciencedatabases for randomized controlled trials, evaluating varying durations of double antiplatelet treatment following new generation stents implantation from July to September 2023. Seven randomized controlled trials were included with a total of 22,945 patients. The primary efficacy endpoint was the incidence of Major adverse cardiovascular events, such as cardiac mortality, heart attack, stent coagulation, and target vessel revascularization; while the safety endpoint was the incidence major bleeding. Secondary endpoints were major adverse cardiovascular and cerebro-vascular complications, any bleeding, and net adverse cardiovascular incidence for a year after stent implantation.Results: Short-time DAPT was linked to a significantly less incidence of major bleeding (0.8% vs 1.5%), any bleeding (2.5% vs 4.2%)and NACE (2.5% vs 4.2%) compared to standard duration of DAPT. No significant variation was noticed among the two groups regarding major adverse cardiovascular events (4.1% vs. 4.2%) and acute cardiovascular and cerebrovascular incidents (4.7% vs. 4.8%). Short-duration DAPT in patients with acute coronary syndrome was linked with decreased risk of bleeding and net adverse cardiovascular events.Conclusion: Short-duration DAPT significantly lowers bleeding risk and reduces net clinical adverse events without increasing ischemic risk, making it a reasonable choice for people with new-generation drug eluting stents, particularly those with highbleeding risk or recent surgery.

Elective endovascular reperfusion therapies in intermediate-high risk pulmonary embolism after PERT assesment

Abstract Background The ideal management of patients with intermediate-high risk (IHR) pulmonary embolism (PE) is still unknown. A multidisciplinary approach by Pulmonary Embolism Response Teams (PERT) in combination with the advent of endovascular therapies sounds promising. Purpose Evaluate in-hospital events of elective endovascular reperfussion therapies in selected IHR PE patients after PERT assesment in a single center initial experience. Methods Analysis of consecutive patients with PE admitted from Jan/2017 to Jan/2024. The in-hospital evolution of an elective invasive strategy defined by an institutional PERT (since April/2021) in IHR PE patients was compared against the current standard of care (isolated anticoagulation and reperfusion only after hemodynamic collapse). Patients with limitations of therapeutic efforts due to comorbidities were excluded. Results 361 patients with PE were treated with 76 (21.1%) stratified as IHR. After excluding 14 patients due to limitations of therapeutic efforts (78±9.4 years; 64.3% active cancer), 62 were included for analysis. An elective endovascular treatment was performed in 20 (31.3%) patients; these were younger and with fewer comorbidities. However, they had more tachypnea, greater central distribution of thrombotic burden and signs of right ventricle overload assessed by flattening of the interventricular septum. Baseline characteristics, clinical presentation and management are described in table 1. Within the invasive group, endovascular reperfusion was performed with local thrombolysis (70%), aspiration thrombectomy (15%) or their combination (15%). During hemodynamic evaluation, hidden shock was detected in 42.9% (6/14), with improvements in cardiac index observed after reperfusion therapy (n=8; 2.1 vs. 2.5). Improvement was also observed in pulmonary artery systolic pressure (n=14, 56.9 vs. 37.1mmHg; p&amp;lt;0.001) and right ventricular function (n=15, TAPSE 16 vs. 22mm; p&amp;lt;0.001). Compared with the current standard of care, an elective invasive approach was associated with a shorter hospital stay (6.5 vs. 9 days; p=0.02), less hemodynamic collapse (0% vs. 19.1%; p=0.04), need for mechanical ventilation (0% vs. 19.1%; p=0.04) and in-hospital mortality (0% vs. 21.4%; p=0.04) without differences in the incidence of major bleeding (Fig 1). After multivariate logistic regression analysis, the mortality benefit persisted in favor of an invasive strategy (p=0.014). Conclusions An "elective" invasive strategy in selected patients with IHR PE after PERT assessment was safe and resulted in less major in-hospital cardiovascular events in a single-center initial experience. Although these results should be taken with caution given the limitations of this study (single-center, small observational sample), they are in line with recent reports and are the focus of ongoing large randomized clinical trials.Table 1

The association between steroid use and recurrent venous thromboembolism: from the COMMAND VTE Registry-2

Abstract Background It is well known that use of oral steroids is a risk factor for development of venous thromboembolism (VTE). However, the impact of use of oral steroids on VTE recurrence has not been fully evaluated in the era of direct oral anticoagulants (DOAC), which has been a clinically relevant issue in the decision-making of anticoagulation strategies for patients who need oral steroids after VTE diagnosis. Purpose We aimed to investigate long-term clinical outcomes in VTE patients treated with oral steroids after VTE diagnosis in the DOAC era. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The current study population were divided into 2 groups according to the use of oral steroids after VTE diagnosis; the steroid group and the non-steroid group. We compared clinical characteristics, management strategies, and outcomes including recurrent VTE, major bleeding and all-cause death, between the 2 groups. Results Patients with steroids and those without accounted for 693 (13%) and 4,504 (87%), respectively. Patients with steroids more often had chronic kidney disease (29% vs. 18%, P&amp;lt;0.001), autoimmune disease (50% vs. 5.4%, P&amp;lt;0.001), thrombocytopenia (7.7% vs 4.9%, P=0.002), and anemia (64.4% vs 54.1%, P&amp;lt;0.001), whereas there was no significant difference in the mean age (68.5 vs. 67.6 years old, P=0.16), the prevalence of women (62% vs 58%, P=0.06), active cancer (30% vs. 29%, P=0.42), and history of VTE (8.4% vs 6.8%, P=0.12) between the 2 groups. The cumulative 5-year incidence of discontinuation of anticoagulation therapy were not significantly different between the 2 groups (61.5% vs. 58.5%, log-rank P=0.16). The cumulative 5-year incidences of recurrent VTE nor major bleeding were not significantly different between the 2 groups (10.4% vs. 9.4%, log-rank P=0.55; 16.9% vs. 13.3%, log-rank P=0.16, respectively). Even after adjusting confounders, the risks of recurrent VTE nor major bleeding were not significantly different (adjusted hazard ratio = 0.97, 95% confidence interval = 0.65-1.45, P = 0.89; adjusted hazard ratio = 1.12, 95% confidence interval = 0.84-1.50, P = 0.44). The cumulative 5-year incidences of all-cause death was significantly different between the 2 groups (44.2% vs. 30.2%, log-rank P&amp;lt;0.001). Even after adjusting confounders, the risk of all-cause death remained significantly different (adjusted hazard ratio = 1.82, 95% confidence interval = 1.56-2.12, P&amp;lt;0.001). Conclusions Use of oral steroids after VTE diagnosis was not significantly associated with an increased risk of VTE recurrence in the DOAC Era, which might suggest that there could be no major concerns on an increased risk of recurrent VTE with oral steroids after VTE diagnosis under appropriate anticoagulation therapy.

Effect of the longitudinal change in anemia status on clinical outcomes for patients with nonvalvular atrial fibrillation: analysis from the Hokuriku-Plus AF registry

Abstract Background Anemia is a common comorbidity in older patients with heart failure (HF)1 and atrial fibrillation (AF)2, associated with an increased risk of adverse events. This study evaluated the prognostic effects of longitudinal changes in anemia status on clinical outcomes in patients with AF, as limited data are available on this aspect. Methods and Results We prospectively evaluated data of 1,388 patients with AF obtained from the Hokuriku-Plus AF registry (1,010 men, 72.3±9.7 years) and recorded the incidence of cardiovascular death (CVD), HF, thromboembolism, and major bleeding. Finally, 1,233 patients with AF with baseline and first year of follow up hemoglobin levels were evaluated. Patients were categorized into 3 groups based on the longitudinal changes in 1-year anemia status: AF without anemia (group 1), AF with improved anemia (group 2), and AF with sustained or new-onset anemia (group 3). During 1–5-year follow up, the incidences of CVD, HF, thromboembolism, and major bleeding were significantly higher in patients with AF and anemia than in those without (Figure1). Additionally, the incidence of CVD or HF was significantly higher in group 3 than in groups 1 and 2 (Figure 2). Multivariate analysis revealed no anemia or improvement from anemia in 1 year as an independent predictor for reducing CVD and HF. Conclusions Recovery from anemia may be associated with a favorable clinical course in AF.

Clinical outcomes of edoxaban treatment without parenteral anticoagulation therapy for acute venous thromboembolism: Insight from the COMMAND VTE Registry-2

Abstract Background Direct oral anticoagulants (DOACs) including edoxaban are currently widely used all over the world. Each DOAC has a specific usage for the treatment and second prevention of venous thromboembolism (VTE) in the acute phase as well as in the chronic phase. Edoxaban is recommended to be administered after an appropriate initial treatment including parenteral anticoagulation therapy such as heparin. However, because of the rapid anticoagulant effect of edoxaban after oral intake, some physicians could administer edoxaban initially without parenteral anticoagulation therapy in the daily clinical practice, which has not been investigated so far. Purpose The purpose of this study is to explore the effectiveness and safety of edoxaban treatment for VTE without initial parenteral anticoagulation therapy. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. Of those, 1842 patients received edoxaban including 848 patients with pulmonary embolism (PE) and 994 patients with deep vein thrombosis (DVT) alone, who were divided into 2 groups based on the presence or absence of initial parenteral anticoagulation therapy with heparin. Propensity score matching (PSM) was performed to adjust for potential baseline differences in the 2 groups. Results PE and DVT patients with initial parenteral anticoagulation therapy with heparin accounted for 623 (73.5%) and 244 (24.5%), respectively. After the PSM, 195 pairs of PE patients and 226 pairs of DVT patients were matched. In PE patients, those matched by the PSM were relatively mild cases compared to the unmatched cases (simplified PESI score=0: 25.9% vs. 12.4%, P&amp;lt;0.001). Whereas, in DVT patients, those matched were relatively severe cases compared to unmatched cases (isolated distal DVT: 24.1% vs. 71.0%, P&amp;lt;0.001). In the matched cohort, there was no significant difference in baseline characteristics between the 2 groups, including simplified PESI score in PE patients and thrombus location profile in DVT patients. In both PE patients and DVT patients, the 30-day cumulative incidences of all-cause death were not significantly different between the 2 groups (PE patients: 3.7% vs. 2.6%, P=0.56; DVT patients: 2.7% vs. 4.5%, P=0.31). Similarly, the 30-day cumulative incidences of recurrent VTE and major bleeding were not significantly different between the 2 groups (recurrent VTE: PE patients: 0% vs. 0.5%, P=0.32; DVT patients: 0.6% vs. 0.9%, P=0.99; major bleeding: PE patients: 1.5% vs. 3.2%, P=0.32; DVT patients: 2.2% vs. 3.2%, P=0.54) Conclusion In this current real-world VTE registry, a certain number of patients received edoxaban without parenteral anticoagulation therapy, who did not show a signal of worse clinical outcomes.

Application of DOAC Score for the risk-stratification of major bleeding in patients with venous thromboembolism on direct oral anticoagulants: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction Bleeding complications are still a major concern in anticoagulation therapy for venous thromboembolism (VTE), even in the direct oral anticoagulant (DOAC) era. Thus, the risk stratification of bleeding during anticoagulation therapy is essential, although most of currently available bleeding risk scores have been developed from patients receiving vitamin K antagonists, which could have limited validity in those receiving DOACs. Very recently, the DOAC Score has been developed to predict major bleeding in patients with atrial fibrillation on DOACs; however, the score has not yet been validated in patients with VTE. Purpose The present study aimed to evaluate the usefulness of the DOAC Score in patients with VTE, using a large-scale multicenter observational database of patients with VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 3539 patients with VTE who received DOACs and had a calculated DOAC Score. The eligible patients were classified into 5 risk categories: very low (score 0–3), low (score 4–5), moderate (6–7), high (score 8–9), and very high (score ≥10). We used the Kaplan-Meier method to estimate the cumulative incidence and assessed the discriminatory ability of the DOAC Score for major bleeding at 1 year by calculating the area under the receiver operating characteristic curve. We also assessed the discriminatory ability of the VTE-BLEED and RIETE scores. Results In the present study population, the very low-risk group accounted for 1437 patients (41%), low-risk group for 828 (23%), moderate-risk group for 812 (23%), high-risk group for 326 (9.2%), and very high-risk group for 136 (3.8%). The proportion of anemia was highest in the very high-risk group (71%) and lowest in the very low-risk group (47%). The prevalence of active cancer was highest in the low-risk group (36%) and lowest in the very high-risk group (18%). During the first year of anticoagulation therapy, major bleeding occurred in 180 patients. The cumulative 1-year incidence of major bleeding seemed to be different according to the 5 groups, but the risks could not be well-stratified (Figure 1). The discriminating power of the DOAC Score was relatively low with a C-statistic of 0.52 (95% CI, 0.48–0.57) (Figure 2), while those of VTE-BLEED and RIETE scores were modest with C-statistics of 0.66 (95% CI, 0.60–0.73) and 0.67 (95% CI, 0.64–0.71), respectively. Conclusions The risk of 1-year major bleeding on DOACs in patients with VTE was not well-stratified according to the risk categories by the DOAC Score, which might suggest that patients with VTE have different risk factors for bleeding on DOACs as compared to those with atrial fibrillation. A new bleeding risk score for DOAC specifically in patients with VTE would be warranted in the future.Figure 1Figure 2

Antithrombotic strategies after cryptogenic stroke: a systematic review, pairwise, and network meta-analysis of randomized controlled trials

Abstract Background No definite etiology is identified in 30-40% of ischemic stroke cases, which is known as cryptogenic stroke. Several antithrombotic strategies have been investigated for cryptogenic stroke management; however, the optimal strategy remains unknown. Purpose We aim to assess the efficacy and safety of oral anticoagulants (OACs) versus aspirin, and the comparative efficacy and safety of different OACs after cryptogenic stroke. Methods A systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until February 2024. We used the fixed-effects model to report dichotomous outcomes using a risk ratio (RR), with a 95% confidence interval (CI). Analysis was conducted using R, version 4.2.0. Results Seven RCTs with 15.240 patients were included. In pairwise analysis, there was no difference between OACs and aspirin regarding all-cause mortality (RR: 1.13, CI [0.89, 1.43], P= 0.33) and stroke recurrence (RR: 0.93, CI [0.82, 1.07], P= 0.31). However, OACs were associated with a significantly increased incidence of major bleeding (RR: 1.6, CI [1.24, 2.05], P= 0.01), with no difference regarding the incidence of intracranial hemorrhage (RR: 1.09, CI [0.3, 3.97], P= 0.9). Moreover, in network analysis, none of the OACs showed a significant efficacy in preventing all-cause mortality and stroke recurrence compared to aspirin. However, only rivaroxaban significantly increased the incidence of major bleeding (RR: 2.69, CI [1.67, 4.33]). Conclusion OACs did not protect against stroke recurrence or decrease the incidence of all-cause mortality but increased the incidence of major bleeding in patients with cryptogenic stroke.

The influence of concomitant antiplatelet therapy in venous thromboembolism patients treated with anticoagulants in the DOAC era: insight from the COMMAND VTE Registry-2

Abstract Background/Introduction The mainstay of treatment and second prevention of venous thromboembolism (VTE) is anticoagulation therapy, and recently direct oral anticoagulant (DOAC) for VTE have prevailed all over the world as oral anticoagulation therapy. Although concomitant antiplatelet therapy in addition to oral anticoagulation therapy could have an influence on both recurrent VTE and bleeding events, there have been still limited real-world data on the issue in the DOAC era. Purpose We aimed to investigate long-term clinical outcomes in VTE patients treated with concomitant antiplatelet therapy in the DOAC era. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. After excluding 407 patients without oral anticoagulation therapy, the current study population was consisted of 4790 VTE patients with oral anticoagulation therapy, who were divided into 374 patients (7.8%) treated with concomitant antiplatelet therapy and 4416 patients (92.2%) treated with only oral anticoagulation therapy. Results Patients with concomitant antiplatelet therapy were older (Concomitant antiplatelet therapy: 74.1 vs. Only oral anticoagulation therapy: 67.3 years, P&amp;lt;0.001), were less often women (52% vs 59%, P=0.005) and more frequently had history of major bleeding (9.8% vs 6.0%, P=0.003), myocardial infarction (16% vs 0.9%, P&amp;lt;0.001) and stroke (33% vs 6.8%, P&amp;lt;0.001). The cumulative incidences of recurrent VTE were not significantly different between the 2 groups (5.9% vs 9.6% at 5-year, Log rank P=0.06). Similarly, the cumulative incidences of major bleeding (14.6% vs 13.3% at 5-year, Log rank P=0.11) and stroke (8.3% vs 6.0% at 5-year, Log rank P=0.12) were not significantly different between 2 groups. However, the cumulative incidences of clinically relevant all bleeding (29.0% and 23.0% at 5-year, Log rank P=0.007) were significantly higher in concomitant antiplatelet therapy group, which was statistically significant even after adjusting confounders. Conclusion In the current large VTE registry in the DOAC era, concomitant antiplatelet therapy in addition to oral anticoagulation therapy for patients with VTE was not significantly associated with the risks recurrent VTE, major bleeding or stroke, but was associated with an increased risk of clinically relevant all bleeding.Study Flow ChartMain results

Evaluation of Pharmaco-invasive PCI in Terms of in Hospital Clinical Outcome of Acute Anterior ST Segment Elevation Myocardial Infarction Patients Compared to Primary PCI

Background: The strategic reperfusion early after Myocardial Infarction trial and the French Registry of Acute Anterior ST segment elevation MI suggested that pharmaco-invasive strategy compares favorably with primary percutaneous coronary intervention (PPCI). Objectives: To evaluate in hospital clinical outcome of patients with acute anterior ST segment elevation myocardial infarction undergoing Primary PCI and pharmaco-invasive PCI. Methods: This cross sectional study was conducted in United Hospital, Dhaka. A total of 120 patients were studied. These patients were categorized into two groups. Those with acute anterior ST segment elevation MI who underwent primary PCI was denoted as group A (n= 55) and those with acute anterior ST segment elevation thrombolysed by streptokinase followed by PCI confined to pharmaco-invasive PCI was denoted as group B (n=65). Results: Acute LVF was more in pharmaco-invasive group than in primary PCI group and was statistically significant (p= 0.032). 02 patients (3.6%) died in primary PCI group: one of which was due to ventricular fibrillation followed by asystole 3 hours after procedure and the other died due to cardiac arrest 10 hours after the procedure. No major bleeding incidence was found in both groups. Conclusion: Acute anterior ST segment elevation myocardial infarction patients receiving pharmaco-invasive treatment compared with the Primary PCI had higher incidence of acute LVF and no significant discrepancy was observed regarding bleeding events, death, stent thrombosis, arrythymia, heart block and cardiac arrest. J Shaheed Suhrawardy Med Coll 2023; 15(1): 34-38