Incidence Of Major Bleeding Research Articles

Anticoagulation strategies and long-term recurrence in patients with venous thromboembolism in the era of direct oral anticoagulants

BackgroundThere has been limited data on anticoagulation strategies and long-term recurrence in patients with venous thromboembolism (VTE) in the era of direct oral anticoagulant (DOAC). MethodsThe COMMAND VTE Registry-2 is a multicenter retrospective cohort study enrolling 5197 consecutive patients with acute symptomatic VTE between January 2015 and August 2020 among 31 centers in Japan. In this primary report, the entire cohort was divided into 5 groups; major transient risk factors (N = 475, 9.1%), minor transient risk factors (N = 788, 15%), unprovoked (N = 1913, 37%), non-malignant persistent risk factors (N = 514, 9.9%), and active cancer (N = 1507, 29%) groups. ResultsDOACs were administered in 79% of patients who received oral anticoagulants. Discontinuation of anticoagulant at 1 year was most frequent in the major transient risk factors group (57.2%, 46.3%, 29.1%, 32.0%, and 45.6%). The cumulative 5-year incidence of recurrent VTE was lowest in the major transient risk factors group (2.6%, 6.4%, 11.0%, 12.1%, and 10.1%, P < 0.001). The cumulative 5-year incidence of major bleeding was highest in the active cancer group (9.8%, 11.4%, 11.0%, 15.5%, and 20.4%, P < 0.001). After discontinuation of anticoagulation therapy, the cumulative 5-year incidence of recurrent VTE was highest in the unprovoked group (3.3%, 11.0%, 24.9%, 17.5%, and 11.8%, P < 0.001). ConclusionsIn this large real-world VTE registry, anticoagulation strategies and long-term recurrence widely differed depending on the baseline characteristics. Detailed risk stratifications of recurrent VTE could be useful for decision-making of anticoagulation strategies, whereas the bleeding-risk assessment might be especially important in the era of DOAC. Clinical Trial RegistrationURL: http://www.umin.ac.jp/ctr/index.htm Unique identifier: UMIN000044816.

Comparison of outcomes of self-expanding versus balloon-expandable valves for transcatheter aortic valve replacement: a meta-analysis of randomized and propensity-matched studies

BackgroundThe postoperative outcomes of transcatheter aortic valve replacement (TAVR) with the new generation of self-expanding valves (SEV) and balloon-expandable valves (BEV) remain uncertain.MethodsWe conducted a meta-analysis based on randomized controlled trials (RCTs) and propensity score-matched (PSM) studies to evaluate the performance of the new generation TAVR devices, with a focus on Edwards SAPIEN 3/Ultra BEV, Medtronic Evolut R/PRO SEV, and Boston ACURATE neo SEV. Our primary endpoints were mortality and complications at both 30 days and one year post-operation.ResultsA total of 4 RCTs and 14 PSM studies were included. Our findings showed no significant difference between SEV and BEV regarding 30-day and 1-year mortality rates. ACURATE SEV required less permanent pacemaker implantation (PPI) at 30-day as compared to SAPIEN BEV, while Evolut SEV required a higher rate of PPI than SAPIEN BEV. The incidence of stroke, major or life-threatening bleeding (MLTB), major vascular complications (MVC), coronary artery obstruction (CAO) and acute kidney injury (AKI) did not differ significantly between the two groups. SEV had a larger effective orifice area (EOA) and lower mean transvalvular gradients (MPG) compared to BEV. However, there was an increased risk of paravalvular leakage (PVL) associated with SEV.ConclusionsIn terms of 30-day mortality, stroke, bleeding, MVC, AKI, CAO, and one-year mortality, there was comparability between the two valve types following TAVR. SEV was associated with better hemodynamic outcomes, except for a higher incidence of PVL. Compared to SAPIEN BEV, ACURATE SEV had a lower risk of PPI at 30 days, while Evolut SEV was associated with a higher risk of PPI. These findings underscore the importance of personalized valve selection.

Comparison of Various Regimens of Antithrombotic Therapy in Patients With Valvular Heart Disease and Coronary Artery Disease After Surgical and Interventional Interventions

To evaluate the postoperative incidence of bleeding, incidence of thromboembolic complications, and all-cause mortality in patients with valvular heart disease and ischemic heart disease (IHD) associated with various regimens of the antithrombotic treatment during one year after surgery. This study included 271 patients with valvular heart disease and IHD after heart valve replacement and myocardial revascularization from 2009 through 2018. However, during the follow-up period (12 months), contact with 12 patients was lost, and therefore these patients were excluded from the study. Further analysis included 259 patients. Coronary artery bypass grafting (CABG) in combination with heart valve intervention was performed in 217 (83.8 %) patients, and percutaneous coronary interventions (PCIs) were performed in 42 (16.2 %) patients. There were 197 (72.7 %) male participants; median age was 64.0 [58.0; 67.5] years. The patients were divided into two groups. Group 1 consisted of 113 patients who received postoperative dual antithrombotic therapy (DAT) with acetylsalicylic acid (ASA)/clopidogrel+vitamin K antagonist (VKA). Group 2 included 146 patients receiving postoperative triple antithrombotic therapy (TAT) with ASA+clopidogrel+VKA. Follow-up duration was 12 months after surgery. Due to significant intergroup differences in major clinical anamnestic data, the data were adjusted using pseudo-randomization (Propensity Score Matching, PSM). In result, 109 patients were selected for each group. The incidence of adverse hemorrhagic outcomes was significantly higher in the group treated with TAT than with DAT. Minor bleedings were observed in 19 (17.4 %) vs. 8 (7.3 %) cases; moderate, clinically significant bleedings in 16 (14.7 %) vs. 6 (5.5 %) cases; and the total number of bleedings was 35 (32.1 %) vs. 14 (12.8 %; p=0.02, p=0.02, and р=0.001, respectively). Comparing the incidence of major bleedings did not show and significant intergroup differences (p=1.000). The incidence rate of any bleeding during the follow-up period was 32.1 % in patients treated with TAT (n=109) and 12.8 % in patients treated with DAT (n=109; p=0.005). The incidence of no bleeding during one year after surgery was 87 % in the DAT treatment group and 67 % in the TAT treatment group (p=0.005). The incidence of secondary endpoints, including ischemic stroke, myocardial infarction, prosthetic valve thrombosis, and death, was statistically non-significant. Administration of DAT vs. TAT after heart valve replacement and myocardial revascularization significantly decreases the incidence of any bleedings in the absence of significant differences in the incidence of thromboembolic events and mortality.

Inverse Association of Lipoprotein(a) on Long-Term Bleeding Risk in Patients with Coronary Heart Disease: Insight from a Multicenter Cohort in Asia.

Lipoprotein(a), or Lp(a), has been recognized as a strong risk factor for atherosclerotic cardiovascular disease. However, the relationship between Lp(a) and bleeding remains indistinct, especially in the secondary prevention population of coronary artery disease (CAD). This investigation aimed to evaluate the association of Lp(a) with long-term bleeding among patients with CAD. Based on a prospective multicenter cohort of patients with CAD consecutively enrolled from January 2015 to May 2019 in China, the current analysis included 16,150 participants. Thus, according to Lp(a) quintiles, all subjects were divided into five groups. The primary endpoint was bleeding at 2-year follow-up, and the secondary endpoint was major bleeding at 2-year follow-up. A total of 2,747 (17.0%) bleeding and 525 (3.3%) major bleeding were recorded during a median follow-up of 2.0 years. Kaplan-Meier survival analysis showed the highest bleeding incidence in Lp(a) quintile 1, compared with patients in Lp(a) quintiles 2 to 5 (p < 0.001), while the incidence of major bleeding seemed similar between the two groups. Moreover, restricted cubic spline analysis suggested that there was an L-shaped association between Lp(a) and 2-year bleeding after adjustment for potential confounding factors, whereas there was no significant association between Lp(a) and 2-year major bleeding. There was an inverse and L-shaped association of Lp(a) with bleeding at 2-year follow-up in patients with CAD. More attention and effort should be made to increase the clinician awareness of Lp(a)'s role, as a novel marker for bleeding risk to better guide shared-decision making in clinical practice.

The clinical outcomes of different doses of rivaroxaban in patients with isolated distal deep vein thrombosis

ObjectiveIsolated distal deep vein thrombosis (IDDVT) is defined as thrombosis involving the infrapopliteal veins. The optimal anticoagulant therapy of IDDVT remains controversial. This study aimed to assess whether reduced dose of rivaroxaban was suitable in patients with IDDVT. MethodsConsecutive patients with acute IDDVT were identified by reviewing the venous thromboembolism (VTE) registry databases. Outcomes including VTE recurrence, major bleeding, clinically relevant non-major (CRNM) bleeding, and death. Patients were followed until the first occurrence of any outcomes or the study end date (December 31, 2018). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed. ResultsA total of 1246 patients were divided into low-dose (10 or 15 mg/day; n = 716) and standard-dose (20 mg/day; n = 530) groups. The incidences of VTE recurrence, major bleeding, CRNM bleeding, and death between the two groups were 9.64% vs 5.66%, 1.68% vs 3.02%, 4.61% vs 8.68%, and 13.83% vs 10.75%, respectively. After the inverse probability of treatment weighting, HRs for standard-dose vs low-dose of VTE recurrence, major bleeding, CRNM bleeding, and death were 0.54 (95% CI, 0.35-0.84), 1.71 (95% CI, 0.80-3.67), 2.28 (95% CI, 1.40-3.74), and 1.30 (95% CI, 0.91-1.86), respectively. For the subgroup analysis, the interaction with anticoagulation duration and treatment was evident for VTE recurrence (P for interaction = .002), but not for major bleeding. Patients with residual vein thrombosis were associated with an increased risk of VTE recurrence (HR, 1.95; 95% CI, 1.29-2.95). The interaction between risk factors and residual vein thrombosis was evident for VTE recurrence (P for interaction = .085). ConclusionsStandard-dose rivaroxaban reduced the risk of VTE recurrence without increasing the risk of major bleeding in patients with IDDVT. Anticoagulant therapy for >1.5 months should be preferred over shorter durations. Residual vein thrombosis should be assessed as a predictor of recurrence in patients with IDDVT, especially for patients with non-transient factors.

Validation of the academic research consortium high bleeding risk definition in Thai PCI registry

BackgroundBleeding following percutaneous coronary intervention (PCI) has important prognostic implications. The Academic Research Consortium (ARC) have identified a set of clinical criteria to standardize the definition of a high bleeding risk (HBR). Current study sought to externally validate the ARC definition for HBR patients in a contemporary real-world cohort. MethodThis post hoc analysis included 22,741 patients undergoing PCI between May 2018 and August 2019 enrolled in Thai PCI Registry. The primary endpoint was the incidence of major bleeding at 12 months post index PCI. ResultsIn total, 8678 (38.2%) and 14,063 (61.8%) patients were stratified to the ARC-HBR and non-ARC-HBR groups, respectively. Incidence of major bleeding was 3.3 and 1.1 per 1000 patients per month in the ARC-HBR group and the non-ARC-HBR group (HR 2.84 [95% CI: 2.39–3.38]; p < 0.001). Advanced age and heart failure met the 1-year major criteria performance goal of ≥4% major bleeding. The impact of HBR risk factors was incremental. HBR patients also experienced significantly higher rates of all-cause mortality (19.1% versus 5.2%, HR 4.00 [95% CI: 3.67–4.37]; p < 0.001) and myocardial infarction. The ARC-HBR score fairly performed in discriminating bleeding with C-statistic (95% CI) of 0.674 (0.649, 0.698). Updating the ARC-HBR by adding heart failure, prior myocardial infarction, non-radial access, female in the model significantly improved C-statistic of 0.714 (0.691, 0.737). ConclusionsThe ARC-HBR definition could identify patients at increased risk not only for bleeding but also for thrombotic events, including all-cause mortality. Coexistence of multiple ARC-HBR criteria unveiled additive prognostic value.

Incidence of bleeding and recurrence in isolated distal deep vein thrombosis: findings from the Venous Thrombosis Registry in Østfold Hospital

BackgroundIsolated distal deep vein thrombosis (IDDVT) is a common presentation of deep vein thrombosis. There are limited data on the long-term risk of recurrence after IDDVT. ObjectivesWe aimed to determine the short- and long-term incidence of venous thrombosis (VTE) recurrence after cessation of anticoagulation and the 3-month incidence of bleeding during anticoagulant treatment in patients with IDDVT. MethodsBetween January 2005 and May 2020, 475 patients with IDDVT and without active cancer were identified from the Venous Thrombosis Registry in Østfold Hospital, which is an ongoing registry of consecutive patients with VTE at Østfold Hospital, Norway. Major and clinically relevant, nonmajor bleeding as well as recurrent VTE were registered, and the cumulative incidences of these events were assessed. ResultsThe median age of the patients was 59 years (IQR, 48-72 years), 243 (51%) patients were women, and 175 events (36.8%) were classified as unprovoked. The 1-, 5-, and 10-year cumulative incidences of recurrent VTE were 5.6% (95% CI, 3.7-8.4), 14.7% (95% CI, 11.1-19.4), and 27.2% (95% CI, 21.1-34.5), respectively. The recurrence rates were higher for unprovoked IDDVT than for provoked IDDVT. Among the recurrent events, 18 (29%) were pulmonary embolisms and 21 (33%) were proximal deep vein thromboses. The 3-month cumulative incidence of major bleeding was 1.5% (95% CI, 0.7-3.1) overall and 0.8% (95% CI, 0.2-3.1) when restricted to patients treated with direct oral anticoagulants. ConclusionDespite initial treatment, the long-term risk of VTE recurrence after first-time IDDVT is high. The bleeding rates during anticoagulation, particularly with direct oral anticoagulants, were acceptably low.

Enoxaparin versus Placebo to Prevent Symptomatic Venous Thromboembolism in Hospitalized Older Adult Medical Patients

BackgroundAdmission to the hospital is a major risk factor for the development of venous thromboembolism (VTE). Whether thromboprophylaxis with low-molecular-weight heparin prevents symptomatic VTE in medically ill, hospitalized older adults remains debated.MethodsIn a prospective, randomized, placebo-controlled, double-blind, multicenter trial, older adults (>70 years of age) hospitalized for acute medical conditions were randomly assigned to receive 40 mg a day of low-molecular-weight heparin (enoxaparin) or placebo for 6 to 14 days. The primary efficacy outcome was the cumulative incidence of symptomatic VTE (distal or proximal deep vein thrombosis, fatal or nonfatal pulmonary embolism) at 30 days. The primary safety outcome was major bleeding. Secondary outcomes included efficacy and safety outcomes at 90 days.ResultsThe trial was prematurely discontinued in September 2020, 5 years after enrollment began, because of drug supply issues. By the time of trial discontinuation, 2559 patients had been randomly assigned at 47 centers. Median age was 82 years and 60% of patients were female. In the intention-to-treat population, the primary efficacy outcome occurred in 22 out of 1278 (cumulative incidence, 1.8%) patients in the enoxaparin group and in 27 out of 1263 (cumulative incidence, 2.2%) patients in the placebo group (cumulative incidence difference, −0.4 percentage points; 95% confidence interval, −1.5 to 0.7), with no significant difference in time to VTE (P=0.46). The incidence of major bleeding was 0.9% in the enoxaparin group and 1.0% in the placebo group. At 90 days there were 14 symptomatic pulmonary emboli in the enoxaparin group and 25 in the placebo group; all 39 pulmonary embolism events resulted in hospital readmission and/or death, with 5 deaths from pulmonary embolism in the enoxaparin group and 11 deaths in the placebo group.ConclusionsThis trial of thromboprophylaxis in medically ill, hospitalized older adults did not demonstrate that enoxaparin reduced the risk of symptomatic VTE after 1 month. Because the trial was prematurely discontinued, larger trials are needed to definitively address this question. (Funded by the French Ministry of Health Programme Hospitalier de Recherche Clinique, grant number PHRC-N-13-0283; ClinicalTrials.gov number, NCT02379806.)

Incidence of major bleeding in patients with chronic lymphocytic leukemia receiving ibrutinib and therapeutic anticoagulation

Increased rates of clinically significant bleeding have been reported with ibrutinib, however, limited data is available on the risk when given with concomitant therapeutic anticoagulation. We analyzed the incidence of major bleeding in 64 patient exposures that received ibrutinib with concomitant therapeutic anticoagulation. Major bleeding was observed in 5/64 (8%) patient exposures. The highest incidence was observed with rivaroxaban (3/17, 18%), followed by apixaban (2/35, 6%). No major bleeding events were seen with enoxaparin (n = 10). A total of 38% of patient exposures received a concomitant antiplatelet agent along with therapeutic anticoagulation. Among these patients, one (4%) experienced a fatal hemorrhage while taking ibrutinib, apixaban, and clopidogrel concomitantly. Our retrospective study observed a higher rate of major hemorrhage with combined DOAC with ibrutinib than historically reported with ibrutinib alone. This combination may be associated with increased risk of major bleeding and further prospective studies evaluating this risk are necessary.

Incidence of recurrent venous thromboembolism and bleeding complications in patients with cancer and isolated distal deep vein thrombosis

BackgroundIsolated distal deep vein thrombosis (IDDVT) is a common clinical presentation of DVT. The efficacy and safety of anticoagulant therapy for the management of IDDVT in patients with cancer are unclear. We sought to assess the incidence of recurrent venous thromboembolism (VTE) and major bleeding in this patient population. MethodsA systematic search of MEDLINE, EMBASE and PubMed, from inception to June 2, 2022 was performed. The primary efficacy outcome was recurrent VTE and the primary safety outcome was major bleeding. The secondary outcomes were clinically relevant non-major bleeding (CRNMB) and mortality. The incidence rates of thrombotic, bleeding, and mortality outcomes were pooled using random effects model and expressed as events per 100 patient-months with associated 95 % confidence intervals (CI). ResultsOut of a total of 5234 articles, 10 observational studies including 8160 patients with cancer and IDDVT were included in the analysis. The incidence rate of recurrent VTE was 5.65 (95 % CI: 2.09–15.30) per 100 patient-years regardless of type and duration of anticoagulant therapy. The incidence rate of major bleeding was 4.08 (95 % CI: 2.52–6.61) per 100 patient-years. The incidence rates for CRNMB and mortality per 100 patient-years were 8.11 (95 % CI: 5.56–11.83) and 30.22 (95 % CI: 22.60–40.42.89), respectively. ConclusionPatients with cancer and IDDVT are at high risk of developing recurrent VTE and bleeding complications (both major bleeding and CRNMB). More studies are needed to define the optimal management for this high-risk population.

Outcomes and Institutional Variation in Arterial Access Among Patients With AMI and Cardiogenic Shock Undergoing PCI

BackgroundContemporary data comparing the outcomes of transradial access (TRA) vs transfemoral access (TFA) among patients presenting with acute myocardial infarction and cardiogenic shock (AMI-CS) undergoing percutaneous coronary intervention (PCI) are limited. ObjectivesThis study examines in-hospital outcomes and institutional variation among patients with AMI-CS undergoing TRA-PCI vs TFA-PCI. MethodsPatients admitted with AMI-CS from the NCDR CathPCI registry between April 2018 and June 2021 were included. Multivariable logistic regression and inverse probability weighting models were used to assess the association between access site and in-hospital outcomes. A falsification analysis using non-access site–related bleeding was performed. ResultsAmong 35,944 patients with AMI-CS undergoing PCI, 25.6% were performed with TRA. The proportion of TRA-PCI increased over the study period (22.0% in the second quarter of 2018 vs 29.1% in the second quarter of 2021; P-trend <0.001). Significant institutional-level variability in the use of TRA-PCI was also observed: 20.9% of all sites using TRA in <2% of PCIs (low utilization) vs 1.9% of all sites using TRA in >80% of PCIs (high utilization). Patients undergoing TRA-PCI had a significantly lower adjusted incidence of major bleeding (odds ratio [OR]: 0.71; 95% confidence interval [CI]: 0.67-0.76), mortality (OR: 0.73; 95% CI: 0.69-0.78), vascular complications (OR: 0.67; 95% CI: 0.54-0.84), and new dialysis (OR: 0.86; 95% CI: 0.77-0.97). There was no difference in non-access site related bleeding (OR: 0.93; 95% CI: 0.84-1.03). Sensitivity analyses revealed similar benefit with TRA-PCI among patients without arterial cross-over. There were no significant interactions observed between TRA-PCI with mechanical circulatory support and in-hospital outcomes. ConclusionsIn this large nationwide contemporary analysis of patients with AMI-CS, about quarter of PCIs were performed via TRA with wide variability across US institutions. TRA-PCI was associated with significantly lower incidence of in-hospital major bleeding, mortality, vascular complications, and new dialysis. This benefit was observed irrespective of mechanical circulatory support use.

Comparison of clinical outcomes with cangrelor plus aspirin versus oral dual antiplatelet therapy in patients supported with venoarterial extracorporeal membrane oxygenation.

Patients with refractory cardiogenic shock from an acute myocardial infarction may receive percutaneous coronary intervention (PCI) and require the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO). The purpose of this study was to compare bleeding and thrombotic events in patients treated with cangrelor plus aspirin versus oral dual antiplatelet therapy (DAPT) while supported with VA-ECMO. We conducted a retrospective review of patients who received PCI, were supported with VA-ECMO, and were treated with either cangrelor plus aspirin or oral DAPT from February 2016 through May 2021 at Allegheny General Hospital. The primary objective was the incidence of major bleeding, defined as Bleeding Academic Research Consortium (BARC) type 3 or greater. The incidence of thrombotic events was a secondary objective. Thirty-seven patients were included, 19 in the cangrelor plus aspirin group, and 18 in the oral DAPT group. All the patients in the cangrelor group received a dose of 0.75 mcg/kg/min. Major bleeding occurred in 7 patients (36.8%) in the cangrelor group compared to 7 patients (38.9%) in the oral DAPT group (p = 0.90). No patient developed stent thrombosis. Two patients (10.5%) in the cangrelor group had a thrombotic event versus 3 patients (16.7%) in the oral DAPT group (p = 0.66). Bleeding and thrombotic events were comparable between patients receiving cangrelor plus aspirin versus oral DAPT while on VA-ECMO.

ARTERIAL HYPERTENSION AS A PREDICTOR OF THROMBOEMBOLIC EVENTS IN PATIENTS WITH ATRIAL FIBRILLATION TREATED WITH DIRECT ORAL ANTICOAGULANTS

Objective: The aim of the study was to assess predictors of thromboembolic events in patients with atrial fibrillation treated with direct oral anticoagulants (DOAC). Design and method: From our single-centre prospective registry we enrolled 2792 consecutive atrial fibrillation patients that were started on dabigatran, rivaroxaban or apixaban. The mean duration of treatment exposure was 724 days. The primary outcome was the incidence of thromboembolic events. The incidence of bleeding events and death were also assessed. Potential risk factors for thromboembolic events were evaluated using Cox regression analysis. Results: During the follow-up, 94 patients experienced a thromboembolic event (1.9%/year). Twelve patients experienced two and one patient experienced three thromboembolic events. Considering only the first thromboembolic event, 39 patients experienced a stroke, 14 patients a transient ischaemic attack (TIA), 12 patients a systemic thromboembolism (SE), 19 patients myocardial infarction (MI) and 10 patients a venous thromboembolic event. Twelve thromboembolic events were fatal (0.2%/year). According to a multivariate Cox regression analysis (Table 1), significant predictors for a composite endpoint of stroke, TIA, SE and MI were age group (HR 1.27, 95% CI 1.04–1.56, p = 0.022), arterial hypertension (HR 2.86, 95% CI 1.15–7.12, p = 0.024) and history of stroke, TIA or SE (HR 2.6, 95% CI 1.66–4.05, p &lt; 0.001). The incidence of major bleeding was 2.3%/year. Conclusions: In this prospective clinical study we have shown that age, arterial hypertension and history of stroke, TIA or SE were strong predictors of arterial thromboembolic events in patients with atrial fibrillation treated with DOAC. Among those, arterial hypertension had the highest hazard ratio. Since arterial hypertension presents a potentially modifiable predictor, it can be assumed that its treatment was not adequate.

PEDS4: Postoperative anticoagulation with bivalirudin versus heparin for HeartMate 3 in children

Background: Bivalirudin has become the standard of care for paracorporeal VAD support in children, although its utilization and outcomes in children with intracorporeal VADs have not been thoroughly studied. We compared the outcomes in children receiving bivalirudin versus unfractionated heparin (UFH) for early (<14 days) post-operative thromboprophylaxis. Methods: Using the ACTION network registry, we conducted a multicenter, retrospective analysis with all patients receiving bivalirudin or UFH for HeartMate 3 (HM3). Survival and adverse events in 14 days post VAD implantation were compared between patients receiving bivalirudin, UFH, or both agents. Results: Between 4/1/18-7/31/22, 171 patients with median age 15.3 years (IQR 12.9-17.3) and weight 62 kg (IQR 45-81) underwent HM3 implantation. Of these, 65 (38%) received bivalirudin, 91 (53%) received UFH and 15 (8.7%) received both agents. At 2 weeks, there was 100% survival in the bivalirudin group, 98% survival in the UFH group, and 100% survival in the bivalirudin/UFH group (p=0.65). Stroke incidence was similar across all anticoagulation agents [4 (6.1%) bivalirudin, 5 (5.5%) UFH, 1 (6.7%) bivalirudin/UFH, p=0.99]. Major bleeding incidence was similar across the anticoagulation agents [2 (3%) bivalirudin, 5 (5.5%) UFH, 1 (6.7%) bivalirudin/UFH, p=0.6). Hemolysis was lower in patients treated with bivalirudin [3 (4.6%)] versus UFH [7 (7.6%)] and bivalirudin/UFH [3 (33%)], p=0.006. Conclusions: In pediatric patients with a HeartMate3, anticoagulation with bivalirudin resulted in similar survival, stroke-free survival, and bleeding-free survival compared to UFH, with lower hemolysis with bivalirudin. More evaluation is required to understand the burden of post-operative hemocompatibility related adverse events.

Safety of the Pulmonary Embolism Rule-Out Criteria Rule: Findings from the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) Registry.

The diagnostic strategy for pulmonary embolism (PE) includes a D-dimer test when PE probability is low or intermediate, but false positive D-dimer results are frequent and can result in an unnecessary computed tomography pulmonary angiogram. The PE rule-out criteria (PERC) rule excludes PE without D-dimer testing when pre-test probability is <15%. The aim of this study was to assess the safety of the PERC rule strategy in patients included in the Registro Informatizado de la Enfermedad TromboEmbolica venosa (RIETE) registry. This retrospective cohort study used data from the RIETE registry, an ongoing, international prospective registry of patients with objectively confirmed venous thromboembolism. The primary outcome was the failure rate of the PERC strategy, represented by the proportion of PERC-negative (PERC-N) patients with a PE included in the registry. Secondary outcomes were a comparison of the clinical characteristics, treatment strategy, and outcome of PERC-N versus PERC-positive (PERC-P) patients at 3 months. From 2001 to 2021, 49,793 patients with acute PE were enrolled in the RIETE registry. We included 48,903 in the final analysis after exclusion of 890 patients with an undetermined PERC status. Only 346 patients were PERC-N with a failure rate of 0.7% (95% confidence interval 0.6-0.8%). PERC-N patients presented more frequently with chest pain, but less often with dyspnea, syncope or hypotension. They had also sub-segmental or segmental PE more frequently, were more often treated with direct oral anticoagulants, and received mechanical or pharmacological thrombolysis less often. In addition, PERC-N patients had a lower incidence of recurrent deep vein thrombosis, major bleeding, and death attributed to PE during the 3-month follow-up. A low failure rate of the PERC rule was observed in the RIETE registry, thus supporting its use to safely identify patients with an unlikely probability of PE.

Prognostic value of chronic kidney disease in patients undergoing left atrial appendage occlusion

Abstract Funding Acknowledgements Type of funding sources: None. Background Atrial fibrillation (AF) and chronic kidney disease (CKD) often coexist and share an increased risk of thromboembolic events. CKD concomitantly contributes to several pathophysiological changes predisposing towards a pro-haemorrhagic state. Purpose To evaluate the impact of kidney function on peri-procedural complications and clinical outcomes in AF patients undergoing left atrial appendage occlusion (LAAO) with a Watchman device. Methods 2124 consecutive AF patients undergoing Watchman implantation at 8 different centers were categorized into CKD stage 1+2 (n=1089), CKD stage 3 (n=796), CKD stage 4 (n=170), CKD stage 5 (n=69) based on the estimated glomerular filtration rate at baseline. The primary efficacy endpoint included a composite of cardiovascular (CV) mortality, stroke, transient ischemic attack, peripheral thromboembolism (TE), and major bleeding. Results A non-significant higher incidence of major peri-procedural adverse events (1.7% vs. 2.3% vs. 4.1% vs. 4.3%) was observed with worsening baseline kidney function (p=0.14). The mean follow-up period was 13 ± 7 months [2226 patient-years (PY)]. In comparison to CKD stage 1+2 as a reference, the incidence of the primary endpoint was significantly higher in CKD stage 3 (log-rank p-value= 0.04), CKD stage 4 (log-rank p-value= 0.01), and CKD stage 5 (log-rank p-value= 0.001) (Fig.1A). A non-significant increase in event rates for stroke/TIA and clinically relevant bleeding was observed among the four groups. LAAO led to a TE risk reduction of 72%, 66%, 62%, and 41% in each group (Fig.1B). The relative risk reduction in the incidence of major bleeding was 58%, 44%, 51%, and 52%, respectively (Fig.1C). Conclusion Patients with moderate-to-severe CKD had a higher incidence of the primary composite endpoint. However, the relative risk reduction in the incidence of TE and major bleeding was consistent across CKD groups, irrespective of the very different risk profiles at baseline.

Choice of anticoagulation in patients with low risk antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is an acquired hypercoagulable state necessitating long-term anticoagulation for secondary thrombosis prevention. Anticoagulation guidelines are predominantly based on data in high risk, triple positive patients, and favor Vitamin K antagonists over other forms of anticoagulation. The efficacy of alternative anticoagulants for secondary thrombosis prevention in low risk, single and double positive APS remains uncertain.This study aimed to assess the incidence of recurrent thrombosis and major bleeding for patient with low risk APS on long-term anticoagulation.We performed a retrospective cohort study of patients who met revised criteria for thrombotic APS between January, 2001 and April, 2021 and received care through the Lifespan Health System. Primary outcomes included recurrent thrombosis and WHO Grades 3 and 4 major bleeding.A total of 190 patients were followed over a median duration of 3.1 years. At time of APS diagnosis, 89 patients were treated with warfarin and 59 patients with a direct oral anticoagulant (DOAC). There were similar rates of recurrent thrombosis in low risk patients on warfarin versus DOACs (adjusted IRR 6.91; 95% CI 0.90-53.40, p = 0.064). Major bleeding events only occurred in low risk patients on warfarin (n = 8, log-rank p = 0.13). In conclusion, despite the choice of anticoagulation, patients with low risk APS hadsimilar rates of recurrent thrombosis suggesting DOACs may bea potential treatment option for this cohort. There was a non-significant increase in major bleeding rates in low risk patients on warfarin versus DOACs. Study limitations include a retrospective study design and small event numbers.

Aspirin as a thromboprophylaxis agent after revision knee arthroplasty: A retrospective analysis

IntroductionTotal knee arthroplasty is a common and effective procedure. Although complication rates are low, certain complications such as venous thromboembolism are potentially serious. The optimal prophylactic agent and dosage after revision knee arthroplasty remains unclear. The main objective of this work was to study the efficacy and safety of aspirin as a thromboprophylaxis agent following revision knee arthroplasties. Patients and methodsA retrospective review of patients undergoing revision knee arthroplasty between 2013 and 2020at a University Teaching Hospital was undertaken. The primary outcome was the development of a symptomatic thromboembolic event requiring treatment within 90 days post-surgery. The secondary outcomes were adverse events associated with aspirin therapy: surgical site infection rate; incidence of major bleeding; readmission rate and mortality within 90 days post-surgery. Results490 patients were included. 374 (76.3%) received prophylactic aspirin (150 mg once daily for 28 days) and 75 (15.3%) patients received dalteparin for 28 days due to contraindication to aspirin use. Those already receiving other thromboprophylaxis agents for pre-existing comorbidities continued these after relevant medical consultation. The overall rates of venous thromboembolism and symptomatic DVT after aspirin prophylaxis were 0.6% (3/490) and 0.8% (3/374), respectively. VTE incidence did not significantly differ between those administered aspirin and other agents. No patient experienced major bleeding within 90 postoperative days. Only 2 of 490 (0.4%) patients had wound infection requiring readmission; neither received prophylactic aspirin. ConclusionExtended out-of-hospital thromboembolic prophylaxis with aspirin may be at least as effective as other agents in patients undergoing revision knee arthroplasty. Aspirin is safe, effective, and cheap compared with other agents.

ORal anticoaGulants in diAbetic and Nondiabetic patients with nOn-valvular atrial fibrillatioN (ORGANON)

BackgroundDiabetes represents a pro-thrombotic condition. ObjectivesThe primary objective was to evaluate the effects of Vitamin K Antagonist (VKA) compared to direct oral anticoagulants (DOACs) in diabetic and nondiabetic patients with non-valvular atrial fibrillation, newly diagnosed. The secondary objective was to evaluate the effects on the risk of bleeding. MethodsWe enrolled 300 patients with newly diagnosed atrial fibrillation. One hundred and sixteen patients were taking warfarin, 31 acenocumarol, 22 dabigatran, 80 rivaroxaban, 34 apixaban, and 17 edoxaban. We evaluated: anthropometric parameters, glycated hemoglobin (HbA1c), fasting and post-prandial glucose (FPG, and PPG), lipid profile, Lp(a), small and dense low-density lipoprotein (SD-LDL), oxidized LDL (Ox-LDL), I-troponin (I-Tn), creatinine, transaminases, iron, red blood cells (RBC); hemoglobin (Hb), platelets (PLT), fibrinogen, D-dimer, anti-thrombin III, C-reactive protein (Hs-CRP), Metalloproteinases-2 (MMP-2), Metalloproteinases-9 (MMP-9), and incidence of bleeding. ResultsWe did not record any differences among nondiabetic patients between VKA and DOACs. However, when we considered diabetic patients, we found a slight, but significant improvement of triglycerides and SD-LDL. As regards incidence of bleeding, minor bleeding was more frequent in VKA diabetic group compared to DOACs diabetic group; furthermore, the incidence of major bleeding was higher with VKA in nondiabetic and diabetic group, compared to patients with DOACs. Among DOACs, we recorded a higher incidence of bleeding (minor and major) with dabigatran compared to rivaroxaban, apixaban and edoxaban in nondiabetic and diabetic patients. ConclusionDOACs seem to be metabolically favourable in diabetic patients. Regarding incidence of bleeding, DOACs with the exception of dabigatran, seem better than VKA in diabetic patients.

Predicting post-discharge venous thromboembolism and bleeding among medical patients: External validation of a novel risk score utilizing ubiquitous biomarkers

BackgroundPost-hospitalization thromboprophylaxis can reduce venous thromboembolism (VTE) risk for non-surgical patients but may carry bleeding risks. We aimed to externally validate the Intermountain Risk Scores for hospital-associated venous thromboembolism (HA-VTE IMRS) and major bleeding (HA-MB IMRS) for VTE and bleeding outcomes. MethodsRetrospective cohort study of adult patients discharged alive from medical services between 2015 and 2019. HA-VTE IMRS and HA-MB IMRS were calculated at the time of hospital discharge and dichotomized as high- or low-risk as described in the derivation manuscript. 90-day post-discharge VTE outcomes were assessed from diagnostic radiology reports, and bleeding outcomes were assessed using ICD-10 codes and blood bank transfusion records. ResultsAmong 113,578 patients in the study, 66,340 patients (58.4 %) had a low-risk HA-VTE IMRS <7, versus 47,238 (41.6 %) high-risk ≥7. For bleed prediction, 71,576 patients (63 %) had a low-risk HA-MB IMRS <8, versus 42,002 (37 %) high-risk ≥8. VTE incidence was 1.1 % and 0.6 % while major bleeding incidence was 1.3 % and 0.1 % in high-risk versus low-risk cohorts, respectively. AUCs for VTE and bleed outcome discrimination were 0.59 and 0.78, respectively. Patients with a combined high-risk VTE score and low-risk bleeding score comprised 14.5 % of the population. ConclusionIn this external validation study, the HA-VTE IMRS had poor discrimination for VTE but the HA-MB IMRS had good discriminatory ability for major bleeding events. A sizable minority of patients were categorized as high VTE risk with low bleed risk, a population which may have an optimal risk-benefit profile for post-hospital thromboprophylaxis.