Rate Of Bleeding Events Research Articles

Treatment of Bleeding Episodes with Efanesoctocog Alfa in Children with Severe Hemophilia A in the XTEND-Kids Phase 3 Study

Introduction Efanesoctocog alfa (formerly BIVV001) is a new class of high sustained factor VIII (FVIII) replacement therapy, composed of a single recombinant FVIII protein fused to dimeric Fc protein, 2 XTEN polypeptides, and the D'D3 domain of von Willebrand factor (VWF), designed to overcome the endogenous VWF-imposed half-life ceiling. The XTEND-Kids (NCT04759131) study demonstrated once-weekly efanesoctocog alfa was well tolerated and provided effective treatment of and protection from bleeds in previously treated patients <12 years old with severe hemophilia A. Here, we provide a detailed report on efanesoctocog alfa as a treatment for bleeds during XTEND-Kids. Methods Previously treated patients <12 years old (≥150 exposure days [EDs] for patients 6 to <12 years of age and ≥50 EDs for patients <6 years old) with severe hemophilia A (<1 IU/dL [<1%] endogenous FVIII activity or a documented genotype associated with severe hemophilia) received efanesoctocog alfa 50 IU/kg once weekly for 52 weeks. In line with the study protocol, bleeds were treated with a single dose of efanesoctocog alfa (50 IU/kg). Additional doses (30 or 50 IU/kg, every 2-3 days) could be considered if needed. For minor/moderate bleeds occurring within 2-3 days of a recent prophylactic dose, a 30 IU/kg dose could also be used. The number and location of bleeds, as well as dose and number of efanesoctocog alfa injections required to resolve them were recorded. Patient assessment of the response to the first injection for treating a bleed was evaluated using the 4-point International Society on Thrombosis and Haemostasis (ISTH) scale (excellent, good, moderate, and none). Results Of 74 patients in XTEND-Kids, 73 were included in these post hoc analyses, including 38 subjects <6 years of age. One subject in the 6 to <12 group was excluded from these analyses as he did not receive weekly prophylaxis treatment as specified in the protocol, instead receiving intense consolidation treatment (2-3 injections per week for ~4 months) following 2 traumatic self-reported hip bleeds (however, no signs of bleeding or joint damage were observed by magnetic resonance imaging during the consolidation treatment period). The mean (SD) total number of EDs was 52.3 (6.83) for the overall population. The mean (95% confidence interval [CI]) estimated annualized bleed rate (ABR) was 0.61 (0.42-0.90). The mean (95% CI) annualized spontaneous, traumatic, and joint bleed rates were 0.16 (0.08-0.31), 0.40 (0.24-0.65), and 0.30 (0.16-0.57), respectively. Eighty-six percent of participants (n=63) had ≤1 bleed, including 64% (n=47) with no overall bleeds; 88% (n=64) had no spontaneous bleeds and 84% (n=61) had no joint bleeds. There were 43 bleeds treated with efanesoctocog alfa, of which 11 were reported as spontaneous (26%), 28 as traumatic (65%), and 4 (9%) were of unknown etiology (Table). The most common locations for bleeds were the joints (n=21, 49%) and skin/mucosa (n=15, 35%). The rate of bleeding events per week throughout the study remained consistently low (Figure). The mean (SD) duration between a treated bleed and nearest injection taken prior to that bleed was 4.7 (1.95) days, with a mean of 4.5 (1.56) days for a spontaneous bleed and 4.8 (2.12) for traumatic bleeds. A single injection was sufficient to resolve 95% of bleeds, and no bleed required more than 2 injections for resolution. The median (interquartile range) total dose required to resolve a bleed was 52.6 (50.0-55.8) IU/kg. Among first injections for bleeding episodes with an evaluation of response by participants (n=37), the vast majority (n=36, 97%) were rated as excellent or good. Conclusions A single dose of efanesoctocog alfa 50 IU/kg resolved 95% of bleeds in children <12 years of age, regardless of type or location. The hemostatic efficacy of efanesoctocog alfa was rated as excellent or good for nearly all evaluated first injections (97%). Once-weekly efanesoctocog alfa provided efficient prophylaxis with no bleeds in 64% of participants, and consistently low ABRs among all types and locations of bleeds. Efanesoctocog alfa provided effective treatment and prevention of bleeds in previously treated children <12 years of age with severe hemophilia A.

Real-World Effectiveness and Safety Outcomes of Acalabrutinib Treatment By Line of Therapy in Patients with Chronic Lymphocytic Leukemia and/or Small Lymphocytic Lymphoma

Background: Acalabrutinib is a second-generation Bruton tyrosine kinase inhibitor (BTKi) approved by the Food and Drug Administration for the treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Data from phase 3, randomized, controlled trials of acalabrutinib, as monotherapy or in combination with obinutuzumab, in patients with treatment-naive (TN) and relapsed/refractory (R/R) CLL with long-term follow-up, including ELEVATE-TN, ELEVATE-RR, and ASCEND, have demonstrated sustained improvement vs comparators in progression-free survival and overall survival (OS) with cardiovascular (CV) and bleeding events consistent with previous reports (Sharman et al. J Clin Oncol. 2021; Byrd et al. J Clin Oncol. 2021; Ghia et al. Blood. 2022). As real-world evidence of the acalabrutinib effectiveness and safety profile is limited in CLL/SLL patients, this study aimed to describe time to next treatment (TTNT), OS, and CV and bleeding events in patients receiving first-line (1L) and later-line (2L+) acalabrutinib for the treatment of CLL/SLL in the real-world setting. Methods: A retrospective, observational analysis was conducted utilizing the Optum Clinformatics © Data Mart claims and electronic medical record database to identify patients aged ≥18 years with TN or R/R CLL/SLL who initiated acalabrutinib in any line of therapy (LoT) on or after November 21, 2019 (FDA approval date for acalabrutinib). Patients with CLL/SLL were required to have ≥6 months of continuous enrollment in the Optum database system prior to acalabrutinib treatment initiation. Patients were followed until the earliest of last day of data availability, death, or end of study period (September 30, 2022). Treatment effectiveness was described as TTNT (time from acalabrutinib initiation to next LoT or death of any cause) and OS (time from acalabrutinib initiation to date of death from any cause or end of study period). The Kaplan-Meier (KM) method was used to estimate TTNT and OS. Patients who continued treatment at the last follow-up were censored. CV and bleeding events were assessed in all patients who initiated acalabrutinib. All outcomes were evaluated in patients who received 1L or 2L+ acalabrutinib therapy. Results: A total of 530 patients were identified and included in the analysis. Of these patients, 63% (n=334) received 1L acalabrutinib and 37% (n=196) received 2L+ acalabrutinib. At acalabrutinib initiation, the mean age was 72.8 years in the 1L cohort and 74.2 years in the 2L+ cohort; 61.7% (121/196) of patients treated with 2L+ acalabrutinib had prior BTKi therapy prior to acalabrutinib initiation (ibrutinib, n=120; zanubrutinib, n=1). Distributions of gender and race were similar between the cohorts. At baseline, 18.1%, 75.3%, and 16.0% of patients had atrial fibrillation/flutter, hypertension, and bleeding episodes, respectively. With a median follow-up of 8.9 months in the 1L cohort and 12.4 months in the 2L+ cohort, the median TTNT and OS were not reached in either cohort. At 18 months, the proportion of patients remaining on treatment was 82% in the 1L cohort and 78% in the 2L+ cohort ( Figure 1). Of the patients that progressed, the median TTNT was 4.0 months in the 1L cohort (n=33) and 4.2 months in the 2L cohort (n=31). The 18-month OS rate was 90% and 85% for the 1L and 2L+ cohorts, respectively ( Figure 2). After initiation of acalabrutinib treatment, the incidence rates of atrial fibrillation/flutter, hypertension, and bleeding events were 2.7%, 8.9%, and 2.7% of patients in the 1L cohort and 7.4%, 2.4%, and 3.3% of patients in the 2L+ cohort, respectively, who had no history of these events prior to treatment with acalabrutinib. Conclusions: This is the first study demonstrating real-world effectiveness (OS and TTNT) and safety data of acalabrutinib treatment in first-line and later-line therapy. While clinical trial and clinical practice settings may differ, overall, the survival findings in this study were similar to those of acalabrutinib trials. The observed incidence rates of CV and bleeding events were not inconsistent with those observed in published acalabrutinib trials.

Management of patients after total knee arthroplasty using mechanical prophylaxis and reduced doses of edoxaban: A retrospective cohort study.

Edoxaban is given as pharmacologic prophylaxis alone or in combination with mechanical prophylaxis for venous thromboembolism after total knee arthroplasty. Several choices are made regarding edoxaban dosages when used in combination with mechanical prophylaxis. This study aimed to compare efficacy and safety in patients who received edoxaban with elastic stockings after total knee arthroplasty between those who received the standard dose, including those who received a reduced dose after meeting dose reduction criteria, and those who received reduced doses without dose reduction criteria. This study included 143 patients in the standard-dose group (with 125 patients receiving dose-adjusted edoxaban 15 mg/day) and 110 patients in the low-dose group, and it compared the incidence of venous thromboembolism and bleeding events between groups. The impact of edoxaban administration on the occurrence of venous thromboembolism after total knee arthroplasty was also examined using multivariate regression analysis. Our results showed that rates of venous thromboembolism and bleeding events in patients wearing elastic stockings after total knee arthroplasty were similar in both standard- and low-dose groups. Multivariate regression analysis showed that use of reduced-dose edoxaban without dose adjustment did not correlate with the occurrence of venous thromboembolism, but edoxaban administration was significantly associated with older age and longer surgery time (odds ratio 1.84, 95% confidence interval 1.04-3.25, p=0.036; odds ratio 1.69; 95% confidence interval 1.09-2.62, p=0.019). These results suggest that reduced dose selection of edoxaban for patients who receive mechanical prophylaxis after total knee arthroplasty and post-administration pharmacological management may be useful.

Giroctocogene fitelparvovec gene therapy for severe hemophilia A: 104-week analysis of the phase 1/2 Alta study

AbstractPatients with hemophilia A require exogenous factor VIII (FVIII) or nonfactor hemostatic agents to prevent spontaneous bleeding events. Adeno-associated virus (AAV) vector–based gene therapy is under clinical investigation to enable endogenous FVIII production. Giroctocogene fitelparvovec is a recombinant AAV serotype 6 vector containing the coding sequence for the B-domain–deleted human F8 gene. In the ongoing phase 1/2, dose-ranging Alta study, 4 sequential cohorts of male participants with severe hemophilia A received a single IV dose of giroctocogene fitelparvovec. The primary end points are safety and changes in circulating FVIII activity. Interim results up to 214 weeks after treatment for all participants are presented. Eleven participants were dosed. Increases in alanine and aspartate aminotransferases were the most common treatment-related adverse events (AEs), which resolved with corticosteroid administration. Two treatment-related serious AEs (hypotension and pyrexia) were reported in 1 participant within 6 hours of infusion and resolved within 24 hours after infusion. At the highest dose level (3 × 1013 vg/kg; n = 5), the mean circulating FVIII activity level at week 52 was 42.6% (range, 7.8%-122.3%), and at week 104 it was 25.4% (range, 0.9%-71.6%) based on a chromogenic assay. No liver masses, thrombotic events, or confirmed inhibitors were detected in any participant. These interim 104-week data suggest that giroctocogene fitelparvovec is generally well tolerated with appropriate clinical management and has the potential to provide clinically meaningful FVIII activity levels, as indicated by the low rate of bleeding events in the highest dose cohort. This trial was registered at www.clinicaltrials.gov as #NCT03061201.

Coagulation-monitored, dose-adjusted catheter-directed thrombolysis or pharmaco-mechanical thrombus removal in deep vein thrombosis.

Background: Pharmaco-mechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) are therapeutic options for selected patients with acute deep vein thrombosis (DVT) to prevent post-thrombotic syndrome (PTS). Patients and methods: We aimed to describe the clinical characteristics and outcomes of 159 patients with symptomatic iliofemoral DVT undergoing PMT alone, CDT alone, or CDT followed by PMT (bail-out) in the Swiss Venous Stent Registry. The primary outcome was the incidence of peri-interventional major and minor bleeding complications (ISTH criteria). Secondary outcomes included the incidence of PTS and stent patency after 3 years. Results: Mean age was 49±20 years and 58% were women. DVT involved the iliac veins in 99% of patients, whereas 53% had an underlying iliac vein compression. PMT alone was used in 40 patients, CDT alone in 77, and 42 received initial CDT followed by bail-out PMT due to insufficient thrombus clearance. Single-session PMT was the preferred approach in patients with iliac vein compression, patent popliteal vein, and absence of IVC thrombus. Patients treated with PMT alone received a lower r-tPA dose (median 10 mg, IQR 10-10) vs. those treated with CDT (20 mg, IQR 10-30). The rate of peri-interventional major bleeding was 0%, 1%, and 2%, whereas that of minor bleeding was 0%, 1%, and 12%, respectively, all occurring during CDT. After 3 years, PTS occurred in 6%, 9%, and 7% of patients, respectively. The primary stent patency rate was 95%, 88%, and 83%, respectively. Conclusions: The use of PMT and CDT for iliofemoral DVT was overall safe and resulted in high long-term patency and treatment success. Given the less severe presentation of DVT, single-session PMT appeared to be characterized by numerically better primary patency and lower perioperative bleeding event rates than CDT.

Safety and Efficacy of Uninterrupted Oral Anticoagulation in Patients Undergoing Catheter Ablation for Atrial Fibrillation with Different Techniques.

The safety and efficacy of an uninterrupted direct anticoagulation (DOAC) strategy during catheter ablation (CA) for atrial fibrillation (AF) has not been fully investigated with different ablation techniques. We evaluated consecutive AF patients undergoing catheter ablation with three different techniques. All patients were managed with an uninterrupted DOAC strategy. The primary endpoint was the rate of periprocedural thromboembolic and bleeding events. The secondary endpoints of the study were the rate of MACE and bleeding events at one-year follow-up. In total, 162 patients were enrolled. Overall, 53 were female and the median age was 60 [55.5-69.5] years. The median CHA2DS2-VASc and HAS-BLED scores were 2 [1-4] and 2 [1-2], respectively. In total, 16 patients had a past stroke or TIA while 11 had a predisposition or a history of bleeding. The CA procedure was performed with different techniques: RF 43%, cryoballoon 37%, or laser-balloon 20%. Overall, 35.8% were on rivaroxaban, 20.4% were on edoxaban, 6.8% were on apixaban, and 3.7% were on dabigatran. All other patients were all naïve to DOACs; the first anticoagulant dose was given before the ablation procedure. As for periprocedural complications, we found three groin hematomas not requiring interventions, one ischemic stroke, and one systemic air embolism (the last two likely due to several catheter changes through the transeptal sheath). Five patients reached the secondary endpoints: one patient for a myocardial infarction while four patients experienced minor bleeding during 1-year follow-up. Our results corroborate the safety and the efficacy of uninterrupted DOAC strategy in patients undergoing CA for AF, regardless of the ablation technique.

Model-Guided Decision-Making for Thromboprophylaxis and Hospital-Acquired Thromboembolic Events Among Hospitalized Children and Adolescents

Rates of hospital-acquired venous thromboembolism (HA-VTE) are increasing among pediatric patients. Identifying at-risk patients for whom prophylactic interventions should be considered remains challenging. To determine whether use of a previously validated HA-VTE prognostic model, together with pediatric hematologist review, could reduce pediatric inpatient rates of HA-VTE. This pragmatic randomized clinical trial was performed from November 2, 2020, through January 31, 2022, at a single-center academic children's hospital (Monroe Carell Jr Children's Hospital at Vanderbilt). All pediatric hospital admissions (aged <22 years) under inpatient status were included and randomized. All patients had an HA-VTE probability automatically calculated daily, which was visible to the hematology research team for patients in the intervention group. Patients with an elevated risk (predicted probability ≥2.5%) underwent additional medical record review by the research team to determine eligibility for thromboprophylaxis. The primary outcome was rate of HA-VTE. Secondary outcomes included rates of prophylactic anticoagulation and anticoagulation-associated bleeding events. A total of 17 427 hospitalizations met eligibility criteria, were randomized, and were included in the primary analysis: patients had a median (IQR) age of 1.7 (0 to 11.1) years; there were 9143 (52.5%) female patients and 8284 (47.5%) male patients, and there were 445 (2.6%) Asian patients, 2739 (15.9%) Black patients, and 11 752 (67.4%) White patients. The 2 groups were evenly balanced in number (8717 in the intervention group and 8710 in the control group) and patient characteristics. A total of 58 patients (0.7%) in the control group and 77 (0.9%) in the intervention group developed HA-VTE (risk difference: 2.2 per 1000 patients; 95% CI, -0.4 to 4.8 per 1000 patients; P = .10). Recommendations to initiate thromboprophylaxis were accepted by primary clinical teams 25.8% of the time (74 of 287 hospitalizations). Minor bleeding events were rare among patients who received anticoagulation (3 of 74 [4.1%]), and no major bleeding events were observed during the study period. Among patients randomized to the control group, the model exhibited high discrimination accuracy (C statistic, 0.799, 95% CI, 0.725 to 0.856). In this randomized clinical trial of the use of a HA-VTE prognostic model to reduce pediatric inpatient rates of HA-VTE, despite the use of an accurate and validated prognostic model for HA-VTE, there was substantial reluctance by primary clinical teams to initiate thromboprophylaxis as recommended. In this context, rates of HA-VTE between the control and intervention groups were not different. Future research is needed to identify improved strategies for prevention of HA-VTE and to overcome clinician concerns regarding thromboprophylaxis. ClinicalTrials.gov Identifier: NCT04574895.

The machine learning methods to analyze the using strategy of antiplatelet drugs in ischaemic stroke patients with gastrointestinal haemorrhage

BackgroundFor ischaemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs or reducing the dose of antiplatelet drugs was a conventional clinical therapy method. But not a study to prove which way was better. And the machinery learning methods could help to obtain which way more suit for some patients.MethodsData from consecutive ischaemic stroke patients with gastrointestinal haemorrhage were prospectively collected. The outcome was a recurrent stroke rate, haemorrhage events, mortality and favourable functional outcome (FFO). We analysed the data using conventional logistic regression methods and a supervised machine learning model. We used unsupervised machine learning to group and analyse data characters. ResultsThe patients of stopping antiplatelet drugs had a lower rate of bleeding events (p = 0.125), mortality (p = 0.008), rate of recurrence of stroke (p = 0.161) and distribution of severe patients (mRS 3–6) (p = 0.056). For Logistic regression, stopping antiplatelet drugs (OR = 2.826, p = 0.030) was related to lower mortality. The stopping antiplatelet drugs in the supervised machine learning model related to mortality (AUC = 0.95) and FFO (AUC = 0.82). For group by unsupervised machine learning, the patients of better prognosis had more male (p < 0.001), younger (p < 0.001), had lower NIHSS score (p < 0.001); and had a higher value of serum lipid level (p < 0.001).ConclusionsFor ischemic stroke patients with gastrointestinal haemorrhage, stopping antiplatelet drugs had a better prognosis. Patients who were younger, male, with lesser NIHSS scores at admission, with the fewest history of a medical, higher value of diastolic blood pressure, platelet, blood lipid and lower INR could have a better prognosis.

OC 45.3 Major Bleeding Event Rates in Patients on Hemodialysis and Peritoneal Dialysis: Results from the International DOPPS and PDOPPS

OC 45.3 Major Bleeding Event Rates in Patients on Hemodialysis and Peritoneal Dialysis: Results from the International DOPPS and PDOPPS

Risk Factors for Thromboembolic and Bleeding Events in Patients After the Fontan Operation (Insights from the National Database of Health Insurance Claims of Japan)

Risk stratification of thromboembolic events (TEs) and bleeding events is important for the appropriate selection of thromboprophylaxis in patients after the Fontan operation. Therefore, we clarified the risk factors for TEs and bleeding events in patients after the Fontan operation using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. We conducted a retrospective cohort study including 2,515 patients who underwent the Fontan operation between June 2011 and September 2019. The end points were TEs and bleeding events within 1year of the Fontan operation analysis. We analyzed the risk factors for these end points using a multivariate analysis. In total, 1,903 patients were included in the analysis. The median age at the time of the Fontan operation was 3 (1 to 22) years, and 1,067 patients (56%) were male. The incidence rates of TEs and bleeding events were 12% and 11%, respectively. Age (odds ratio [OR] 1.1 per 1 year older, p <0.05) was an independent risk factor for TEs. Thromboprophylaxis with aspirin after the Fontan operation significantly reduced TEs (OR 0.3, p <0.05). A history of postoperative hemorrhage (OR 1.5, p <0.05) and the use of a potassium channel blocker (OR 2.1, p <0.05) were independent risk factors for bleeding events. In conclusion, aspirin was found to reduce the risk of TEs within 1 year of the Fontan operation. The results of this study will be useful in selecting effective and safe thromboprophylaxis in patients after the Fontan operation.

Comparisons of drug-eluting balloon versus drug-eluting stent for the treatment of cancer patients presenting with acute myocardial infarction

BackgroundTreatment for cancer patients presenting with acute myocardial infarction (AMI) remains challenging. The objective of the study was to investigate the safety and efficiency of drug eluting balloon (DEB) versus drug eluting stent (DES) in this high-risk group.MethodsBetween 1st January 2017 and 1st January 2022, cancer patients admitted to Beijing Chaoyang Hospital with AMI were retrospectively enrolled. The primary endpoint was major adverse cardiovascular event (MACE). The secondary endpoints included major bleeding events, heart failure and cardiac complications.ResultsA total of 164 cancer patients presenting with AMI were included in the final analysis. Patients treated with DEB had a numerically lower rate of MACE than those treated with DES during a median follow-up of 21.8 months (22.9% vs. 37.1%, p = 0.23). Patients treated with DEB had a trend towards lower rate of major bleeding events than patients treated with DES (6.3% vs. 18.1%, HR 2.96, 95% CI [0.88, 9.92], p = 0.08). There were no significant differences between the two groups with regards to the rate of heart failure (4.2% vs. 9.5%, p = 0.32) and cardiac complications (0.0% vs. 2.6%, p = 0.56).ConclusionsThe present study demonstrated that in cancer patients with AMI, DEB had a trend towards lower rate of major bleeding events and a numerically lower rate of MACE compared with DES.Graphical

Anticoagulation strategies in COVID-19 infected patients receiving ECMO support.

Hospitalized COVID-19 patients with hypoxemic respiratory failure may deteriorate despite invasive mechanical ventilation and thus require extracorporeal membrane oxygenation (ECMO) support. Unfractionated heparin (UFH) is the antithrombotic of choice, however, bivalirudin may offer more predictable pharmacokinetics resulting in consistent anticoagulant effects with lower bleeding and thrombotic occurrences. The aim of this study was to evaluate efficacy and safety outcomes in patients undergoing venovenous (VV) ECMO receiving bivalirudin or UFH-based anticoagulation. This retrospective, single-center, observational cohort study included patients with confirmed COVID-19 infection requiring VV ECMO support receiving anticoagulation with UFH or bivalirudin. Primary endpoints were time to reach therapeutic aPTT, percent time spent in aPTT range, and the occurrence of thrombotic events over the entire course of ECMO support. Secondary endpoints included the incidence of major/minor bleeding, the ability to wean off ECMO support, in-hospital mortality, and length of stay. Twenty-two patients were included in the study (n=10 UFH, n=12 bivalirudin). Time to therapeutic aPTT was achieved faster with UFH (10h vs. 20h). The percentage time spent within the goal aPTT range was similar between UFH and bivalirudin (50% vs. 52%). Thrombotic events were significantly higher in the UFH group (40% DVT, 40% PE, 80% oxygenator thrombus in ECMO machine, 10% ischemic stroke) versus bivalirudin (8% DVT, 17% PE, 33% oxygenator thrombus, no ischemic strokes) (CI 95%, p=0.04). The overall bleeding incidence was higher in the UFH arm (90% vs. 75%). The mortality rate was 90% in the UFH group and 58% in the bivalirudin group. The length of stay was similar between the two study arms. In hospitalized patients with COVID-19-associated acute respiratory distress syndrome (ARDS) on VV ECMO support, the use of bivalirudin showed to be a viable anticoagulation alternative in terms of efficacy compared to UFH and resulted in a favorable safety profile with lower rates of bleeding and thrombotic events.

Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study.

Guidelines recommend extended dual antiplatelet therapy (DAPT), including ticagrelor 60mg twice daily, in high-risk post myocardial infarction (MI) patients who have tolerated 12 months and are not at high bleeding risk. The real-world utilization and bleeding and ischemic outcomes associated with long-term ticagrelor 60mg in routine clinical practice have not been well described. Register and claims data from US (Optum Clinformatics, IBM MarketScan, Medicare) and Europe (Sweden, Italy, UK, Germany) were extracted. Patients initiating ticagrelor 60mg≥12 months after MI, meeting eligibility criteria for PEGASUS-TIMI 54 trial, were included. The cumulative incidence of the composite of MI, stroke, or all-cause mortality, and of bleeding requiring hospitalization were calculated. Meta-analyses were performed to combine estimates from each source. 7035 patients treated with ticagrelor 60mg met eligibility criteria. Median age was 67 years and 29% were females; 12% had a history of multiple MIs. The majority (95%) had been treated with ticagrelor 90mg prior to initiating ticagrelor 60mg. At 12 months from initiation of ticagrelor 60mg, the cumulative incidence (95% CI) of MI, stroke or mortality was 3.33% (2.73-4.04) and was approximately three-fold the risk of bleeding (0.96%; 0.69-1.33). This study provides insights into the use of ticagrelor 60mg in patients with prior MI in clinical practice. Observed event rates for ischemic events and bleeding generally align with those in the pivotal trials, support the established safety profile of ticagrelor, and highlight the significant residual ischemic risk in this population.Clinical Trials.gov Registration NCT04568083.

Sex discrepancies in pathophysiology, presentation, treatment, and outcomes of severe aortic stenosis.

This review gives an overview of sex-based differences in aortic valve stenosis, spanning from pathophysiological mechanisms and disease progression, clinical presentation, presence of comorbidities, and diagnostic assessment, to treatment and outcomes. In particular, sex-related differences in the degree of aortic valve calcification, the response of the left ventricle to pressure overload, as well as in the referral to procedures, with women being less frequently referred for surgical aortic valve replacement and experiencing longer waiting times for transcatheter procedures, will be discussed. Sex-related differences are also particularly evident in outcomes of patients with severe aortic stenosis undergoing surgical or transcatheter procedures. The apparent sex paradox seen in women undergoing transcatheter aortic valve implantation refers to the phenomenon of women experiencing higher rates of short-term mortality and bleeding events, but demonstrating improved long-term survival as compared to men. Women who undergo surgical aortic valve replacement have generally worse outcomes as compared to men, which is reflected by the inclusion of female sex in surgical risk calculation scores. Hence, a thorough understanding of sex-related differences in aortic valve stenosis is important to provide optimal and personalized patient care.

Edoxaban use in the context of dental procedures: analysis from the EMIT-AF/VTE database

IntroductionLiterature reviews support continuing anticoagulation during dental procedures. However, studies often present grouped anticoagulation data, and information on individual anticoagulant management would be helpful to dentists. The Edoxaban Management in Diagnostic and Therapeutic Procedures (EMIT-AF/VTE) programme (NCT02950168; NCT02951039) demonstrated low periprocedural bleeding and thrombotic event rates in patients with atrial fibrillation receiving edoxaban.AimsTo report periprocedural edoxaban interruption and clinical events in patients from EMIT-AF/VTE who underwent dental procedures.MethodsDental procedures were categorised by type (cleaning/noncleaning). Edoxaban interruption, bleeding events, and thrombotic events were observed 5 days preprocedure through 29 days postprocedure.ResultsOverall, 196 patients underwent 350 cleaning and/or noncleaning procedures; most patients (171/196 [87.2%]) underwent noncleaning procedures (282/350 [80.6%]), whereas 48/196 (24.5%) underwent 68/350 (19.4%) cleaning procedures. Edoxaban was uninterrupted for most cleanings (53/68 [77.9%]). Preprocedural interruption was common for single and multiple tooth extractions (single, 67/100 [67.0%]; multiple, 16/30 [53.3%]). The only major bleeding occurred after an unrelated cleaning. Minor bleeding occurred in 1/68 (1.5%) cleaning and 4/282 (1.4%) noncleaning procedures. There were no thrombotic events.ConclusionsFor most cleanings, edoxaban was not interrupted, whereas preprocedural interruption was more common for tooth extractions. Overall, bleeding rates were low, and no thrombotic events occurred.

Less major bleeding and higher hemoglobin after left atrial appendage closure in high-risk patients: Data from a long-term, longitudinal, two-center observational study.

Left atrial appendage closure (LAAC) is a mechanical alternative for stroke prevention in patients at risk who cannot tolerate oral anticoagulation (OAC). Our hypothesis was that the reduction of anticoagulation following LAAC results in a decrease of bleeding events and a rise in serum hemoglobin in a high-risk collective of patients with atrial fibrillation (AF). Bleeding events, use of erythrocyte concentrates, anticoagulation, embolic events, and serum hemoglobin levels before and following LAAC were compared over more than 4 years. Seventy-five patients (CHA₂DS₂-VASc score 4.4 ± 1.7, HAS-BLED score 4.6 ± 1.1) were analyzed. Before LAAC (observation period 1.8 ± 1.8 years), 67 patients experienced 1.8 ± 1.4 bleeding events (0.9 ± 1.3 major) per year resulting in 0.7 ± 1.3 transfusions per year. After LAAC (2.6 ± 2.0 years), 26 patients (p < .0001 vs. before) had 0.6 ± 2.1 bleeding events (p < .0001), 0.2 ± 0.6 major bleedings (p < .0001) and received 0.6 ± 1.9 transfusions per year (p = .671). Fourteen patients had stroke before and 3 after LAAC (p = .008). Serum hemoglobin increased from initially 9.9 ± 3.0to 11.9 ± 2.3 g/dL until the end of follow-up (p = .0005). Adverse embolic events did not differ before and after LAAC in our collective. In this clinical relevant cohort of AF patients with high risk for stroke and intolerance to OAC, we show that LAAC was able to reduce the rate of stroke and bleeding events, which translated into a rising serum hemoglobin concentration.

5-year stroke rates in nonvalvular atrial fibrillation after watchman compared to direct oral anticoagulants

BackgroundThe WATCHMAN device (Boston Scientific; Marlborough, MA, USA) is noninferior to warfarin in preventing ischemic strokes while reducing bleeding risks associated with long term anticoagulation in nonvalvular atrial fibrillation (AFib). The device's performance compared to direct oral anticoagulants (DOAC) is less well known. ObjectiveTo compare 5-year major bleeding and ischemic stroke rates in patients with nonvalvular AFib who received a WATCHMAN device or DOAC therapy after a major bleeding event. MethodsThis retrospective, multicenter, 1:1 matched cohort study was derived from the PearlDiver Mariner database from 2010 to 2020. Patients with nonvalvular AFib on oral anticoagulation who had a major bleeding event were identified. Those who received either WATCHMAN or DOAC after resolution of the bleeding event were selected. The two groups were exactly matched 1:1 based on various comorbidities. Rates of ischemic stroke, transient ischemic attack (TIA), major bleeding, and hemorrhagic stroke were compared over 5 years. ResultsEach cohort consisted of 2248 patients after 1:1 matching. The mean CHADS2-VASC score was 4.81 ± 1.25. At 5 years, the WATCHMAN cohort had significantly lower rates of major bleeding events [OR 0.24 (0.21, 0.27)], TIAs [OR 0.75 (0.58, 0.95)], and ischemic strokes [OR 0.72 (0.61, 0.86)]. There was no significant difference in hemorrhagic strokes [OR 1.14 (0.83, 1.58)]. ConclusionEven in a high-risk population, the WATCHMAN is comparable to DOAC therapy in the primary prevention of hemorrhagic strokes and may provide benefit in the rates of bleeding events, TIAs, and ischemic strokes.

Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis.

Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to aspirin for primary thromboprophylaxis in this population, but data comparing these two therapies are limited. We performed a systematic review and meta-analysis to compare DOACs with aspirin for primary thromboprophylaxis in individuals undergoing outpatient anti-myeloma therapy. Studies were selected when comparing DOACs versus aspirin for thrombotic and haemorrhagic outcomes. We included 10 randomised controlled trials and observational studies comprising 1026 patients with MM who received primary thromboprophylaxis with DOACs (n = 337) or aspirin (n = 689). DOAC thromboprophylaxis was associated with a significantly lower incidence of VTE compared with aspirin (OR 0.33; 95% CI 0.16-0.68; p < 0.001). Major, clinically relevant non-major and minor bleeding event rates did not differ significantly between groups. Overall, our meta-analysis suggests that DOACs may be a preferable option to aspirin for the prevention of MM-related thrombosis. However, these results should be interpreted in the context of heterogeneous baseline population characteristics and potential bias from including observational studies. Further research is needed to evaluate the optimal thromboprophylaxis strategy, particularly in high-risk individuals.

Treatment of post-tonsillectomy hemorrhage with nebulized tranexamic acid: A retrospective study.

To evaluate the association of treatment with nebulized tranexamic acid (TXA) with rates of operative intervention in post-tonsillectomy hemorrhage (PTH). Single tertiary-referral center and satellite hospitals, retrospective cohort of adult and pediatric patients who were diagnosed with PTH in 2015-2022 and treated with nebulized TXA and standard care, compared with an age- and gender-matched control cohort treated with standard care. Patients were typically treated in the emergency department with a single dose of 500mg/5mL TXA delivered via nebulizer. 1110 total cases of PTH were observed, and 83 were treated with nebulized TXA. Compared to 249 age- and gender-matched PTH controls, TXA-treated patients had a rate of operating room (OR) intervention of 36.1% versus 60.2% (p<0.0001) and a rate of repeat bleeding of 4.9% versus 14.2% (p<0.02). The odds ratio for OR intervention with TXA treatment was 0.37 (95% CI 0.22, 0.63). There were no adverse effects identified with an average follow-up time of 586 days. Treatment of PTH with nebulized TXA is associated with lower rates of operative intervention and lower rates of repeat bleeding events. Prospective studies are needed to further characterize efficacy and optimal treatment protocols.

Single center evaluation on the use of conditionally ordered low molecular weight heparins in malignant hematology patients with venous thromboembolism.

Cancer and cancer-related treatments are significant independent risk factors for malignant hematology (MH) patients in developing venous thromboembolism (VTE). Treatment of VTE in MH patients at the Princess Margaret Cancer Centre is predominantly initiated with low molecular weight heparin (LMWH) in accordance with guidelines. While guidelines recommend against LMWH use in patients with thrombocytopenia, prescribers may order LMWH conditionally based on platelet values. Currently, there is a lack of consistent practice with variation in both the use of conditional orders as well as the threshold of platelet values for conditional orders. The objectives of the study were to (a) describe the use of conditionally ordered LMWH based on platelet values; (b) determine its safety by measuring administration concordance with conditional orders and bleeding event rates during inpatient admission; and (c) determine its efficacy by measuring the rate of worsening VTE or recurrence during inpatient admission. Electronic records of MH inpatients admitted between January 2017 and December 2019 and who were administered at least one dose of an LMWH for the treatment of VTE were screened. One hundred and eight patients were screened to obtain 50 eligible patients with a median age of 59 years (SD = ±18.8 years). The most frequent MH diagnosis was acute lymphoblastic leukemia (30%). Sixty percent (n = 30) of patients received conditional orders. Out of 571 administrations, 543 (95%) were administered concordantly (Χ2(1) = 472, p < 0.0001). In this group of patients, 8 patients had either documented bleeding or experienced a drop in hemoglobin >10 g/L within a 72 h time frame. No patients experienced a recurrent VTE during inpatient treatment (for up to 40 days post-admission). It appears that conditionally ordered LMWH can be concordantly administered and is safe and effective in the treatment of VTE in MH patients experiencing thrombocytopenia. There were no reports of worsening or new VTE in our small sample.