Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment.

OBJECTIVE: To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide. MATERIALS AND METHODS: The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators. RESULTS: Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered. CONCLUSION: The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.

An Aspirin-Free Strategy for Immediate Treatment Following Complex Percutaneous Coronary Intervention.

BACKGROUND: There was no study evaluating the effects of an aspirin-free strategy in patients undergoing complex percutaneous coronary intervention (PCI). OBJECTIVES: The authors aimed to evaluate the efficacy and safety of an aspirin-free strategy in patients undergoing complex PCI. METHODS: We conducted the prespecified subgroup analysis based on complex PCI in the STOPDAPT-3 (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3), which randomly compared low-dose prasugrel (3.75 mg/d) monotherapy to dual antiplatelet therapy (DAPT) with low-dose prasugrel and aspirin in patients with acute coronary syndrome or high bleeding risk. Complex PCI was defined as any of the following 6 criteria: 3 vessels treated, ≥3 stents implanted, ≥3 lesions treated, bifurcation with 2 stents implanted, total stent length >60 mm, or a target of chronic total occlusion. The coprimary endpoints were major bleeding events (Bleeding Academic Research Consortium 3 or 5) and cardiovascular events (a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke) at 1 month. RESULTS: Of the 5,966 study patients, there were 1,230 patients (20.6%) with complex PCI. Regardless of complex PCI, the effects of no aspirin relative to DAPT were not significant for the coprimary bleeding (complex PCI: 5.30% vs 3.70%; HR: 1.44; 95% CI: 0.84-2.47; P = 0.18 and noncomplex PCI: 4.26% vs 4.97%; HR: 0.85; 95% CI: 0.65-1.11; P = 0.24; P for interaction = 0.08) and cardiovascular (complex PCI: 5.78% vs 5.93%; HR: 0.98; 95% CI: 0.62-1.55; P = 0.92 and noncomplex PCI: 3.70% vs 3.10%; HR: 1.20; 95% CI: 0.88-1.63; P = 0.25; P for interaction = 0.48) endpoints without significant interactions. CONCLUSIONS: The effects of the aspirin-free strategy relative to standard DAPT for the cardiovascular and major bleeding events were not different regardless of complex PCI. (ShorT and OPtimal duration of Dual AntiPlatelet Therapy after everolimus-eluting cobalt-chromium stent-3 [STOPDAPT-3]; NCT04609111).

Direct Oral Anticoagulation in Lung Transplant Recipients.

OBJECTIVES: Presently, the management of direct oral anticoagulants lacks specific guidelines for patients before and after transplant, particularly for lung transplant recipients. We aimed to consolidate the existing literature on direct oral anticoagulants and explore their implications in lung transplant recipients. MATERIALS AND METHODS: We conducted a comprehensive search in PubMed and Google Scholar databases for studies published between January 2000 and December 2022, using specific search terms. We only included studies involving lung transplant recipients and focusing on direct oral anticoagulants. RESULTS: Five relevant publications were identified, providing varied insights. None of the studies specifically addressed bleeding complications associated with direct oral anticoagulants in lung transplant recipients. Limited details were available on the type of solid-organ transplant or the specific direct oral anticoagulant used in these studies. CONCLUSIONS: Varied bleeding complications associated with direct oral anticoagulants in lung transplant recipients were reported, but studies lacked specificity on transplant type and direct oral anticoagulant variations. Notably, the incidence of venous thrombotic embolism in lung transplant recipients was comparatively higher than in other solid-organ transplant recipients, potentially linked to factors such as corticosteroid therapy, calcineurin inhibitors, and cytomegalovirus infections. Our synthesis on findings of use of direct oral anticoagulant in lung transplant recipients emphasized challenges of managing these medications in urgent transplant situations. Recommendations from experts suggested caution in initiation of direct oral anticoagulants posttransplant until stability in renal and hepatic function is achieved. The limited evidence on safety of direct oral anticoagulants in lung transplant recipients underscores the need for further research and guidance in this specific patient population.

Predictors of adherence to direct oral anticoagulants after cardiovascular or bleeding events in Medicare Advantage Plan enrollees with atrial fibrillation.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended for patients with atrial fibrillation (AF) given their improved safety profile. Suboptimal adherence to DOACs remains a significant concern among individuals with AF. However, the extent of adherence to DOACs following a cardiovascular or bleeding event has not been fully evaluated. OBJECTIVE: To evaluate the pattern of adherence trajectories of DOACs after a cardiovascular or bleeding event and to investigate the sociodemographic and clinical predictors associated with each adherence trajectory by using claims-based data. METHODS: This retrospective study was conducted among patients with AF prescribed with DOACs (dabigatran/apixaban/rivaroxaban) between July 2016 and December 2017 and who were continuously enrolled in the Texas-based Medicare Advantage Plan. Patients who experienced a cardiovascular or bleeding event while using the DOACs were further included in the analysis. The sample was limited to patients who experienced a clinical event such as a cardiovascular or bleeding event while using the DOACs. The clinical events considered in this study were cardiovascular (stroke, congestive heart failure, myocardial infarction, systemic embolism) and bleeding events. To assess adherence patterns, each patient with a DOAC prescription was followed up for a year after experiencing a clinical event. The monthly adherence to DOACs after these events was evaluated using the proportion of days covered (PDC). A group-based trajectory model incorporated the monthly PDC to classify groups of patients based on their distinct patterns of adherence. Predictors associated with each trajectory were assessed using a multinomial logistic regression model, with the adherent trajectory serving as the reference group in the outcome variable. RESULTS: Among the 694 patients with AF who experienced clinical events after the initiation of DOACs, 3 distinct adherence trajectories were identified: intermediate nonadherent (30.50%), adherent (37.7%), and low adherent (31.8%); the mean PDC was 0.47 for the intermediate nonadherent trajectory, 0.93 for the adherent trajectory, and 0.01 for low adherent trajectory. The low-income subsidy was significantly associated with lower adherence trajectories (odds ratio [OR] = 4.81; 95% CI = 3.07-7.51) and with intermediate nonadherent trajectories (OR = 1.57; 95% CI = 1.06-2.34). Also, nonsteroidal anti-inflammatory drug use was significantly associated with lower adherence trajectories (OR = 5.10; 95% CI = 1.95-13.36) and intermediate nonadherent trajectories (OR = 3.17; 95% CI = 1.26-7.93). Other predictors significantly associated with both nonadherent trajectories are type of DOACs (OR = 0.53; 95% CI = 0.35-0.79), presence of coronary artery disease (OR = 1.89; 95% CI = 1.01-3.55), and having 2 or more clinical events (OR = 1.65; 95% CI = 1.09-2.50). CONCLUSIONS: Predictors identified provide valuable insights into the suboptimal adherence of DOACs among Medicare Advantage Plan enrollees with AF, which can guide the development of targeted interventions to enhance adherence in this high-risk patient population.

Engineering and evaluation of FXa bypassing agents that restore hemostasis following Apixaban associated bleeding.

Direct oral anticoagulants (DOACs) targeting activated factor Xa (FXa) are used to prevent or treat thromboembolic disorders. DOACs reversibly bind to FXa and inhibit its enzymatic activity. However, DOAC treatment carries the risk of anticoagulant-associated bleeding. Currently, only one specific agent, andexanet alfa, is approved to reverse the anticoagulant effects of FXa-targeting DOACs (FXaDOACs) and control life-threatening bleeding. However, because of its mechanism of action, andexanet alfa requires a cumbersome dosing schedule, and its use is associated with the risk of thrombosis. Here, we present the computational design, engineering, and evaluation of FXa-variants that exhibit anticoagulation reversal activity in the presence of FXaDOACs. Our designs demonstrate low DOAC binding affinity, retain FXa-enzymatic activity and reduce the DOAC-associated bleeding by restoring hemostasis in mice treated with apixaban. Importantly, the FXaDOACs reversal agents we designed, unlike andexanet alfa, do not inhibit TFPI, and consequently, may have a safer thrombogenic profile.

Perioperative Management in Patients with Atrial Fibrillation Treated with Non-Vitamin K Antagonist Oral Anticoagulants Undergoing Minor Bleeding Risk Procedure: Rationale and Protocol for the PERIXa Study.

Background: While treatment interruption of non-vitamin K antagonist oral anticoagulants (NOACs) for elective surgery or procedures among patients with atrial fibrillation (AF) is becoming more prevalent, there remains insufficient evidence regarding the optimal perioperative management of NOACs, particularly procedures with minor bleeding risks. Objective: This study aims to evaluate the safety and effectiveness of a simplified, standardized protocol for perioperative management of direct factor Xa inhibitors in patients, with AF undergoing procedures associated with minor bleeding risk. Methods: This multicenter, prospective single-arm registry study plans to enroll patients undergoing procedures with minor bleeding risk who were prescribed direct factor Xa inhibitors for AF. The procedures with minor bleeding risk will include gastrointestinal endoscopy for diagnostic purposes, selected dental procedures, and ocular surgery for cataracts or glaucoma. For apixaban, patients will withhold the last evening dose and resume either from the evening dose of the procedure day or the following morning, depending on the bleeding risk of the patient. For edoxaban or rivaroxaban, patients will withhold only a single dose on the procedure day. The primary outcome is the occurrence of major bleeding events within 30 days. Secondary outcomes include systemic thromboembolism, all-cause mortality, and a composite of major and clinically relevant non-major bleeding events. Conclusion: This study has the potential to generate evidence regarding the safety of perioperative management for patients, with AF undergoing procedures associated with minor bleeding risk. Trial Registration: Clinicaltrials.gov: NCT05801068.

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany.

OBJECTIVE: To verify the incidence of bleeding events in patients on ongoing anticoagulant treatment in the real world and compare the results of different reversal or repletion strategies currently available for pharmacological treatment. METHODS: Patients managed in the emergency department (ED) with major bleeding events, on ongoing anticoagulation were stratified according to bleeding site and reversal or repletion therapy with andexanet alfa (ADX), idarucizumab (IDA), prothrombin complex concentrate (PCC), and vitamin K (Vit-K). ENDPOINT: Death at 30 days was compared in the subgroups with cerebral hemorrhage (CH) and gastrointestinal (GI) bleeding. RESULTS: Of the 809,397 visits in the years 2022-2023 at 6 EDs in the northwestern health district of Tuscany, 5372 patients with bleeding events were considered; 3740 were excluded due to minor bleeding or propensity score matching. Of the remaining 1632 patients with major bleeding, 548 on ongoing anticoagulation were enrolled; 334 received reversal or repletion agents. Patients with CH (n = 176) and GI bleeding (n = 108) represented the primary analysis cohorts in the study's strategic treatment assessment. Overall, 30-day survival of patients on ongoing aFXa treatment receiving on-label ADX versus off-label PCC showed a relative increase of 71%, while 30-day survival of patients on ongoing aFII receiving on-label IDA versus off-label PCC showed a relative increase of 30%; no substantial difference was found when comparing on-label PCC combined with Vit-K versus off-label Vit-K alone. Indeed, patients undergoing on-label ADX or IDA showed a statistically significant difference over off-label PCC (ADX vs. PCC: n = 15, events = 4, mean ± SD 82.50 ± 18.9, vs. 49, 13, 98.82 ± 27, respectively; analysis of variance [ANOVA] variance 8627; P < 0.001; posthoc test diff 32, 95% confidence interval: 28-35; P < 001; IDA vs. PCC: 20, 5, 32.29 ± 15.0 vs. 2, 1, 28.00 ± 0.0, respectively; ANOVA 1484; P < 0.001; posthoc test -29, -29 -29, respectively; P = n.d.). On-label PCC combined with Vit-K showed overall a slight statistically significant difference versus off-label Vit-K alone (52, 16, 100.58 ± 22.6 vs. 53, 11, 154.62 ± 29.8, respectively; ANOVA 310; P < 0.02; posthoc test 4, 0.7-7.2, respectively; P < 0.02). Data were confirmed in the group of patients with CH (ADX vs. PCC: n = 13, events = 3, mean ± SD 91.55 ± 18.6 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA variance 10,091, F = 261; P < 0.001; posthoc difference test 36, 95% confidence interval: 30-41; P < 0.001; IDA vs. PCC: 10, 2, 4.50 ± 2.5 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA 16,876,303, respectively; P < 0.001; posthoc test 41, 34-47, respectively; P < 0.001). On-label PCC combined with Vit-K showed an overall slight statistically significant difference compared with off-label Vit-K alone (P < 0.01 and P < 0.001 in the subgroups of CH and GI bleeding). CONCLUSIONS: Patients undergoing specific reversal therapy with on-label ADX or IDA, when treated with aFXa or aFII anticoagulants, respectively, showed statistically elevated differences in 30-day death compared with off-label repletion therapy with PCC. Overall, 30-day survival of patients on ongoing aFXa or aFII receiving on-label reversal therapy with ADX or IDA compared with off-label PCC repletion agents showed an increase of 71% and 30%, respectively.

Emicizumab prophylaxis in people with hemophilia A and inhibitors: a systematic review and meta-analysis.

BACKGROUND: Until recently, the treatment of people with hemophilia A and inhibitors (PwHAi) was based on the use of bypassing agents (BPA). However, the advent of emicizumab as prophylaxis has demonstrated promising results. OBJECTIVES: We aimed to compare the bleeding endpoints between PwHAi on BPA and those on emicizumab prophylaxis. DESIGN AND SETTING: Systematic review of interventions and meta-analysis conducted at the Universidade Federal de Goiás, Goiânia, Goiás, Brazil. METHODS: The CENTRAL, MEDLINE, Scopus, and LILACS databases were searched on February 21, 2023. Two authors conducted the literature search, publication selection, and data extraction. The selected publications evaluated the bleeding endpoints between PwHAi on emicizumab prophylaxis and those on BPA prophylaxis. The risk of bias was evaluated according to the Joanna Briggs Institute criteria. A meta-analysis was performed to determine the annualized bleeding rate (ABR) for treated bleeds. RESULTS: Five publications (56 PwHAi) were selected from the 543 retrieved records. Overall, bleeding endpoints were lower during emicizumab prophylaxis than during BPA prophylaxis. All the publications had at least one risk of bias. The only common parameter for the meta-analysis was the ABR for treated bleeds. During emicizumab prophylaxis, the ABR for treated bleeds was lower than during BPA prophylaxis (standard mean difference: -1.58; 95% confidence interval -2.50, -0.66, P = 0.0008; I2 = 68.4%, P = 0.0031). CONCLUSION: Emicizumab was superior to BPA in bleeding prophylaxis in PwHAi. However, both the small population size and potential risk of bias should be considered when evaluating these results. SYSTEMATIC REVIEW REGISTRATION: CRD42021278726, https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=278726.

Safety and efficacy of apixaban versus vitamin K antagonists in patients undergoing dialysis: a systematic review and meta-analysis.

BACKGROUND: This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis. METHODS: All types of studies published on PubMed, Embase, CENTRAL, and Web of Science up to 10 September 2023 and comparing outcomes of apixaban vs. VKA in dialysis patients were eligible. RESULTS: Two randomized controlled trials (RCTs) and six retrospective studies were included. Apixaban treatment was associated with significantly lower risk of major bleeding (RR: 0.61; 95% CI: 0.48, 0.77; I2 = 50%) and clinically relevant non-major bleeding (RR: 0.82, 95% CI: 0.68, 0.98, I2 = 9%) compared to VKA. Meta-analysis also showed that the risk of gastrointestinal bleeding (RR: 0.74, 95% CI: 0.64, 0.85, I2 = 16%) and intracranial bleeding (RR: 0.64, 95% CI: 0.49, 0.84, I2 = 0%) was significantly reduced with apixaban. Meta-analysis showed no difference in the risk of ischemic stroke (RR: 0.40, 95% CI: 0.06, 2.69, I2 = 0%), mortality (RR: 1.26, 95% CI: 0.74, 2.16, I2 = 94%) and recurrent venous thromboembolism (RR: 1.02, 95% CI: 0.87, 1.21, I2 = 0%) between the two groups. Subgroup analysis of RCTs showed no difference in bleeding outcomes. CONCLUSIONS: Low-quality evidence from a mix of RCTs and retrospective studies shows that apixaban may have better safety and equivalent efficacy as compared to VKA in dialysis patients. Apixaban treatment correlated with significantly reduced risk of major bleeding and clinically relevant nonmajor bleeding in observational studies but not in RCTs. The predominance of retrospective data warrants caution in the interpretation of results.

One- versus three-month dual antiplatelet therapy in high bleeding risk patients undergoing percutaneous coronary intervention for non-ST-segment elevation acute coronary syndromes.

BACKGROUND: A short dual antiplatelet therapy (DAPT) duration has been proposed for patients at high bleeding risk (HBR) undergoing drug-eluting coronary stent (DES) implantation. Whether this strategy is safe and effective after a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains uncertain. AIMS: We aimed to compare the impact of 1-month versus 3-month DAPT on clinical outcomes after DES implantation among HBR patients with or without NSTE-ACS. METHODS: This is a prespecified analysis from the XIENCE Short DAPT programme involving three prospective, international, single-arm studies evaluating the safety and efficacy of 1-month (XIENCE 28 USA and Global) or 3-month (XIENCE 90) DAPT among HBR patients after implantation of a cobalt-chromium everolimus-eluting stent. Ischaemic and bleeding outcomes associated with 1- versus 3-month DAPT were assessed according to clinical presentation using propensity score stratification. RESULTS: Of 3,364 HBR patients (1,392 on 1-month DAPT and 1,972 on 3-month DAPT), 1,164 (34.6%) underwent DES implantation for NSTE-ACS. At 12 months, the risk of the primary endpoint of death or myocardial infarction was similar between 1- and 3-month DAPT in patients with (hazard ratio [HR] 1.09, 95% confidence interval [CI]: 0.71-1.65) and without NSTE-ACS (HR 0.88, 95% CI: 0.63-1.23; p-interaction=0.34). The key secondary endpoint of Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding was consistently reduced in both NSTE-ACS (HR 0.57, 95% CI: 0.37-0.88) and stable patients (HR 0.84, 95% CI: 0.61-1.15; p-interaction=0.15) with 1-month DAPT. CONCLUSIONS: Among HBR patients undergoing implantation of an everolimus-eluting stent, 1-month, compared to 3-month DAPT, was associated with similar ischaemic risk and reduced bleeding at 1 year, irrespective of clinical presentation.

Study Design of a Brazilian Observational Study of Edoxaban in Patients with Atrial Fibrillation (EdoBRA). / Desenho de Estudo de um Estudo Observacional Brasileiro sobre o uso de Edoxabana em Pacientes com Fibrilação Atrial (EdoBRA).

BACKGROUND: Clinical trials showed the safety of Edoxaban, a non-vitamin K-dependent oral anticoagulant (NOAC), and its efficacy to prevent stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients and also to prevent and treat venous thromboembolism. However, additional research is needed to evaluate the safety and effectiveness of Edoxaban in a real-world scenario in the Brazilian population. OBJECTIVE: In order to understand the risks and benefits of Edoxaban use in routine clinical settings, the EdoBRA study is being conducted to gain insight into the safety and effectiveness of Edoxaban use in non-preselected patients with NVAF in Brazil. METHODS: The EdoBRA study is a multicenter, prospective, observational study conducted in 36 sites in Brazil. NVAF patients ≥ 18 years treated with commercially available Edoxaban who initiated treatment for at least 14 days and no longer than 90 days prior to enrollment, and who are not simultaneously participating in any interventional study are eligible for this study. Seven hundred patients are planned to be enrolled and one-year of follow up, with data collections expected at baseline and 3, 6, and 12 months after the study enrollment. The primary safety objective is ISTH Clinically Relevant Bleeding, and the secondary effectiveness objective focuses on relevant cardiovascular outcomes related to NVAF. CONCLUSION: EdoBRA observational study will generate relevant additional information about NOAC Edoxaban on various aspects of patient management in routine care, such as its safety and effectiveness profile in patients with NVAF in Brazil.

FUNDAMENTO: Os ensaios clínicos demonstraram a segurança da Edoxabana, um anticoagulante oral não dependente de vitamina K (NOAC), e a sua eficácia na prevenção de acidente vascular cerebral e embolia sistémica em pacientes com fibrilação atrial não valvar (FANV) e também na prevenção e tratamento de tromboembolismo venoso. No entanto, pesquisas adicionais são necessárias para avaliar a segurança e a eficácia da Edoxabana em um cenário real na população brasileira. OBJETIVO: A fim de compreender os riscos e benefícios do uso da Edoxabana em cenários clínicos de rotina, o estudo EdoBRA está sendo conduzido para obter informações sobre a segurança e eficácia do uso da Edoxabana em pacientes não pré-selecionados com FANV no Brasil. MÉTODOS: O estudo EdoBRA é um estudo multicêntrico, prospectivo e observacional, realizado em 36 centros no Brasil. São elegíveis para este estudo pacientes com FANV, ≥ 18 anos de idade, tratados com Edoxabana disponível comercialmente, que iniciaram o tratamento por pelo menos 14 dias e não mais do que 90 dias antes da data de inclusão no estudo, e que não estão participando de nenhum outro estudo de intervenção. Ao todo, 700 pacientes devem ser inscritos e acompanhados por um ano, com coletas de dados programadas para o período basal e 3, 6 e 12 meses após a inscrição no estudo. O objetivo primário de segurança é o sangramento clinicamente relevante (de acordo com critérios da Sociedade Internacional de Trombose e Hemostasia - ISTH), e o objetivo secundário de eficácia são desfechos cardiovasculares relevantes relacionados à FANV. CONCLUSÃO: O estudo observacional EdoBRA gerará informações adicionais relevantes sobre a Edoxabana enquanto NOAC em diversos aspectos do manejo de pacientes no atendimento clínico de rotina, como perfil de segurança e efetividade em pacientes com FANV no Brasil.

New Score Models for Predicting Bleeding and Ischemic of Ticagrelor Therapy in Patients with Diabetes Mellitus.

PURPOSE: Ticagrelor is an antiplatelet drug, and its use increases the risk of bleeding. Coronary artery disease is significantly influenced by the widespread occurrence of diabetes mellitus. In order to decrease the incidence of clinical adverse events, a novel bleeding and thrombosis score is developed in this research. METHODS: We conducted a retrospective analysis of patient data from two medical centers who were diagnosed with diabetes mellitus and treated with ticagrelor. We gathered information on every patient from the electronic database of the hospital and follow-up. The collected data were statistically analyzed to obtain risk factors for bleeding and ischemic events. RESULTS: A total of 851 patients with diabetes mellitus who have been administered ticagrelor are included in our investigation. A total of 76 patients have bleeding events and 80 patients have ischemic events. The analysis of multiple variables indicates that characteristics like the age of >65, having a previous occurrence of bleeding, experiencing anemia, using aspirin, and taking atorvastatin are linked to a higher likelihood of bleeding. Additionally, the age of >65, smoking, having a history of blood clots, and having a BMI ≥ 30 are found to increase the risk of ischemia. CONCLUSION: The A4B score established in this study was better than the HAS-BLED score，and the same is true for the ABST score to the CHA2DS-VASc score. This new risk assessment model can potentially detect patients who are at high risk for bleeding and ischemic events. For high-risk patients, the dose of ticagrelor can be adjusted appropriately or the medication can be adjusted.(2023-09-11, ChiCTR2300075627).

In mild ischemic stroke or high-risk TIA, DAPT started ≤72 h after onset reduced new stroke and increased bleeding at 90 d.

SOURCE CITATION: Gao Y, Chen W, Pan Y, et al; INSPIRES Investigators. Dual antiplatelet treatment up to 72 hours after ischemic stroke. N Engl J Med. 2023;389:2413-2424. 38157499.

In older patients with AF and frailty, switching from VKA to NOAC therapy increased a composite of major or CRNM bleeding at 12 mo.

SOURCE CITATION: Joosten LP, van Doorn S, van de Ven PM, et al. Safety of switching from a vitamin K antagonist to a non-vitamin K antagonist oral anticoagulant in frail older patients with atrial fibrillation: results of the FRAIL-AF randomized controlled trial. Circulation. 2024;149:279-289. 37634130.

Safety and Efficacy of Direct Oral Anticoagulants vs Warfarin in Patients With Obesity and Venous Thromboembolism: A Retrospective Analysis.

BACKGROUND: Current venous thromboembolism guidelines recommend using direct oral anticoagulants (DOACs) over warfarin regardless of obesity status; however, evidence remains limited for the safety and efficacy of DOAC use in patients with obesity. This retrospective analysis sought to demonstrate the safety and efficacy of DOACs compared with warfarin in a diverse population of patients with obesity in light of current prescribing practices. METHODS: A retrospective cohort study was conducted at a large academic health system between July 2014 and September 2019. Adults with an admission diagnosis of deep vein thrombosis (DVT) or pulmonary embolism, with weight greater than 120 kg or a body mass index greater than 40, and who were discharged on an oral anticoagulant were included. Outcomes included occurrence of a thromboembolic event (DVT, pulmonary embolism, or ischemic stroke), bleeding event requiring hospitalization, and all-cause mortality within 12 months following index admission. RESULTS: Out of 787 patients included, 520 were in the DOAC group and 267 were in the warfarin group. Within 12 months of index hospitalization, thromboembolic events occurred in 4.23% of patients in the DOAC group vs 7.12% of patients in the warfarin group (hazard ratio, 0.6 [95% CI, 0.32-1.1]; P = .082). Bleeding events requiring hospitalization occurred in 8.85% of DOAC patients vs 10.1% of warfarin patients (hazard ratio, 0.93 [95% CI, 0.57-1.5]; P = .82). A DVT occurred in 1.7% and 4.9% of patients in the DOAC and warfarin groups, respectively (hazard ratio, 0.35 [95% CI, 0.15-0.84]; P = .046). CONCLUSION: No significant differences could be determined between DOACs and warfarin for cumulative thromboembolic or bleeding events, pulmonary embolism, ischemic stroke, or all-cause mortality. The risk of DVT was lower with apixaban and rivaroxaban. Regardless of patient weight or body mass index, physicians prescribed DOACs more commonly than warfarin.

Association of anti-factor Xa-guided anticoagulation with hemorrhage during ECMO support: A systematic review and meta-analysis.

BACKGROUND: The use of extracorporeal membrane oxygenation (ECMO) is associated with complex hemostatic changes. Systemic anticoagulation is initiated to prevent clotting in the ECMO system, but this comes with an increased risk of bleeding. Evidence on the use of anti-Xa-guided monitoring to prevent bleeding during ECMO support is limited. Therefore, we aimed to analyze the association between anti-factor Xa-guided anticoagulation and hemorrhage during ECMO. METHODS: A systematic review and meta-analysis was performed (up to August 2023). PROSPERO: CRD42023448888. RESULTS: Twenty-six studies comprising 2293 patients were included in the analysis, with six works being part of the meta-analysis. The mean anti-Xa values did not show a significant difference between patients with and without hemorrhage (standardized mean difference -0.05; 95% confidence interval [CI]: -0.19; 0.28, p = .69). We found a positive correlation between anti-Xa levels and unfractionated heparin dose (UFH; pooled estimate of correlation coefficients 0.44; 95% CI: 0.33; 0.55, p < .001). The most frequent complications were any type of hemorrhage (pooled 36%) and thrombosis (33%). Nearly half of the critically ill patients did not survive to hospital discharge (47%). CONCLUSIONS: The most appropriate tool for anticoagulation monitoring in ECMO patients is uncertain. Our analysis did not reveal a significant difference in anti-Xa levels in patients with and without hemorrhagic events. However, we found a moderate correlation between anti-Xa and the UFH dose, supporting its utilization in monitoring UFH anticoagulation. Given the limitations of time-guided monitoring methods, the role of anti-Xa is promising and further research is warranted.

Obese patients with atrial fibrillation are more efficiently protected from thrombosis under warfarin or xabans compared to non-obese patients; a systematic review and Meta-analysis of six randomized controlled trials.

INTRODUCTION: Recommendations about proper anticoagulation in obese patients, body mass index (BMI) > 30 kg/m2, are not yet clearly defined. Obese patients were included in randomized controlled trials comparing new anticoagulants (NOACs) with warfarin in patients with atrial fibrillation or thromboembolism. METHODS: We performed a medline search entering proper criteria and finally 6 post-hoc analysis of RCTs, reporting outcome according to BMI, were included in this meta-analysis. Two major outcomes were considered end points in our meta-analysis; thrombosis, including ischemic cerebral events (transient or not) and venous thrombosis (DVD) /pulmonary embolism (PE) and bleeding, including major bleeding and clinically relevant non-major bleeding. RESULTS: In the NOACs treated group, thrombosis occurred less frequently in obese vs non-obese patients; RR and 95 % CI 0,75 (0,58-0,97), p = 0,03, while low heterogeneity was observed (I2= 40 %). In the warfarin treated subgroup there was statistically significant difference with less thrombotic events occurring in the obese vs non-obese patients; RR and (95 % CI) 0,80 (0,66-0,98), p = 0,03, and heterogeneity was low (I2 = 24 %). This protective effect called the obesity paradox is limited to obese patients anticoagulated for non-valvular atrial fibrillation (NVAF); RR (95 % CI) was 0,70 (0,58-0,85) p = 0,03 and I2 = 24 %. Bleeding events were similar under both NOACs and warfarin in obese vs non-obese analysis. CONCLUSIONS: Obese patients anticoagulated for NVAF with either standard dose of xabans or INR guided warfarin are more efficiently protected against thrombosis compared to non-obese patients.

Bleeding Risk in Patients Receiving Omega-3 Polyunsaturated Fatty Acids: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: There is a potential concern about increased bleeding risk in patients receiving omega-3 polyunsaturated fatty acids (PUFAs). The aims of this study-level meta-analysis were to determine the risk of bleeding and to assess whether this relationship is linked to the received dose of omega-3 PUFAs or the background use of antiplatelet treatment. METHODS AND RESULTS: Electronic databases were searched through May 2023 to identify randomized clinical trials of patients receiving omega-3 PUFAs. Overall bleeding events, including fatal and central nervous system events, were identified and compared with those of a control group. A total of 120 643 patients from 11 randomized clinical trials were included. There was no difference in the pooled meta-analytic events of bleeding among patients receiving omega-3 PUFAs and those in the control group (rate ratio [RR], 1.09 [95% CI, 0.91-1.31]; P=0.34). Likewise, the incidence of hemorrhagic stroke, intracranial bleeding, and gastrointestinal bleeding were similar. A prespecified analysis was performed in patients receiving high-dose purified eicosapentaenoic acid (EPA), which demonstrated a 50% increase in the relative risk of bleeding but only a modest increase in the absolute risk of bleeding (0.6%) when compared with placebo. Bleeding risk was associated with the dose of EPA (risk difference, 0.24 [95% CI, 0.05-0.43]; P=0.02) but not the background use of antiplatelet therapy (risk difference, -0.01 [95% CI, -0.02 to 0]; P=0.056). CONCLUSIONS: Omega-3 PUFAs were not associated with increased bleeding risk. Patients receiving high-dose purified EPA may incur additional bleeding risk, although its clinical significance is very modest.