Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants for Japanese Patients With Venous Thromboembolism　- The Primary Results From the KUROSIO Study.

BACKGROUND: Direct oral anticoagulants (DOACs) are recommended as the first-choice anticoagulation therapy in the acute phase of venous thromboembolism (VTE). However, there is limited real-world data for Japanese VTE patients.Methods and Results: The KUROSIO study (UMIN000023747) was a prospective long-term observational study comprising 1,017 patients with concurrent acute symptomatic pulmonary thromboembolism and proximal deep vein thrombosis (DVT) or isolated calf DVT initially treated with DOACs. After excluding 24 patients, 993 (mean age, 66.3±15.1 years; 58.6% females) were analyzed. The incidences of recurrent symptomatic VTE and major bleeding for up to 52 weeks after diagnosis were 3.2% and 2.2%, respectively. Multivariate analyses revealed chemotherapy and anemia as significant risk factors associated with recurrent symptomatic VTE and major bleeding, respectively. CONCLUSIONS: The efficacy and safety of DOACs in Japanese patients with VTE were determined in this real-world observational study.

Revascularization and Digestive Tract Repair in Secondary Aortoenteric Fistula Using a Single-Center in Situ Revascularization Strategy.

BACKGROUND: Information regarding optimal revascularization and digestive tract repair in secondary aortoenteric fistula (sAEF) remains unclear. Thus, reporting treatment outcomes and presenting comprehensive patient details through a structured treatment approach are necessary to establish a treatment strategy for this rare, complex, and fatal condition. METHODS: We performed a single-center retrospective review of consecutive sAEF managed based on our in situ revascularization and intestinal repair strategy. The primary endpoint of this study was all-cause mortality, and secondary endpoints were the incidence of in-hospital complications and midterm reinfections. RESULTS: Between 2007 and 2020, 16 patients with sAEF, including 13 men (81%), underwent in situ revascularization and digestive tract repair. The median follow-up duration for all participants was 36 (interquartile range, 6-62) months. Among the participants, 81% (n = 13), 13% (n = 2), and 6% (n = 1) underwent aortic reconstruction with rifampin-soaked grafts, unsoaked Dacron grafts, and femoral veins, respectively. The duodenum was the most commonly involved site in enteric pathology (88%; n = 14), and 57% (n = 8) of duodenal breaks were repaired by a simple closure. Duodenum's second part-jejunum anastomosis was performed in 43% of patients (n = 6), and 19% of the patients (n = 3) died perioperatively. In-hospital complications occurred in 88% patients (n = 14), and the most frequent complication was gastrointestinal. Finally, 81% patients (n = 13) were discharged home. Oral antibiotics were administered for a median duration of 5.7 months postoperatively; subsequently, the participants were followed up carefully. Reinfection was detected in 6% of the patients (n = 1) who underwent reoperation without any complications. The 1-year and 3-year overall survival rates of participants were 75% (n = 12) and 75% (n = 9), respectively, and no sAEF-related deaths occurred, except perioperative death. CONCLUSIONS: Surgical intervention with contemporary management based on our vascular strategy and digestive tract procedure may be a durable treatment for sAEF.

Serious Adverse Events with Cyanoacrylate Closure of Varicose Veins: An Initial Report from a Large-Scale National Survey in Japan.

Objective: Cyanoacrylate closure (CAC) is a minimally invasive technique for the treatment of varicose veins. A recent paper reported serious adverse events (AEs) associated with this use. This triggered an urgent survey to determine the incidence of AEs in Japan. Methods: The CAC-AE survey was sent to all 1,030 institutions authorized for CAC treatments. Cases performed between January 2020 and October 2023 were surveyed. Data on serious AEs and mortality were collected. Results: There were 623 surveys returned. There were 16 cases of proximal deep vein thrombosis, 3 cases of pulmonary embolism (PE), and 0 cases of stroke. Deep vein occlusion due to cyanoacrylate extension was observed in 1 case. Vein resection due to infection was observed in 4 cases. There were 299 cases of localized phlebitis and/or allergic reactions requiring steroid administration. Systemic allergic reactions requiring steroid administration were observed in 66 cases. There was no anaphylaxis associated with cyanoacrylate. There was one postoperative death from PE. Conclusion: This report's intent is to provide real world data on serious AEs following CAC from Japan given current concern over these events. An extensive report investigation of individual complications with analysis including causality will be provided following a full investigation separately.

The impact of renal function on clinical outcomes of patients with cancer-associated isolated distal deep vein thrombosis: Insights from the ONCO DVT study.

BACKGROUND: The multicenter, open-label, randomized clinical trial ONCO DVT compared 3-month and 12-month edoxaban treatment regimens for isolated distal deep vein thrombosis (DVT) and suggested potential benefits of prolonged edoxaban treatment in terms of thrombotic risk. However, the risk-benefit balance of prolonged edoxaban treatment in patients with renal function remains unclear. OBJECTIVES: To compare the safety and efficacy of 3-month and 12-month edoxaban treatment regimens in patients with cancer-associated isolated distal DVT and different renal functions. METHODS: This pre-specified subgroup analysis of the ONCO DVT study included 601 patients divided into subgroups according to renal function using a 50 mL/min creatinine clearance (Ccr) cutoff. The primary endpoint was symptomatic recurrent venous thromboembolism (VTE) and VTE-related death at 12 months and the major secondary endpoint was major bleeding at 12 months. RESULTS: Among the 601 patients, 131 (21.8 %) comprised the renal dysfunction subgroup. The primary endpoint occurred in 6 (9.7 %) and 1 (1.4 %) patients in the 3-month and 12-month edoxaban groups in the renal dysfunction subgroup, respectively, and in 16 (6.6 %) and 2 (0.9 %) patients in the no renal dysfunction subgroup, respectively. The major secondary endpoint occurred in 9 (14.5 %) and 7 (10.1 %) patients in the 12-month and 3-month edoxaban groups in the renal dysfunction subgroup, and in 13 (5.3 %) and 21 (9.3 %) patients in the no renal dysfunction subgroup, respectively. CONCLUSIONS: A 12-month edoxaban regiment was superior to a 3-month treatment in terms of thrombotic risk irrespective of renal function. A higher bleeding risk was not identified in patients with renal dysfunction who received prolonged edoxaban treatment.

Prophylactic Anticoagulation and Thrombosis in Hospitalized Patients with Clinically Stable COVID-19 at Admission: From the Practice-Based Observational Study.

Objectives: The potential benefit of routine prophylactic anticoagulation for all hospitalized patients with clinically stable coronavirus disease 2019 (COVID-19) is still controversial. Method: The CLOT-COVID Study was a multicenter observational study enrolling 2894 consecutive hospitalized patients with COVID-19. The current study population consisted of 1738 hospitalized patients with mild COVID-19 at admission not requiring oxygen administration, who were divided into 2 groups: patients with prophylactic anticoagulation (n = 326) and those without (n = 1412). Results: Patients with prophylactic anticoagulation had more severe status of the worst severity of COVID-19 during hospitalization compared with those without (mild: 38% versus 82%, moderate: 55% versus 17%, and severe or death at discharge: 6.4% versus 0.7%, P <0.001). During hospitalization, 8 patients (0.5%) developed thrombosis, and the incidences of thrombosis were numerically higher in patients with more severe status of worst severity of COVID-19 during hospitalization (mild: 0.2%, moderate: 1.2%, and severe or death at discharge: 3.2%). Conclusions: Among hospitalized patients with clinically stable COVID-19 at admission, patients who did not worsen in COVID-19 severity after admission rarely developed thrombosis, although patients with worsening of COVID-19 severity after admission more often received prophylactic anticoagulation and might have a higher risk of thrombosis.

Edoxaban for 12 vs. 3 months in cancer-associated isolated distal deep vein thrombosis according to different doses: insights from the ONCO DVT study.

BACKGROUND: The ONCO DVT study revealed the superiority of 12-month relative to 3-month edoxaban treatment for cancer-associated isolated distal deep vein thrombosis (DVT) regarding the thrombotic risk. METHODS AND RESULTS: In this pre-specified subgroup analysis of the ONCO DVT study, we stratified the patients into those with a standard edoxaban dose (60 mg/day; N = 151) and those with a reduced edoxaban dose (30 mg/day; N = 450) and evaluated the clinical outcomes for the 12- and 3-month treatments. The cumulative 12-month incidence of symptomatic recurrent venous thromboembolism was lower in the 12-month than 3-month group for both the 60 mg (1.3% vs. 11.6%, P = 0.02; odds ratio [OR], 0.12; 95% confidence interval [CI], 0.01-0.97) and 30 mg (1.1% vs. 7.6%, P = 0.002; OR, 0.14; 95% CI, 0.03-0.60) edoxaban subgroups, which was consistent across the edoxaban doses without a significant interaction (P = 0.90). The 12-month cumulative incidence of major bleeding was higher in the 12-month group than in the 3-month group for the 60 mg edoxaban subgroup (14.3% vs. 4.4%, P = 0.046; OR, 3.61; 95% CI, 0.97-13.52), whereas it did not significantly differ between the two groups for the 30 mg edoxaban subgroup (8.7% vs. 8.6%, P = 0.89; OR, 0.97; 95% CI, 0.49-1.91), signalling there was a potential interaction (P = 0.07). CONCLUSIONS: A 12-month edoxaban regimen for cancer-associated isolated distal DVT was consistently superior to a 3-month regimen, across the edoxaban doses for the thrombotic risk. However, caution was suggested for the standard dose of edoxaban due to the potential for an increased risk of bleeding with prolonged anticoagulation therapy. TRIAL REGISTRATION NUMBER: NCT03895502 (ONCO DVT Trial): https://classic.clinicaltrials.gov/ct2/show/NCT03895502.