Clinical Comprehensive Evaluation of Oral Anticoagulants Based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition) / 医药导报

Objective A comprehensive evaluation of oral anticoagulants(OACs)was conducted using the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),to provide a reference for drug selection and clinical medication decisions in medical institutions.Methods Evaluation evidence was collected,and the drugs included in the evaluation were quantified on four dimensions of clinical properties(efficiency and safety),pharmaceutical properties,economy and others.Results All oral anticoagulants included in the evaluation had a score of 70 or higher in the comprehensive evaluation,while warfarin had the highest overall score.Clinical properties and pharmacologic properties were identified as the core attributes for drug selection evaluation.When considering only these factors,edoxaban received the highest score.Conclusion OACs are the preferred option for patients requiring long-term anticoagulation therapy.Various OACs offer distinct clinical advantages.Utilizing the Guidelines(Second Edition)for oral anticoagulant selection and evaluation can offer visual evidence for drug selection and promote the scientific,rational,and safe use of drugs in clinical management.

Advances in direct oral anticoagulants in the treatment of cirrhosis-associated portal vein thrombosis / 临床肝胆病杂志

Portal vein thrombosis is one of the common complications of liver cirrhosis, and anticoagulation is currently the main treatment method for this disease. Since low-molecular-weight heparin must be injected and vitamin K antagonists require regular monitoring of international normalized ratio (INR), direct oral anticoagulants have become a research hotspot in replacement therapy with the advantages of convenient oral administration, no need for INR monitoring, and high recanalization rate. This article summarizes the advances in direct oral anticoagulants in the treatment of cirrhosis-associated portal vein thrombosis, in order to lay a foundation for further clinical studies.

Efficacy and Safety of Rivaroxaban and Dabigatran in Anticoagulant Therapy for Patients with Non-valvular Atrial Fibrillation combined with Diabetes Mellitus / 医药导报

Objective To investigate the efficacy and safety of new oral anticoagulants(NOACs)rivaroxaban and dabigatran versus warfarin in the treatment of the patients with non-valvular atrial fibrillation combined with diabetes mellitus.Methods A retrospective study was performed on 119 cases of patients with non-valvular atrial fibrillation combined with diabetes mellitus from outpatient and inpatient of the Ninth People's Hospital of Suzhou City from Jan 2019 to June 2021.According to the use of anticoagulants,patients were divided into rivaroxaban 10 mg group(Group A,n=25),rivaroxaban 15 mg group(Group B,n=30),dabigatran group(Group C,n=29),and warfarin group(Group D,n=35).All patients were treated continuously for at least 6 months.The incidence of embolism and bleeding events,the changes of coagulation indicator,blood glucose,liver and kidney function indexes were compared before and after treatment among the four groups.Results Thromboembolic events:1 cases(4.00%)of stoke or thromboembolic events occurred in Group A;2 cases(6.67%)occurred in Group B;2 cases(6.90%)occurred in Group C,and 5 cases(14.28%)occurred in Group D.Bleeding events:1 cases(4.00%)of bleeding events occurred in Group A;1 cases(3.33%)occurred in Group B;2 cases(6.90%)occurred in Group C,and 8 cases(22.85%)occurred in Group D.There was no statistically significant difference among the four groups of stoke or thromboembolic events(P>0.05).The incidence of bleeding events in Group A and B were both statistically lower than Group D(P<0.05),and the risk of bleeding events of Group C was similar to Group D(P>0.05)and there was also no statistically significant difference among Group A,B and C(P>0.05).The activated partial thromboplastin time(APTT)of all patients was significantly prolonged after treatment compared with before treatment(P<0.05),but none of them exceeded the upper limit of the normal value by 2 times.The APTT and international normalized ratio(INR)values of Group A and B,INR values of Group C were all statistically better than those of Group D(P<0.05)after the treatment.There were no statistically significant difference in the comparison of blood glucose,liver and kidney function index as well(P>0.05).Conclusion The new oral anticoagulants rivaroxaban and dabigatran showed similar effects in prevention of stroke or thromboembolic events,but better safety profiles with lower risks of bleeding events compared to warfarin in patients with non-valvular atrial fibrillation combined with diabetes mellitus.Dabigatran is comparable in efficacy and safety when compared with rivaroxaban and deserves to be promoted for clinical use.

Timing of rivaroxaban re-administration after upper gastrointestinal bleeding in patients with lower extremity deep venous thrombosis / 中国基层医药

Objective:To investigate the timing of rivaroxaban re-administration after upper gastrointestinal bleeding in patients with lower extremity deep venous thrombosis.Methods:The clinical data of 176 patients who suffered from lower limb deep vein thrombosis due to trauma or surgery and upper gastrointestinal bleeding due to oral rivaroxaban and received treatment in the Third Hospital of Hebei Medical University from May 2018 to October 2021 were retrospectively analyzed. These patients were divided into an early group (≤ 7 days) ( n = 84 cases) and a late group (> 7 days) ( n = 92 cases) according to the timing of rivaroxaban re-administration. All patients were followed up for 2 months to record hemoglobin, D-dimer, and platelet values. The progression of deep venous thrombosis of the lower extremities was observed. The rebleeding rate, progression of lower extremity deep venous thrombosis, and mortality were analyzed. Results:There were no significant differences in hemoglobin and D-dimer levels between the two groups on admission (both P > 0.05). After admission, the D-dimer level in the late group was (4.1 ± 2.3) mg/L, which was significantly higher than (3.1 ± 1.9) mg/L in the early group ( t = 3.17, P < 0.05). After admission, hemoglobin level in each group was significantly decreased compared with that on admission (both P < 0.05). The lowest hemoglobin level in the late group was (78.7 ± 8.3) g/L, which was significantly higher than (75.6 ± 8.2) g/L in the early group ( t = 2.32, P < 0.05). There was no significant difference in rebleeding rate between early and late groups [5.95% (5/84) vs. 1.08% (1/92)] (log-rank 3.07, P > 0.05). Lower extremity deep venous thrombosis progressed more slowly in the early group compared with the late group [2.38% (2/84) vs. 10.86% (10/92)] (log-rank = 4.61, P < 0.05). Conclusion:Rivaroxaban should be re-administered as soon as possible after upper gastrointestinal bleeding in patients with lower extremity deep venous thrombosis.

Effect of tranexamic acid combined with rivaroxaban on perioperative blood loss in patients undergoing posterior lumbar interbody fusion and its benefits / 中国基层医药

Objective:To investigate the effect of tranexamic acid combined with rivaroxaban on perioperative blood loss in patients undergoing posterior lumbar interbody fusion and its potential benefits.Methods:This is a retrospective study. The clinical data of 90 patients who underwent posterior lumbar interbody fusion for lumbar spinal stenosis or spondylolisthesis at Affiliated Hospital of Jining Medical University between September 2019 and September 2021 were analyzed. These patients were divided into two groups: group A ( n = 46) and group B ( n = 44) based on their medication. Patients in group A received an intravenous infusion of 0.5 g tranexamic acid and 100 mL of 5% glucose injection 15 minutes before the surgical incision. The incision wound was soaked externally with 1 g of tranexamic acid solution for 5 minutes before the surgical incision was closed, and it was suctioned before its closure. Patients in group B received the same procedure, except that oral rivaroxaban was administered 10 mg, once daily, after surgery till 35 days after surgery. The operative time, intraoperative blood loss, and the amount of drainage were recorded. Total blood loss, occult blood loss, incidence of lower extremity deep vein thrombosis, incidence of pulmonary embolism and epidural hematoma, and C-reactive protein levels were determined. Results:There were no significant differences in operative time, intraoperative blood loss, the amount of drainage, total blood loss, and occult blood loss between the two groups (all P > 0.05). Postoperative C-reactive protein levels in group A [29.94 (15.75, 50.25) mg/L] were significantly higher than those in group B [7.89 (4.94, 11.10) mg/L, Z = -5.68; P < 0.05]. Lower extremity deep vein thrombosis, pulmonary embolism, or epidural hematoma did not occur in either group. In group A, one patient was infused with 200 mL of leucodepleted red blood cell suspension, while the other patient received 150 mL of autologous blood transfusion. In group B, two patients were infused with 525 mL and 200 mL of leucodepleted red blood cell suspensions, respectively, while the rest did not require blood transfusion. Conclusion:The combined use of tranexamic acid and rivaroxaban after posterior lumbar interbody fusion does not increase perioperative bleeding, and it has additional anti-inflammatory effects without increasing the incidence of lower extremity deep vein thrombosis and pulmonary embolism, as well as the formation of epidural hematomas and the need for blood transfusion.

Pharmacoeconomic evaluation of different doses of rivaroxaban for the prevention of thrombosis in patients with nonvalvular atrial fibrillation / 中国药师

Objective To compare the cost and effectiveness of the new oral anticoagulant rivaroxaban 15 mg or 20 mg once a day for the prevention of thrombosis in patients with nonvalvular atrial fibrillation,and to provide references for clinical rational use of drugs.Method The Markov model was used to simulate the survival status of the two dose groups within 30 years,and the cost and health output were calculated separately to obtain the incremental cost-utility ratio(ICUR).Take 3 times of per capita gross domestic product(GDP)in China in 2020 as the willingness-to-pay threshold(WTP)to judge its economy.Results During the simulation period,compared with the 15 mg dose group,the 20 mg dose group had cumulative utility improvement of 0.97 quality-adjusted life-year(QALY),had an ICUR of 119 855 Yuan/QALY,had higher GDP and lower WTP,and was economical.Single-factor sensitivity analysis showed that the price and discount rate of the two doses of drugs were the main factors affecting ICUR.The probability sensitivity analysis pointed out that when the WTP was 3 times the per capita GDP,the 20 mg dose was more acceptable(65.2％),and the standard dose of 20 mg had a greater cost-utility advantage.Conclusion For patients with nonvalvular atrial fibrillation who take rivaroxaban for a long time to prevent thrombosis,choosing the instructional dose of 20 mg once a day is more cost-effective advantageous than the smaller dose of 15 mg once a day.

Compliance with oral rivaroxaban and its influencing factors in patients with lower extremity deep vein thrombosis:a clinical analysis / 介入放射学杂志

Objective To investigate the current status of the compliance with oral rivaroxaban in patients with lower extremity deep vein thrombosis(LEDVT),and to analyze the factors influencing patient medication compliance.Methods Using convenience sampling method,a total of 144 LEDVT patients,who needed to take anticoagulant therapy for a long time after discharged from the Affiliated Hospital of Nantong University of China,were selected as the research objects.The general information questionnaire,Morisky Medication Adherence Scale(MMAS),Beliefs about Medication Questionnaire(BMQ),Hospital Anxiety and Depression Scale(HADS)and Multidimensional Fatigue Inventor(MFI)were used to conduct the cross-sectional survey.Multiple linear regression was used to analyze the factors influencing medication compliance in patients with LEDVT.Results The median score of medication compliance in 144 LEDVT patients was 7(4.13,8)points.Multiple linear regression analysis showed that medication belief(P=0.014),depression(P=0.042),fatigue(P=0.008),type of coexisting chronic diseases(P=0.001),and number of types of medication(P=0.001)were the main factors influencing medication compliance.Conclusion The compliance with oral rivaroxaban in LEDVT patients is at a moderate level.Nursing staff should pay attention to patient's compliance with oral rivaroxaban,formulate effective intervention measures for the main influencing factors,relieve fatigue and depression degree of patients,so as to improve patient's medication belief and medication compliance,and to improve the quality of life.(J Intervent Radiol,2023,32:1246-1250)

Efficacy and safety of percutaneous left atrial appendage occlusion for nonvalvular atrial fibrillation / 中国基层医药

Objective:To investigate the efficacy and safety of percutaneous left atrial appendage occlusion in the treatment of nonvalvular atrial fibrillation.Methods:Eighty-eight patients with percutaneous left nonvalvular atrial fibrillation who received treatment in The Second Hospital of Anhui Medical University from January 2019 to January 2021 were included in this study. These patients were divided into three groups according to different anticoagulant methods: group A (percutaneous left atrial appendage occlusion), group B (livaraban), and group C (warfarin). The incidence of stroke, the incidence of bleeding events, the incidence of adverse cardiovascular events, and live and kidney function and coagulation function after 3 months of treatment were compared among the three groups.Results:There were no significant differences in the incidence of stroke and adverse cardiovascular events among the three groups ( P > 0.05). The incidence of bleeding events in groups A, B, and C was 9.3% (3/32), 15.0% (6/40), and 31.2% (5/16), respectively. There was a significant difference in the incidence of bleeding events among the three groups ( χ2 = 8.07, P = 0.001). After 3 months of treatment, there were no significant differences in prothrombin time, fibrinogen, prothrombin time-international normalized ratio, alanine aminotransferase, aspartate transaminase, and creatinine clearance among the three groups (all P > 0.05). Conclusion:Percutaneous left atrial appendage occlusion, warfarin, and rivaroxaban can prevent stroke in patients with nonvalvular atrial fibrillation. Percutaneous left atrial appendage occlusion is safer and more feasible than warfarin and rivaroxaban alone in the treatment of nonvalvular atrial fibrillation.

Efficacy and safety of rivaroxaban in different doses for the treatment of isolated distal deep vein thrombosis / 中华普通外科杂志

Objective:To evaluate the efficacy and safety of of rivaroxaban for different doses in the treatment of isolated distal deep vein thrombosis.Methods:The clinical data of 853 patients of isolated distal deep vein thrombosis attending Nanjing Drum Tower Hospital from Jan 2018 to Dec 2020 was retrospectively analyzed.Results:Thrombotic recurrence rate increased with increasing follow-up in the standard and low dose groups, and it was significantly lower in the standard dose group than in the low dose group (HR=0.44, 95% CI: 0.25-0.78, P=0.005) with most thrombosis occurring within the first year of follow-up. There was no statistical difference between the two groups in terms of major bleeding events (HR=1.70,95%CI 0.56-5.14, P=0.530) and the incidence of clinically relevant non-major bleeding events was significantly higher in the standard dose group than in the low dose group (HR=2.36, 95%CI 1.26-4.44, P=0.020). Subgroup analysis on anticoagulation duration found when anticoagulation duration was longer than 1.5 months, the risk of thrombosis was lower in the standard dose group than the low dose group (1.5-3 months:HR=0.11, 95%CI 0.01-0.87, >3 months: HR=0.19, 95%CI 0.04-0.95), there was an interaction between anticoagulation duration and dose ( P=0.007). Conclusions:Based on the risk of thrombosis recurrence and bleeding events, the standard dose of rivaroxaban (20 mg qd) is recommended for patients with isolated distal deep vein thrombosis, and the anticoagulant duration should be maintained for 1.5 months or more.

Rivaxaban combined with antiplatelet drugs in ischemic stroke patients with atrial fibrillation and intracranial artery stenosis: comparison with rivaroxaban alone / 国际脑血管病杂志

Objective:To investigate the efficacy and safety of rivaroxaban combined with antiplatelet in ischemic stroke patients with non-valvular atrial fibrillation and moderate or severe intracranial artery stenosis.Methods:The consecutive ischemic stroke patients with non-valvular atrial fibrillation and moderate or severe intracranial artery stenosis admitted to Yantai Yuhuangding Hospital of Qingdao University from August 2019 to March 2022 were retrospectively included. According to the secondary prevention drugs, the patients were divided into rivaroxaban and rivaroxaban combined with antiplatelet treatment group. The basic characteristics of the two groups were compared. The primary outcome was the recurrence rate of stroke at 3 months, and the secondary outcome included the incidence of any bleeding event at 3 months, the all-cause mortality rate, the improvement rate of neurological function, and the good outcome rate. The good outcome was defined as the modified Rankin Scale ≤2 points at 3 months.Results:A total of 108 patients aged 70.72±8.08 years old were included in the study. There were 56 patients (51.9%) in the rivaroxaban group and 52 (48.1%) in the combined treatment group. In terms of primary outcome, the recurrence rate of stroke in the combined treatment group was significantly lower than that in the rivaroxaban group at 3 months (7.69% vs. 21.43%; P<0.05). In terms of secondary outcomes, the incidence of bleeding events in the combined treatment group at 3 months was significantly higher than that in the rivaroxaban group (26.92% vs. 7.14%; P<0.05), with one death event in each group. The rate of good outcome in the combined treatment group was significantly higher than that in the rivaroxaban group (75.00% vs. 51.79%; P=0.013). Multivariate logistic regression analysis showed that high National Institutes of Health Stroke Scale (NIHSS) score at admission was an independent risk factor for poor outcome (odds ratio 1.370, 95% confidence interval 1.057-1.776; P=0.018), while the rivaroxaban combined antiplatelet treatment was an independent protective factor for stroke recurrence (odds ratio 0.203, 95% confidence interval 0.054-0.758; P=0.018). Conclusion:After ischemic stroke in patients with non-valvular atrial fibrillation complicated with moderate and severe stenosis of intracranial artery, rivaroxaban combined with antiplatelet treatment can reduce the recurrence rate of stroke and improve the clinical outcome, but it may increase the risk of bleeding.

Prognostic value of AST/ALT ratio combined with APTT regimen in NVAF patients receiving rivaroxaban anticoagulant therapy / 国际生物医学工程杂志

Objective:To investigate the prognostic value of the ratio of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) combined with activated partial thromboplastin time (APTT) in elderly patients with non-valvular atrial fibrillation (NVAF) treated with rivaroxaban.Methods:One hundred and twenty-two elderly patients with NVAF who were anticoagulated with rivaroxaban from June 2020 to June 2021 in the Third Central Hospital of Tianjin were enrolled and divided into four groups based on the median method. The patients in the Q1 group ( n = 32) have low AST/ALT/low APTT. The patients in the Q2 group ( n = 27) have low AST/ALT/high APTT. The patients in the Q3 group ( n = 29) have high AST/ALT/low APTT. The patients in the Q4 group ( n = 34) have high AST/ALT/high APTT. The efficacy endpoint events, and safety endpoint events were analyzed in the four groups, and univariate and multivariate Cox regression analyses were performed for the composite endpoint events. Results:The effectiveness endpoint events were mainly cardiovascular deaths, the number of which in the Q1 to Q4 groups was 0 (0), 1 (3.70%), 4 (13.79%), and 5 (14.71%), respectively. The safety endpoint events were mainly non-major bleeding events, the number of which in the Q1 to Q4 groups was 5 (15.62%), 2 (7.41%), 6 (20.69%), and 5 (14.71%), respectively. Compared to the Q1 group, the Q4 group had an increased risk of composite endpoint events after incorporating traditional risk factor correction ( HR: 3.851, 95% CI: 1.167 to 12.704). Conclusions:AST/ALT ratio combined with APTT can provide risk stratification for distant bleeding and cardiovascular adverse events in elderly NVAF patients treated with rivaroxaban anticoagulation and has some predictive value for their prognosis.

Research progress in plasma concentration monitoring of rivaroxaban / 中国临床药理学与治疗学

Rivaroxaban, a novel oral anticoagulant drug, is widely prescribed in clinical practice. Rivaroxaban offers predictable pharmacokinetic and pharmacodynamic properties, a lowprobability of drug-drug and food-drug interactions. Compared with warfarin, rivaroxaban does not require continuous therapeutic monitoring and can be administered in fixed doses.However,in certain emergency clinical situations, such as bleeding, acute stroke, acute kidney injury, prior to urgent surgery and in the suspected accumulation of durg, plasma concentration monitoring of rivaroxaban is necessary and important for patients. Existing studies proved that there were significant individual variability and wide range in the plasma rivaroxaban concentration, which increased the risk of clinical use. Therefore, Data in the degree of rivaroxaban concentration may provide recommendations for the clinical application to promote medication safety and individuality in the future. This article collected the latest literatures and case reports related to research progress of rivaroxaban plasma concentration monitoring, and Summarized influencing factors, monitoring methods, so as to provide a basis for further study on rational use of rivaroxaban in clinical.

Research advances in rivaroxaban in the treatment of portal vein thrombosis in liver cirrhosis / 临床肝胆病杂志

Portal vein thrombosis (PVT) is one of the common complications of liver cirrhosis and is associated with the poor prognosis of liver disease. Rivaroxaban, a novel direct oral anticoagulant, exerts an antithrombotic effect by directly acting on the active center of factor Xa to inhibit the generation of thrombin, and it is a new choice for long-term anticoagulant treatment of PVT in liver cirrhosis with the advantages of direct oral administration and no need for international normalized ratio (INR) monitoring. In recent years, more and more clinical studies have shown that rivaroxaban is relatively safe and effective in the treatment of PVT in liver cirrhosis; however, there is still little experience in the application of rivaroxaban in the treatment of PVT in liver cirrhosis in the current clinical practice, and individualized medication regimen remains to be clarified. This article reviews the research advances in rivaroxaban in the treatment of PVT in liver cirrhosis, in order to provide new ideas for the clinical treatment of PVT in liver cirrhosis.

Rivaroxabana em Pacientes Ambulatoriais com COVID-19 Leve ou Moderada: Fundamentação e Desenho do Estudo CARE (CARE - Coalition COVID-19 Brazil VIII) / Rivaroxaban in Outpatients with Mild or Moderate COVID-19: Rationale and Design of the Study CARE (CARE - Coalition COVID-19 Brazil VIII)

Resumo Fundamento Estudos anteriores revelaram alto risco de eventos tromboembólicos arteriais e venosos como consequência de danos virais diretos do SARS-CoV-2 em células endoteliais e um meio procoagulante devido ao aumento de biomarcadores como o D-dímero, fibrinogênio, fator VIII. Foram realizados ensaios controlados randomizados de terapias antitrombóticas em pacientes internados, no entanto, poucos estudos avaliaram o papel da tromboprofilaxia no ambiente ambulatorial. Objetivo Avaliar se a profilaxia antitrombótica com rivaroxabana reduz o risco de eventos trombóticos venosos ou arteriais, suporte ventilatório invasivo e morte em pacientes ambulatoriais com COVID-19. Métodos O estudo CARE é um ensaio randomizado, aberto, multicêntrico e controlado por rivaroxabana 10 mg uma vez por dia durante 14 dias ou tratamento local padrão isolado, para a prevenção de resultados adversos, registrado no Clinicaltrials.gov (NCT04757857). Os critérios de inclusão são adultos com infecção confirmada ou suspeita do SARS-CoV-2, com sintomas leves ou moderados, sem indicação de hospitalização, no prazo de 7 dias após o início dos sintomas e um fator de risco de complicação da COVID-19 (>65 anos, hipertensão, diabetes, asma, doença pulmonar obstrutiva crônica ou outras doenças pulmonares crônicas, tabagismo, imunossupressão ou obesidade). O desfecho primário composto inclui tromboembolismo venoso, necessidade de ventilação mecânica invasiva, eventos cardiovasculares agudos maiores e mortalidade no prazo de 30 dias após a randomização, sendo avaliado segundo o princípio da intenção de tratar. Todos os pacientes assinaram termo de consentimento. Foi estabelecido um nível de significância de 5% para todos os testes estatísticos. Resultados Os principais desfechos trombóticos e hemorrágicos, hospitalizações e mortes serão avaliados centralmente por um comitê de eventos clínicos independente, sob a condição cega para a alocação dos grupos de tratamento. Conclusão O estudo CARE fornecerá informação relevante e contemporânea sobre o possível papel da tromboprofilaxia em pacientes ambulatoriais com COVID-19.

Abstract Background Previous studies have demonstrated a high risk of arterial and venous thromboembolic events as a consequence of direct viral damage to endothelial cells by SARS-CoV-2 and a procoagulant milieu due to increased biomarkers, such as D-dimer, fibrinogen, and factor VIII. Although randomized controlled trials of antithrombotic therapies have been conducted in hospitalized patients, few have evaluated the role of thromboprophylaxis in an outpatient setting. Objective To assess whether antithrombotic prophylaxis with rivaroxaban reduces the risk of venous or arterial thrombotic events, invasive ventilatory support, and death in COVID-19 outpatients. Methods The COVID Antithrombotic Rivaroxaban Evaluation (CARE) study, a multicenter, randomized, open-label, controlled trial of rivaroxaban 10 mg once daily for 14 days or local standard treatment alone to prevent adverse outcomes, is registered in clinicaltrials.gov (NCT04757857). The inclusion criteria are adults with confirmed or suspected SARS-CoV-2 infection and mild or moderate symptoms without indication for hospitalization, within 7 days of symptom onset, and 1 risk factor for COVID-19 complication (> 65 years, hypertension, diabetes mellitus, asthma, chronic obstructive pulmonary disease or other chronic lung diseases, smoking, immunosuppression, or obesity). The primary composite endpoint, which includes venous thromboembolism, invasive mechanical ventilation, major acute cardiovascular events, and mortality within 30 days of randomization, will be assessed according to the intention-to-treat principle. All patients will provide informed consent. A significance level of 5% will be used for all statistical tests. Results Major thrombotic and bleeding outcomes, hospitalizations, and deaths will be centrally adjudicated by an independent clinical events committee blinded to the assigned treatment groups. Conclusion The CARE study will provide relevant and contemporary information about the potential role of thromboprophylaxis in outpatients with COVID-19.

Successful use of rivaroxaban achieving therapeutic anti-factor xa levels in a morbidly obese patient with acute intermediate-high risk pulmonary embolism / Uso bem-sucedido de rivaroxabana com níveis terapêuticos de antifator xa em paciente com obesidade mórbida e embolia pulmonar aguda de risco intermediário-alto

Abstract Direct oral anticoagulants (DOACs) have become the standard of care for acute and long-term therapy for venous thromboembolism (VTE) due to their efficacy and safety profiles. The 2021 International Society on Thrombosis and Haemostasis guidelines recommend using standard DOAC dosages in patients with BMI >40 kg/m2 or weight >120 kg. Use of DOACs remains uncertain in morbidly obese patients with VTE, including acute PE. A morbidly obese woman in her 30s who presented with acute worsening of dyspnea was diagnosed with acute intermediate-high risk acute pulmonary embolism and concomitant proximal deep vein thrombosis, constituting a clinically challenging scenario for treating her with rivaroxaban. Standard doses of rivaroxaban for acute and extended phase treatment of venous thromboembolism in individuals with morbid obesity at BMI>70 kg/m2 may be effective, and safe.

Resumo Devido à sua eficácia e aos seus perfis de segurança, os anticoagulantes orais diretos (DOACs) tornaram-se o padrão de cuidado para a terapia aguda e de longo prazo de tromboembolismo venoso (TEV). As diretrizes da Sociedade Internacional de Trombose e Hemostasia de 2021 recomendam o uso de dosagens padrão de DOACs em pacientes com índice de massa corporal (IMC) > 40 kg/m2 ou peso > 120 kg. O uso de DOACs em pacientes com obesidade mórbida e TEV, incluindo embolia pulmonar aguda, ainda não foi esclarecido. Uma mulher com obesidade mórbida na faixa dos 30 anos que apresentou piora aguda da dispneia foi diagnosticada com embolia pulmonar aguda de risco intermediário-alto e trombose venosa profunda proximal concomitante, com o cenário clínico desafiador de tratá-la com rivaroxabana. Doses padrão de rivaroxabana para tratamento e recorrência de tromboembolismo venoso em indivíduos com obesidade mórbida e IMC > 70 kg/m2 podem ser eficazes e seguras.

Evaluation, preparation, and description of chitosan nanoparticles, as well as improving rivaroxaban bioavailability

The aim of the present study is the Evaluation, preparation, and description of chitosan nanoparticles and bioavilibility enhancement of rivaroxaban. Preparation of Rivaroxaban nanoparticles (RB-NPs) were prepared by the ionic gelation method. Different parameters were studied for evaluation, Preparation & description of nanoparticles. The results of the present study showed that the formulation F7 showed the significant results for all the selected parameter as compared to the other formulations. The formulation F1, F5, and F6 showed the highest production yield (52.5, 52.35, and 52.35% respectively) and F7 showed the significant production yield (51.85%), zeta-potential (23.63 mV), entrapment efficiency (99.87), particle size (316.12±2.14 nm) and poly disparity index (0.32). Nanoparticles are solid colloidal drug carriers ranging from 10—1000 nm in diameter and are composed of synthetic, natural or semi-synthetic polymers encapsulating the drug molecule.

Aspirin versus Rivaroxaban to Prevent Venous Thromboembolism after Total Knee Arthroplasty: A Double-blinded, Randomized Controlled Trial / Aspirina versus rivaroxabana na prevenção do tromboembolismo venoso após artroplastia total do joelho: Um ensaio clínico randomizado, controlado e duplo-cego

Abstract Objective Aspirin (acetylsalicylic acid, ASA) and rivaroxaban are anticoagulants that have increased in popularity due to ease of use in the prevention of venous thromboembolism (VTE) after total knee arthroplasty (TKA). The present study aimed to evaluate the efficacy of ASA compared with that of rivaroxaban on VTE prophylaxis in patients who underwent TKA. Method Forty patients who had primary knee osteoarthritis and would undergo TKA were randomized into two groups. In total, 20 patients in the ASA group used oral aspirin, at a dose of 300 mg/day, for VTE prophylaxis after TKA, while 20 patients in the rivaroxaban group received oral rivaroxaban, at a dose of 10 mg/day. On days 4 and 14 after the operation, deep vein thrombosis (DVT) in the lower limbs on the operated side was detected through duplex ultrasonography. Other complications were recorded for 14 days. Results There were no positive findings of DVT detected with duplex ultrasonography in the groups of patients, and the occurrence of pulmonary embolism was not observed. In total, 4 patients had subcutaneous ecchymosis on the fourth postoperative day (2 patients in the ASA group and 2 patients in the rivaroxaban group; p= 1.0), and another 4 patients on the fourteenth postoperative day (1 patient in the ASA group and 3 patients in the rivaroxaban group; p= 0.292). No cases of wound hematoma, major organ bleeding, wound infection, or reoperation were observed in the sample. Conclusion Aspirin and rivaroxaban had comparable efficacy to prevent VTE, without increasing the incidence of wound complications and bleeding after TKA.

Resumo Objetivo A aspirina (ácido acetilsalicílico, AAS) e a rivaroxabana são anticoagulantes que vêm ganhando popularidade devido à facilidade de uso na prevenção do tromboembolismo venoso (TEV) após artroplastia total do joelho (ATJ). Este estudo teve como objetivo avaliar a eficácia do AAS em comparação com a da rivaroxabana na profilaxia de TEV em pacientes submetidos a ATJ. Método Quarenta pacientes com osteoartrite primária do joelho, que seriam submetidos a ATJ, foram randomizados em dois grupos. No total, 20 pacientes do grupo AAS usaram aspirina oral, na dose de 300 mg/dia, para a profilaxia do TEV após ATJ; e 20 pacientes do grupo rivaroxabana receberam uma dose oral de 10 mg/dia. No 4° e 14° dias do pós-operatório, trombose venosa profunda (TVP) dos membros inferiores no lado da cirurgia foi detectada por meio de ultrassonografia duplex. Foram registradas outras complicações durante catorze dias. Resultados Não foram detectados achados positivos de TVP com a ultrassonografia duplex nos grupos de pacientes, e não se observou a ocorrência de embolia pulmonar. No total, 4 pacientes apresentaram equimose subcutânea no 4° dia do pós-operatório (2 pacientes no grupo AAS e 2 pacientes no grupo rivaroxabana; p= 1,0), e outros 4 pacientes, no 14° dia do pós-operatório (1 paciente no grupo AAS e 3 pacientes no grupo rivaroxabana; p= 0,292). Nenhum paciente da amostra apresentou hematoma da ferida cirúrgica, sangramento de órgão importante, infecção da ferida, ou necessidade de nova cirurgia. Conclusão A aspirina e a rivaroxabana apresentaram eficácia comparável na prevenção do TEV, sem aumentar a incidência de complicações da ferida e sangramento após ATJ.

Safety and preventive effects of rivaroxaban and low-molecular-weight heparin on deep vein thrombosis of lower extremity after total hip arthroplasty

Deep vein thrombosis (DVT) is a common complication of skeletal surgery, which can cause disability and death in severe cases. Here, we have compared the preventive effects of rivaroxaban and low molecular weight heparin on DVT of lower extremity after total hip arthroplasty and the safety. A total of 310 patients who received total hip arthroplasty from May 2014 to June 2016 were divided into a rivaroxaban group (n=153) and a low molecular weight heparin group (n=157). The rivaroxaban group was orally administered with rivaroxaban (10 mg, qd) 12 h after surgery for 30 consecutive days, and the other group was subcutaneously injected with low molecular weight heparin calcium injection (0.6 mL, ad) for 7 consecutive days. The incidence rate of lower extremity DVT, drainage blood volume, hemoglobin decline, as well as preoperative and postoperative 7-d prothrombin time (PT), activated partial thromboplastin time (APTT), platelet (PLT) count and D-dimer level of the two groups were compared. The two groups had similar incidence rates of lower extremity DVT, drainage blood volumes and extents of hemoglobin decline (P >0.05). There were no significant differences in the preoperative and postoperative 7-d PT, APTT, PLT counts and D-dimer levels between the two groups (P >0.05). Rivaroxaban and low molecular weight heparin show comparable preventive effects on lower extremity DVT after total hip arthroplasty. Results suggest that rivaroxaban is superior than the low molecular weight heparin in terms of convenient use (oral administration), good compliance and absence of dose adjustment.

Avaliação da bioequivalência entre duas formulações de rivaroxabana ­ 20 mg comprimido revestido ­ administradas em jejum e pós-prandial em voluntários sadios / Evaluation of bioequivalence between two rivaroxaban formulations ­ coated tablet 20 mg ­ administered under fasting and fed conditions in healthy volunteers

Objetivo: O objetivo deste trabalho foi avaliar a bioequivalência entre duas formulações de rivaroxabana 20 mg comprimido revestido, sendo a formulação teste produzida por Sanofi Medley, Brasil e a formulação referência (Xarelto®) comercializada por Bayer S/A. Métodos: Os estudos foram conduzidos em voluntários sadios de ambos os sexos e as formulações foram administradas em dose única, sob o estado de jejum e pós-prandial. Cada estudo foi conduzido de maneira independente, sendo ambos do tipo aberto, randomizado e com intervalo (washout) de sete dias entre os períodos. O estudo em jejum foi realizado em quatro períodos, com 48 voluntários, enquanto o pós-prandial foi realizado em dois períodos, com 36 voluntários. Resultados: Na administração em jejum, a razão entre a média geométrica da formulação teste e referência (T/R) de Cmáx foi de 100,77%, com intervalo de confiança de 90% (IC 90%) de 94,24% a 107,76%. Para ASC0-t, a razão T/R foi de 100,65%, com IC 90% de 96,13% a 105,39%. Na administração pós-prandial, a razão T/R de Cmáx foi de 110,63%, com IC 90% de 102,39% a 119,54%. Para ASC0-t, a razão T/R foi de 104,65%, com IC 90% de 98,44% a 109,12%. Conclusões: As formulações teste e referência foram consideradas estatisticamente bioequivalentes em ambas as condições de administração, de acordo com os critérios exigidos pela Agência Nacional de Vigilância Sanitária (Anvisa). A formulação teste foi registrada na Anvisa e disponibilizada para comercialização, contribuindo, assim, para a ampliação da disponibilidade do tratamento para doenças tromboembólicas e para a redução de custos ao paciente e ao Sistema Único de Saúde.

Objective: The objective of the present study was to evaluate the bioequivalence between two formulations of rivaroxaban 20 mg coated tablet, the test formulation being manufactured by Sanofi Medley, Brazil and the reference formulation (Xarelto® ) commercialized by Bayer S/A. Methods: The studies were conducted in healthy volunteers of both sexes and the formulations were administered in a single dose, under fasting and fed conditions. Each study was conducted independently, both being open-label, randomized and with a seven-day interval (washout) between periods. The fasting study was carried out in four periods, with 48 volunteers, while the fed study was carried out in two periods, with 36 volunteers. Results: In the fasting administration, the ratio between.

Recomendaciones de manejo de los anticoagulantes orales directos (DOACs) anti Xa y anti IIa / Recommendations for the practical management of the direct oral anticoagulants anti Xa and anti IIa

Resumen Los anticoagulantes orales directos han surgido como una de las herramientas que ha cambiado el manejo de la enfermedad trombótica en los últimos 15 años. Sus ventajas, desde el punto de vista de la facilidad de uso y menor riesgo de sangrado, especialmente de sangrado cerebral, han posicionado a estos nuevos anticoagulantes como la primera alternativa de tratamiento en las dos indicaciones más frecuentes en que necesitamos estas drogas, la fibrilación auricular y la enfermedad tromboembólica venosa. Sin embargo, no todos los pacientes pueden recibir estos agentes, no todos los anticoagulantes directos tienen las mismas pro piedades y fundamentalmente, no todas las enfermedades con indicación de un anticoagulante pueden tratarse con ellos;con lo cual es necesario que todos los profesionales que están involucrados en el manejo de estos medicamentos estén obligados a conocerlos en profundidad, para poder decidir el mejor tratamiento en cada caso particular. Este documento de posición de expertos de diferentes especialidades de Argentina, presenta lineamientos para el uso correcto de los anticoagulantes directos en base a nueva evidencia y a la experiencia de uso de un amplio grupo de profesionales. La forma de relacionarnos con el tratamiento anticoagulante ha cambiado. Los médicos que trabajamos con ellos también debemos hacerlo.

Abstract Direct oral anticoagulants have emerged as the drugs that have changed the man agement of the antithrombotic treatment in the last 15 years. Their advantages, like a more friendly way of anticoagulation and their lower risk of bleeding, especially in the brain, have positioned these new anticoagu lants as the first drug of choice in the two most frequent indications of anticoagulation, atrial fibrillation, and the venous thromboembolic disease. However, not all the patients can receive these agents, not all the direct oral anticoagulants have the same characteristics, and most importantly, not all the diseases with an indication of an anticoagulant drug can be treated with them. Therefore, it is mandatory that all the faculties involved in the management of these drugs must know them in depth, to decide the best treatment for the patient. This position paper, from a group of experts in anticoagulation in Argentina, can help the general practitioner in the daily use of direct oral anticoagulants based on the new evidence and the experience of a wide group of professionals. The way we relate to the anticoagulant treatment has changed in the last years. The doctors who work with them must also do so.