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.

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.

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.

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.

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.

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.

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.

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.

Bilateral adrenal hemorrhage caused by anticoagulant therapy after joint replacement surgery: One case report and literature review / 中华内分泌代谢杂志

Bilateral adrenal hemorrhage is a rare cause of primary adrenal insufficiency, and bilateral adrenal hemorrhage due to anticoagulant use is even rarer. We describe the case of a 62-year-old woman receiving post total knee arthroplasty anticoagulant therapy who presented fever, vomitting, stomachache, and severe fatigue on the 8th day. It was until 4 months later that the patient was finally diagnosed with adrenal insufficiency resuting from bilateral adrenal hemorrhage, her symptoms were relieved by glucocorticoid replacement therapy. In order to promote the awareness, diagnosis, and mangement of post-surgery anticoagulants induced bilateral adrenal hemorrhage, the clinical characteristics of the reported cases were summarized and analyzed.

Effect of rivaroxaban combined with ateplase on acute pulmonary embolism and its influence on inflammatory factors and coagulation function / 中国医师进修杂志

Objective:To investigate the therapeutic effect of rivaroxaban combined with ateplase on patients with acute pulmonary embolism and its influence on inflammatory factors and coagulation function.Methods:One hundred and two patients with acute pulmonary embolism admitted to the First People′s Hospital of Linping District from March 2016 to March 2020 were divided into observation group (51 cases) and control group (51 cases) by random number table.Methods:The control group was treated with ateplase, and the observation group was treated with rivaroxaban on the basis of the control group. The course of treatment in both groups was 10 d. The effective and the changes of arterial partial pressure of oxygen (PaO 2), partial pressure of carbon dioxide in artery (PaCO 2), heart rate(HR), inflammatory factors and coagulation index were compared before and after treatment between the two groups. Results:The total effective rate after treatment in the observation group was higher than that in the control group: 90.20%(46/51) vs. 68.63%(35/51), the difference was statistically significant ( χ2 = 7.256, P<0.05). The level of PaO 2 after treatment in the observation group was higher than that in the control group, the levels of PaCO 2 and HR after treatment in the observation group were lower than those in the control group: (82.91 ± 4.35) mmHg (1 mmHg = 0.133 kPa) vs. (73.35 ± 2.97) mmHg, (34.21 ± 2.89) mmHg vs. (39.98 ± 3.25) mmHg, (76.83 ± 3.76) beats/min vs. (84.20 ± 3.15) beats/min, the differences were statistically significant ( t = 12.96, 9.48, 9.17, P<0.05). The levels of interleukin (IL)- 1β, IL-6 and tumor necrosis factor-α after treatment in the observation group were lower than those in the control group: (0.62 ± 0.20) μg/L vs. (1.08 ± 0.23) μg/L, (15.42 ± 2.53) μg/L vs.(20.93 ± 2.78) μg/L, (0.49 ± 0.16) μg/L vs. (0.78 ± 0.12) μg/L, the differences were statistically significant ( t = 10.78, 10.47, 10.36, P<0.05). The levels of fibrinogen, D-Dimer after treatment in the observation group were lower than those in the control group: (2.78 ± 0.61) g/L vs. (3.53 ± 0.54) g/L, (1.18 ± 0.23) mg/L vs. (1.69 ± 0.28) mg/L; but the levels of prothrombin time, activate part plasma prothrombin time after treatment in the observation group were longer than those in the control group: (15.85 ± 1.48) s vs. (13.04 ± 1.27) s, (40.79 ± 2.34) s vs. (37.46 ± 2.98)s, the differences were statistically significant ( t = 6.58, 10.05, 10.29, 6.28, P<0.05). Conclusions:Rivaroxaban combined with ateplase is effective in the treatment of acute pulmonary embolism, and it can reduce inflammatory reaction and improve coagulation function.

Advances in applied research of Rivaroxaban in children with thromboembolic disease / 中华实用儿科临床杂志

Rivaroxaban has been widely used for prevention and treatment of pulmonary embolism in adults due to the convenience of oral taking, rapid effect, less drug interaction, less influence by diet, no need of monitoring and fixed dose.However, its clinical application in children has been controversial.The EINSTEIN-Jr clinical trial and case reports at home and abroad have demonstrated the safety and effectiveness of Rivaroxaban in children with venous thrombus embolism.Therefore, Rivaroxaban can be considered as an alternative to standard anticoagulant therapy for children with venous thrombus embolism.This study reviews the application progress of Rivaroxaban in children with thromboembolic diseases.

Efecto de las diferentes drogas anticoagulantes sobre el ensayo de fibrinógeno derivado del tiempo de protrombina / Effect of different anticoagulant drugs on the prothrombin time-derived fibrinogen assay

Resumen El objetivo de este trabajo fue comparar los niveles de fibrinógeno (FBG) obtenidos por el método de Clauss con los obtenidos por el método de fibrinógeno derivado del tiempo de protrombina (FBG PT-d), con dos tromboplastinas, en pacientes anticoagulados con distintas drogas. Se estudiaron pacientes anticoagulados consecutivos: 105 con antagonistas de la vitamina K (AVK), 55 con heparina no fraccionada (HNF), 58 con heparina de bajo peso molecular (HBPM), 60 con rivaroxabán, 45 con apixabán, 60 con dabigatrán y 100 controles normales (CN). El FBG se determinó por el método de Clauss y FBG PT-d utilizando tromboplastina de cerebro de conejo o recombinante humana; los niveles de heparina, rivaroxabán y apixabán por método cromogénico anti Xa; el dabigatrán con el ensayo de tiempo de trombina diluido. Existió un sesgo positivo (p<0,001) al comparar el FBG PT-d vs. FBG por Clauss: CN: 13,7%, AVK: 31,8%, rivaroxabán: 34,8% y apixabán: 20,0% cuando se utilizó tromboplastina de conejo. En el caso de las muestras que contenían HBPM se observó este desvío con ambas tromboplastinas. El sesgo porcentual en presencia de dabigatrán y heparina no fraccionada no fue estadísticamente distinto del obtenido en el grupo control. El ensayo de FBG PT-d no debe utilizarse en pacientes anticoagulados con rivaroxabán, apixabán, HBPM o AVK, ya que sobreestima los niveles de FBG. El porcentaje de sesgo depende del tipo de tromboplastina utilizado y fue mayor con la de cerebro de conejo en el sistema de detección utilizado.

Abstract The aim of this study was to compare fibrinogen (FBG) results obtained by Clauss method (FBG-C) and by the prothrombin time-derived fibrinogen assay (FBG PT-d) with two thromboplastins in patients under anticoagulation. Consecutive anticoagulated patients were studied: 105 vitamin-K antagonist (VKA), 55 unfractioned heparin, 58 LMWH, 60 rivaroxaban, 45 apixaban and 60 dabigatran, and 100 healthy controls (NC). FBG-C was performed by Clauss and FIB PT-d with rabbit brain and human recombinant thromboplastins, respectively. Heparins, rivaroxaban and apixaban levels were measured by antiXa; dabigatran by thrombin diluted assay. A positive bias of FBG PT-d vs. FBG-C with both thromboplastins were seen in NC (13.7 and 19.0 % for HS and RP, respectively), but bias with HS in rivaroxaban, apixaban and VKA patients were significantly higher compared to NC: 34.8%, 20.0 % and 31.8 %, respectively. LMWH presented higher BIAS compared to NC with both thromboplastins. Samples with unfraction heparin and dabigatran presented similar bias to NC. FBG PT-d should not be used in patients under anticoagulant treatment because of an important overestimation of FBG could be obtained in these patients. The percentage of bias depends on the type of thromboplastin used; it was higher with rabbit brain thromboplastin in the detection system used.

Resumo O objetivo deste trabalho foi comparar os níveis de fibrinogênio (FBG) obtidos pelo método de Clauss com aqueles obtidos pelo método do fibrinogênio derivado do tempo de protrombina (FBG PT-d), com duas tromboplastinas, em pacientes anticoagulados com diferentes drogas. Pacientes anticoagulados consecutivos foram estudados: 105 com antagonista da vitamina K (AVK); 55 com heparina não fracionada (UFH); 58 com heparina de baixo peso molecular (HBPM), 60 com rivaroxabana, 45 com apixabana, 60 com dabigatrana e 100 controles normais (CN). FBG foi determinado pelo método de Clauss e FBG PT-d usando tromboplastina de cérebro de coelho ou tromboplastina humana recombinante; níveis de heparina, rivaroxabana e apixabana pelo método cromogênico anti-Xa; dabigatrana com ensaio de tempo de trombina diluída. Há um viés positivo (p<0,001) ao comparar o FBG PT-d vs FBG de Clauss: CN: 13,7%; AVK: 31,8%, rivaroxabana: 34,8% e apixabana 20,0% quando foi utilizada tromboplastina de coelho. No caso das amostras contendo HBPM, esse desvio foi observado com ambas as tromboplastinas. O viés percentual na presença de dabigatrana e heparina não fracionada não foi estatisticamente diferente daquela obtida no grupo controle. O ensaio de FBG PT-d não deve ser usado em pacientes anticoagulados com rivaroxabana, apixabana, LMWH ou VKA, pois superestima os níveis de FBG. A porcentagem de viés depende do tipo de tromboplastina utilizado e foi maior com a de cérebro de coelho, no sistema de detecção utilizado.

Safety of oral anticoagulants in advanced chronic kidney disease / Seguridad de los anticoagulantes orales en enfermedad renal crónica avanzada

Abstract Background: patients who take long-term oral anticoagulants and also have CKD have a greater probability of bleeding. Methods: a retrospective, descriptive cohort study reviewing the clinical charts of anticoagulated patients with Stage 3 CKD or above seen at an anticoagulation clinic, in order to evaluate hemorrhagic events and baseline characteristics of the population over a two-year period. Results: 238 patients were included. The anticoagulants used were warfarin (45%), rivaroxaban (31.5%), apixaban (14.3%) and dabigatran (3.4%). According to the KDIGO classification, 78% of the patients had CKD G3 (37.3% G3a and 40.7% G3b), 15.9% G4 and 5.8% G5 with renal replace ment therapy (RRT). During the study period, only 20 patients (8.4%) had hemorrhagic events; of these, seven (35%) were major (four associated with warfarin, two with rivaroxaban and one with apixaban). The other 13 bleeds were minor and associated with warfarin in 46.1% of the cases. Gastrointestinal bleeding was the most common (35%), followed by soft tissues (30%). There was only one fatal bleed, which occurred in the central nervous system (CNS) in a patient with CKD G4. Conclusion: a low rate of bleeding was found, which could be related to close follow up by an anticoagulation clinic. The anticoagulant most frequently associated with bleeding was warfarin, which could be related to a low time in therapeutic range (48.8%). Due to the low rate of events, comparisons could not be made. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1945).

Resumen Antecedentes: los pacientes que toman anticoagulantes orales a largo plazo y además cursan con enfermedad renal crónica (ERC), tienen mayor probabilidad de tener sangrados. Métodos: estudio de cohorte descriptivo retrospectivo en el cual se revisaron historias clínicas de pacientes anticoagulados y con ERC 3 en adelante, atendidos en una clínica de anticoagulación con el fin de evaluar eventos hemorrágicos y características básales de la población en un periodo de dos años Resultados: se incluyeron 238 pacientes. Los anticoagulantes usados fueron warfarina (45%), rivaroxabán (31.5%), apixabán (14.3%) y dabigatrán (3.4%). Según la clasificación KDIGO 78% de los pacientes tenían ERC G3 (37.3% G3a y 40.7% G3b), 15.9% G4 y 5.8% G5 con terapia de reemplazo renal (TRR). En el periodo de estudio solo 20 pacientes (8.4%) tuvieron eventos hemo rrágicos, de estos, 7 (35%) fueron mayores (cuatro asociados a warfarina, dos rivaroxabán y uno apixabán). Los otros 13 sangrados fueron menores y asociados a warfarina en 46.1% de los casos. El sangrado digestivo fue el más frecuente (35%), seguido por tejidos blandos (30%). Sólo hubo un sangrado fatal el cual se dio en sistema nervioso central (SNC) en un paciente con ERC G4. Conclusión: se apreció una baja tasa de sangrado, lo que podría estar relacionado con el estrecho seguimiento de una clínica de anticoagulación. El anticoagulante que más frecuentemente se asoció con sangrado fue warfarina, lo cual puede estar relacionado con un bajo tiempo en rango terapéutico (48.8%). Por la baja tasa de eventos, no fue posible la realización de comparaciones. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1945).

Atrial Fibrillation and Use of Rivaroxaban: Performance of the Prothrombin Time / INR as a Function of Time After Blood Collection

Abstract Background Traditionally, the most effective therapy in the prevention of stroke in patients with atrial fibrillation (AF) has been oral anticoagulation with vitamin K inhibitors, particularly warfarin, whose disadvantages and adverse effects have led to their replacement by "direct oral anticoagulants", as factor X inhibitor. Objectives This study aimed to conduct a brief approach on atrial fibrillation (AF) and use of Rivaroxaban, and to comparatively evaluate the prothrombin time / International Normalized Ratio (PT/INR) in patients with AF in use of this oral anticoagulant, depending on the time elapsed between the last administration of the drug and the time of blood sample venipuncture. Methods We evaluated 34 patients with AF in use of Rivaroxaban by using PT / INR, distributed into a subgroup with blood collection time ≤ 12 hours (n = 7) and > 12 hours after the last drug intake (n = 27). Mann-Whitney test was used to compare the groups and p < 0.05 was considered significant. Results An analysis as a function of time between the Rivaroxaban intake and blood collection, revealed that PT / INR suffers the greatest effect up to 12 hours after ingestion of the drug, dropping to levels close to normal in subsequent hours before the next dose. Conclusion We concluded that, in contrast to warfarin, the knowledge of the time interval between drug intake and blood collection from patients taking Rivaroxaban is essential to properly interpret a laboratory test to assess hemostasis, particularly PT and its derivatives. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0