Rivaroxaban Versus Enoxaparin for Thromboprophylaxis After major Gynecological Cancer Surgery: The VALERIA Trial : Venous thromboembolism prophylAxis after gynecoLogical pElvic cancer surgery with RIvaroxaban versus enoxAparin (VALERIA trial).

Direct oral anticoagulants (DOACs) for venous thromboembolism (VTE) prevention after major gynecological cancer surgery might be an alternative to parenteral low-molecular-weight heparin (LMWH). Patients undergoing major gynecological cancer surgery were randomized at hospital discharge to receive rivaroxaban 10 mg once daily or enoxaparin 40 mg once daily for 30 days. The primary efficacy outcome was a combination of symptomatic VTE and VTE-related death or asymptomatic VTE at day 30. The primary safety outcome was the incidence of major or clinically relevant nonmajor bleeding. Two hundred and twenty-eight patients were enrolled and randomly assigned to receive rivaroxaban (n = 114)or enoxaparin (n = 114). The trial was stopped due to a lower-than-expected event rate. The primary efficacy outcome occurred in 3.51% of patients assigned to rivaroxaban and in 4.39% of patients assigned to enoxaparin (relative risk 0.80, 95% CI 0.22 to 2.90; p = 0.7344). Patients assigned to rivaroxaban had no primary bleeding event, and 3 patients (2.63%) in the enoxaparin group had a major or CRNM bleeding event (hazard ratio, 0.14; 95% CI, 0.007 to 2.73; P = 0.1963). In patients undergoing major gynecological cancer surgery, thromboprophylaxis with rivaroxaban 10 mg daily for 30 days had similar rates of thrombotic and bleeding events compared to parenteral enoxaparin 40 mg daily. While the power is limited due to not reaching the intended sample size, our results support the hypothesis that DOACs might be an attractive alternative strategy to LMWH to prevent VTE in this high-risk population.

Rivaroxaban with Aspirin Versus Aspirin for Peripheral Arterial Disease and Intermittent Claudication. Rationale and Design of the COMPASS CLAUDICATION Trial.

BACKGROUND: The COMPASS trial demonstrated that in patients with peripheral arterial disease, the combination of rivaroxaban and aspirin compared with aspirin reduces the risk of major adverse limb events, but it is not known whether this combination can also improve symptoms in patients with intermittent claudication. The primary objective of this study is to evaluate the effect of the combination on claudication distance. STUDY DESIGN: Eighty-eight patients with intermittent claudication will be randomized to receive rivaroxaban 2.5 mg twice daily plus aspirin 100 mg once daily or aspirin 100 mg once daily for 24 weeks. The primary outcome is the change in claudication distance from the baseline to 24 weeks, measured by 6 min walking test and treadmill test. The primary safety outcome is the incidence of major bleeding and clinically relevant non-major bleeding according to the International Society on Thrombosis and Hemostasis criteria. SUMMARY: The COMPASS CLAUDICATION trial will provide high-quality evidence regarding the effect of the combination of rivaroxaban and aspirin on claudication distance in patients with peripheral arterial disease.

Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial.

BACKGROUND: Patients hospitalised with COVID-19 are at risk for thrombotic events after discharge; the role of extended thromboprophylaxis in this population is unknown. METHODS: In this open-label, multicentre, randomised trial conducted at 14 centres in Brazil, patients hospitalised with COVID-19 at increased risk for venous thromboembolism (International Medical Prevention Registry on Venous Thromboembolism [IMPROVE] venous thromboembolism [VTE] score of ≥4 or 2-3 with a D-dimer >500 ng/mL) were randomly assigned (1:1) to receive, at hospital discharge, rivaroxaban 10 mg/day or no anticoagulation for 35 days. The primary efficacy outcome in an intention-to-treat analysis was a composite of symptomatic or fatal venous thromboembolism, asymptomatic venous thromboembolism on bilateral lower-limb venous ultrasound and CT pulmonary angiogram, symptomatic arterial thromboembolism, and cardiovascular death at day 35. Adjudication was blinded. The primary safety outcome was major bleeding. The primary and safety analyses were carried out in the intention-to-treat population. This trial is registered at ClinicalTrials.gov, NCT04662684. FINDINGS: From Oct 8, 2020, to June 29, 2021, 997 patients were screened. Of these patients, 677 did not meet eligibility criteria; the remaining 320 patients were enrolled and randomly assigned to receive rivaroxaban (n=160 [50%]) or no anticoagulation (n=160 [50%]). All patients received thromboprophylaxis with standard doses of heparin during hospitalisation. 165 (52%) patients were in the intensive care unit while hospitalised. 197 (62%) patients had an IMPROVE score of 2-3 and elevated D-dimer levels and 121 (38%) had a score of 4 or more. Two patients (one in each group) were lost to follow-up due to withdrawal of consent and not included in the intention-to-treat primary analysis. The primary efficacy outcome occurred in five (3%) of 159 patients assigned to rivaroxaban and 15 (9%) of 159 patients assigned to no anticoagulation (relative risk 0·33, 95% CI 0·12-0·90; p=0·0293). No major bleeding occurred in either study group. Allergic reactions occurred in two (1%) patients in the rivaroxaban group. INTERPRETATION: In patients at high risk discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days improved clinical outcomes compared with no extended thromboprophylaxis. FUNDING: Bayer.

Medically Ill hospitalized Patients for COVID-19 THrombosis Extended ProphyLaxis with rivaroxaban ThErapy: Rationale and Design of the MICHELLE Trial.

BACKGROUND: The devastating Coronavirus disease (COVID-19) pandemic is associated with a high prothrombotic state. It is unclear if the coagulation abnormalities occur because of the direct effect of SARS-CoV-2 or indirectly by the cytokine storm and endothelial damage or by a combination of mechanisms. There is a clear indication of in-hospital pharmacological thromboprophylaxis for every patient with COVID-19 after bleed risk assessment. However, there is much debate regarding the best dosage regimen, and there is no consensus on the role of extended thromboprophylaxis. DESIGN: This study aims to evaluate the safety and efficacy of rivaroxaban 10 mg once daily for 35 ± 4 days versus no intervention after hospital discharge in COVID-19 patients who were at increased risk for VTE and have received standard parenteral VTE prophylaxis during hospitalization. The composite efficacy endpoint is a combination of symptomatic VTE, VTE-related death, VTE detected by bilateral lower limbs venous duplex scan and computed tomography pulmonary angiogram on day 35 ± 4 posthospital discharge and symptomatic arterial thromboembolism (myocardial infarction, nonhemorrhagic stroke, major adverse limb events, and cardiovascular death) up to day 35 ± 4 posthospital discharge. The key safety outcome is the incidence of major bleeding according to ISTH criteria. SUMMARY: The MICHELLE trial is expected to provide high-quality evidence around the role of extended thromboprophylaxis in COVID-19 and will help guide medical decisions in clinical practice.1.

Efficacy and Safety of a Biosimilar Versus Branded Enoxaparin in the Prevention of Venous Thromboembolism Following Major Abdominal Surgery: A Randomized, Prospective, Single-Blinded, Multicenter Clinical Trial.

Several biosimilar versions of enoxaparin are already approved and in use globally. Analytical characterization can establish good quality control in manufacturing, but they may not assure similarity in clinical outcomes between biosimilar and branded enoxaparin. This study evaluated the efficacy and safety of biosimilar Cristália versus branded Sanofi enoxaparin in venous thromboembolism (VTE) prevention in patients undergoing major abdominal surgery at risk for VTE. In this randomized, prospective single-blind study, we compared Cristália enoxaparin (Ce), a biosimilar version, versus branded Sanofi enoxaparin (Se; at a dose of 40 mg subcutaneously per day postoperatively from 7 to 10 days) in 243 patients submitted to major abdominal surgery at risk for VTE for VTE prevention. The primary efficacy outcome was occurrence of VTE or death related to VTE. The principal safety outcomes were a combination of major bleeding and clinically relevant non-major bleeding. Bilateral duplex scanning of the legs was performed from days 10 to 14, and follow-ups were performed up to 60 days after surgery. The incidence of VTE was 4.9% in the Cristália group and 1.1% in the Sanofi group (absolute risk difference = 3.80%, 95% confidence interval [CI]: -1.4%-9.0%) yielding noninferiority since the 95% CI does not reach the prespecified value Δ = 20%. Clinically significant bleeding occurred in 9.9% in the Cristália group and in 5.5% in the Sanofi group (n.s. ). In conclusion, this study suggests that 40 mg once daily of Ce, a biosimilar enoxaparin, is as effective and safe as the branded Sanofi enoxaparin in the prophylaxis of VTE in patients submitted to major abdominal surgery at risk for VTE.

Carotid stenosis: what is the high-risk population?

OBJECTIVE: Prevention is the best treatment for cerebrovascular disease, which is why early diagnosis and the immediate treatment of carotid stenosis contribute significantly to reducing the incidence of stroke. Given its silent nature, 80% of stroke cases occur in asymptomatic individuals, emphasizing the importance of screening individuals with carotid stenosis and identifying high-risk groups for the disease. The aim of this study was to determine the prevalence and the most frequent risk factors for carotid stenosis. METHODS: A transversal study was conducted in the form of a stroke prevention campaign held on three nonconsecutive Saturdays. During the sessions, carotid stenosis diagnostic procedures were performed for 500 individuals aged 60 years or older who had systemic arterial hypertension and/or diabetes mellitus and/or coronary heart disease and/or a family history of stroke. RESULTS: The prevalence of carotid stenosis in the population studied was 7.4%, and the most frequent risk factors identified were mean age of 70 years, carotid bruit, peripheral obstructive arterial disease, coronary insufficiency and smoking. Independent predictive factors of carotid stenosis include the presence of carotid bruit or peripheral obstructive arterial disease [corrected] and/or coronary insufficiency. CONCLUSIONS: The population with peripheral obstructive arterial disease [corrected] and/or coronary insufficiency and carotid bruit should undergo routine screening for carotid stenosis.

Carotid stenosis: what is the high-risk population?

OBJECTIVE: Prevention is the best treatment for cerebrovascular disease, which is why early diagnosis and the immediate treatment of carotid stenosis contribute significantly to reducing the incidence of stroke. Given its silent nature, 80% of stroke cases occur in asymptomatic individuals, emphasizing the importance of screening individuals with carotid stenosis and identifying high-risk groups for the disease. The aim of this study was to determine the prevalence and the most frequent risk factors for carotid stenosis. METHODS: A transversal study was conducted in the form of a stroke prevention campaign held on three nonconsecutive Saturdays. During the sessions, carotid stenosis diagnostic procedures were performed for 500 individuals aged 60 years or older who had systemic arterial hypertension and/or diabetes mellitus and/or coronary heart disease and/or a family history of stroke. RESULTS: The prevalence of carotid stenosis in the population studied was 7.4%, and the most frequent risk factors identified were mean age of 70 years, carotid bruit, peripheral obstructive arterial disease, coronary insufficiency and smoking. Independent predictive factors of carotid stenosis include the presence of carotid bruit or peripheral obstructive heart disease and/or coronary insufficiency. CONCLUSIONS: The population with peripheral obstructive heart disease and carotid bruit should undergo routine screening for carotid stenosis.

Avaliação da maturação das fístulas arteriovenosas para hemodiálise pelo eco-Doppler colorido / Evaluation of hemodialysis arteriovenous fistula maturation by color-flow Doppler ultrasound

CONTEXTO: Quando se confecciona uma fístula arteriovenosa para hemodiálise (FAVH) autógena, é necessário que se aguarde a dilatação da veia em questão e o desenvolvimento de volume de fluxo mínimo, fenômeno chamado de maturação. Ainda hoje se discute qual o tempo necessário para ocorrer essa maturação. OBJETIVO: Avaliar a maturação de FAVH utilizando-se critérios ecográficos. MÉTODO: Entre maio de 2004 e 2005, 40 pacientes foram selecionados prospectivamente, sendo 23 homens (57,5%), com média de idade de 17,5±51,3 anos, com indicação de confecção de uma FAVH. Utilizou-se o aparelho Logic III® com transdutor de 10 MHz para a avaliação no pré-operatório e nos 7º, 14º, 21º e 28º dias de pós-operatório. Os critérios para a maturação após a cirurgia foram: veia com diâmetro médio maior que 4 mm e volume de fluxo maior que 400 mL/min. RESULTADOS: O diâmetro médio pré-operatório foi de 3,24±1,43 e 3,71±1,37 mm para fístulas de punho e de cotovelo, respectivamente. O diâmetro final foi de 5,01±0,87 mm para as FAVH de punho (p = 0,006) e de 6,15±1,16 mm para as FAVH de cotovelo (p = 0,95). O volume de fluxo no 7º dia pós-operatório foi de 493,63±257,49 mL/min e 976,33±332,90 mL/min para as FAVH de punho e cotovelo, respectivamente. Ao final do estudo, foi calculado o valor de 556,81±288,42 mL/min nas FAVH de punho (p < 0,05) e de 1031,62±614,812 mL/min nas FAVH de cotovelo. Baseados nos dois critérios, a maturação ocorreu em 57,1% das fístulas de punho e em 100% das fístulas de cotovelo após a 1ª semana. Após 4 semanas, 67,9% das fístulas de punho e 100 por cento das fístulas de cotovelo apresentaram maturação. CONCLUSÃO: A maioria das FAVH de cotovelo apresentou diâmetro e fluxo adequados para punção logo após a 1ª semana de pós-operatório. Para as FAVH de punho, houve melhora progressiva dos padrões de maturação com o passar das semanas, sugerindo que essas FAVH devem ser puncionadas preferencialmente após...

BACKGROUND: When a hemodialysis arteriovenous fistula (HAVF) is created, it is important to wait for venous dilatation and volume flow increase through the HAVF, a phenomenon called maturation. There is still some controversy as to the exact time required for this maturation to occur. OBJECTIVE: To evaluate the time required for HAVF maturation using ultrasound criteria. METHOD: From May 2004 through May 2005, 40 patients were prospectively selected. The sample was comprised of 23 men (57.5%), mean age of 51.3±17.5 years, with indication of HAVF creation. Logic III® ultrasound with 10 MHz transducer probe was used for pre- and postoperative evaluation 7, 14, 21 and 28 days after the procedure. Criteria for maturation after the procedure were vein diameter larger than 4 mm and volume flow larger than 400 mL/min. RESULTS: Preoperative mean diameter was 3.24±1.43 and 3.71±1.37 mm for fist and elbow fistula, respectively. Final diameter of the fist HAVF was 5.01±0.87 mm (p = 0.006) and 6.15±1.16 mm for the elbow HAVF (p = 0.95). Flow volume in the 7th postoperative day was 493.63±257.49 and 976.33±332.90 mL/min, respectively, for the fist and elbow HAVF. At the end of the study, the value of 556.81±288.42 mL/min was calculated for the fist HAVF (p < 0.05) and 1,031.62±614.812 mL/min for the elbow HAVF. Based on both cut-off values, maturation occurred in 57.1% of the fist fistula and in 100% of the elbow fistula after the first week. After 4 weeks, 67.9% of the fist HAVF and 100% of the elbow HAVF presented maturation. CONCLUSION: Most elbow HAVF showed adequate diameter and flow volume for puncture 1 week after the procedure. For the fist fistula, gradual maturation occurred throughout the weeks, suggesting that these HAVF should be punctured 4 weeks after the surgery.