SEOM clinical guidelines on venous thromboembolism (VTE) and cancer (2023).

The Spanish Society of Medical Oncology (SEOM) last published clinical guidelines on venous thromboembolism (VTE) and cancer in 2019, with a partial update in 2020. In this new update to the guidelines, SEOM seeks to incorporate recent evidence, based on a critical review of the literature, to provide practical current recommendations for the prophylactic and therapeutic management of VTE in patients with cancer. Special clinical situations whose management and/or choice of currently recommended therapeutic options (low-molecular-weight heparins [LMWHs] or direct-acting oral anticoagulants [DOACs]) is controversial are included.

ABCG2 polymorphism and rivaroxaban pharmacokinetics in healthy individuals after a single dose

Rivaroxaban is a direct factor Xa inhibitor. Its interindividual variability is large and may be connected to the occurrence of adverse drug reactions or drug inefficacy. Pharmacogenetics studies concentrating on the reasons underlying rivaroxaban's inadequate response could help explain the differences in treatment results and medication safety profiles. Against this background, this study evaluated whether polymorphisms in the gene encoding the ABCG2 transporter modify the pharmacokinetic characteristics of rivaroxaban. A total of 117 healthy volunteers participated in two bioequivalence experiments with a single oral dose of 20 mg rivaroxaban, with one group fasting and the other being fed. Ultra-high-performance liquid chromatography coupled with mass spectrometry was employed to determine the plasma concentrations of rivaroxaban, and the WinNonlin program was used to calculate the pharmacokinetics parameters. In the fasting group, the rivaroxaban pharmacokinetic parameters of Vd (508.27 vs 334.45 vs 275.59 L) and t1/2 (41.04 vs 16.43 vs 15.47 h) were significantly higher in ABCG2 421 A/A genotype carriers than in ABCG2 421 C/C and 421 C/A genotype carriers (P<0.05). The mean values of Cmax (145.81 vs 176.27 vs 190.19 ng/mL), AUC0-t (1193.81 vs 1374.69 vs 1570.77 ng/mL·h), and Cl (11.82 vs 14.50 vs 13.01 mL/h) for these groups were lower, but this difference was not statistically significant (P>0.05). These findings suggested that the ABCG2 421 A/A genotype may impact rivaroxaban parameters after a single dose in healthy subjects. This finding must be validated before it is applied in clinical practice.

Central American and Caribbean Consensus Document for the Optimal Management of Oral Anticoagulation in Patients with Non-Valvular Atrial Fibrillation Endorsed by the Central American and Caribbean Society of Arterial Hypertension and Cardiovascular Prevention.

Atrial fibrillation (AF) is the most common arrhythmia in adults. Prevention of the ischaemic risk with oral anticoagulants (OACs) is widely recommended, and current clinical guidelines recommend direct oral anticoagulants (DOACs) as preference therapy for stroke prevention. However, there are currently no clinical practice guidelines or recommendation documents on the optimal management of OACs in patients with AF that specifically address and adapt to the Central American and Caribbean context. The aim of this Delphi-like study is to respond to doubts that may arise in the management of OACs in patients with non-valvular AF in this geographical area. A consensus project was performed on the basis of a systematic review of the literature, a recommended ADOLOPMENT-like approach, and the application of a two-round Delphi survey. In the first round, 31 recommendations were evaluated and 30 reached consensus, of which, 10 unanimously agreed. The study assessed expert opinions in a wide variety of contextualized recommendations for the optimal management of DOACs in patients with non-valvular atrial fibrillation (NVAF). There is a broad consensus on the clinical practice guideline (CPG) statements used related to anticoagulation indication, patient follow-up, anticoagulation therapy complications, COVID-19 management and prevention, and cardiac interventions.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and stage 5 chronic kidney disease under dialysis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: In patients with atrial fibrillation (AF) and normal or slightly impaired renal function, the use of direct oral anticoagulants (DOACs) is preferable to vitamin K antagonists (VKAs). However, in patients undergoing hemodialysis, the efficacy, and safety of DOACs compared with VKAs are still unknown. PURPOSE: To review current evidence about the safety and efficacy of DOACs compared to VKAs, in patients with AF and chronic kidney disease under hemodialysis. METHODS: We systematically searched PubMed, Scopus, and Cochrane databases for RCTs comparing DOACs with VKAs for anticoagulation in patients with AF on dialysis therapy. Outcomes of interest were: (1) stroke; (2) major bleeding; (3) cardiovascular mortality; and (4) all-cause mortality. Statistical analysis was performed using RevMan 5.1.7 and heterogeneity was assessed by I2 statistics. RESULTS: Three randomized controlled trials were included, comprising a total of 383 patients. Of these, 218 received DOACs (130 received apixaban; 88 received rivaroxaban), and 165 were treated with VKAs (116 received warfarin; 49 received phenprocoumon). The incidence of stroke was significantly lower in patients treated with DOACs (4.7%) compared with those using VKAs (9.5%) (RR 0.42; 95% CI 0.18-0.97; p = 0.04; I2 = 0%). However, the difference was not statistically significant in the case of ischemic stroke specifically (RR 0.42; 95% CI 0.17-1.04; p = 0.06; I2 = 0%). As for the major bleeding outcome, the DOAC group (11%) had fewer events than the VKA group (13.9%) but without statistical significance (RR 0.75; 95% CI 0.45-1.28; p = 0.29; I2 = 0%). There was no significant difference between groups regarding cardiovascular mortality (RR 1.23; 95% CI 0.66-2.29; p = 0.52; I2 = 13%) and all-cause mortality (RR 0.98; 95% CI 0.77-1.24; p = 0.84; I2 = 16%). CONCLUSION: This meta-analysis suggests that in patients with AF on dialysis, the use of DOACs was associated with a significant reduction in stroke, and a numerical trend of less incidence of major bleeding compared with VKAs, but in this case with no statistical significance. Results may be limited by a small sample size or insufficient statistical power.

Direct oral anticoagulants versus aspirin for primary thromboprophylaxis in patients with multiple myeloma undergoing outpatient therapy: A systematic review and updated meta-analysis.

Patients with multiple myeloma (MM) are at an elevated risk of venous thromboembolism (VTE), which is further increased for those undergoing anti-myeloma therapy. Current guidelines suggest low-dose direct oral anticoagulants (DOACs) as an alternative to aspirin for primary thromboprophylaxis in this population, but data comparing these two therapies are limited. We performed a systematic review and meta-analysis to compare DOACs with aspirin for primary thromboprophylaxis in individuals undergoing outpatient anti-myeloma therapy. Studies were selected when comparing DOACs versus aspirin for thrombotic and haemorrhagic outcomes. We included 10 randomised controlled trials and observational studies comprising 1026 patients with MM who received primary thromboprophylaxis with DOACs (n = 337) or aspirin (n = 689). DOAC thromboprophylaxis was associated with a significantly lower incidence of VTE compared with aspirin (OR 0.33; 95% CI 0.16-0.68; p < 0.001). Major, clinically relevant non-major and minor bleeding event rates did not differ significantly between groups. Overall, our meta-analysis suggests that DOACs may be a preferable option to aspirin for the prevention of MM-related thrombosis. However, these results should be interpreted in the context of heterogeneous baseline population characteristics and potential bias from including observational studies. Further research is needed to evaluate the optimal thromboprophylaxis strategy, particularly in high-risk individuals.

Successful use of rivaroxaban achieving therapeutic anti-factor xa levels in a morbidly obese patient with acute intermediate-high risk pulmonary embolism.

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.

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.

Cost-effectiveness analysis of extended thromboprophylaxis with rivaroxaban versus no prophylaxis in high-risk patients after hospitalisation for COVID-19: an economic modelling study.

Background: In patients at high risk of thromboembolism who were discharged after hospitalisation due to COVID-19, thromboprophylaxis with rivaroxaban 10 mg/day for 35 days significantly improved clinical outcomes, reducing thrombotic events compared with no post-discharge anticoagulation. The present study aimed to estimate the cost-effectiveness of this anticoagulation strategy. Methods: Using the database of the MICHELLE trial, we developed a decision tree to estimate the cost-effectiveness of thromboprophylaxis with rivaroxaban 10 mg/day for 35 days versus no thromboprophylaxis in high-risk post-discharge patients for COVID-19 through an incremental cost-effectiveness analysis. Findings: 318 patients in 14 centres in Brazil were enrolled in the primary MICHELLE trial. The mean age was 57.1 years (SD 15.2), 127 (40%) were women, 191 (60%) were men, and the mean body-mass index was 29.7 kg/m2 (SD 5.6). Rivaroxaban 10 mg per day orally for 35 days after discharge decreased the risk of events defined by the primary efficacy outcome by 67% (relative risk 0.33, 95% CI 0.12-0.90; p = 0.03). The mean cost for thromboprophylaxis with rivaroxaban was $53.37/patient, and no prophylaxis was $34.22/patient, with an incremental cost difference of $19.15. The effectiveness means obtained in the intervention group was 0.1457, while in the control group was 0.1421, determining an incremental QALY difference of 0.0036. The estimated incremental cost-effectiveness ratio (ICER) was $5385.52/QALY. Interpretation: Extended treatment with Rivaroxaban as thromboprophylaxis after hospital discharge for high-risk patients with COVID-19 is a cost-effective treatment option. Funding: Modest funding was provided by Science Valley Research Institute, São Paulo, Brazil.

An Update in Anticoagulant Therapy for Patients with Cancer-Associated Venous Thromboembolism.

PURPOSE OF REVIEW: This review aims to assess the treatment options for cancer-associated venous thromboembolism (VTE) based on the most robust level of evidence recommendations and suggestions based on expert opinion. RECENT FINDINGS: Several classes of anticoagulants have been studied in the treatment of cancer-associated thrombosis (CAT). Since the CLOT trial, guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of this condition. However, since 2018, some direct oral anticoagulants became an alternative first-line treatment for CAT. Three Xa antagonists (rivaroxaban, apixaban, and edoxaban) proved to be at least as effective as the LMWH strategy for the short-term prevention of VTE recurrence. The right choice of treatment in the context of anticoagulation strategy, thrombo-hemorrhagic risk management, and a patient's comorbidities represents a challenge. The correct management of CAT and a more individualized approach are needed to identify risk factors and offer the best treatment for each patient.

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.

Predictores de uso de anticoagulantes orales directos en tromboembolia pulmonar aguda / Predictors of use of direct oral anticoagulants in acute pulmonary embolism

Resumen Introducción: En la última década los anticoagulantes orales directos (ACOD) se incorporaron como herramienta para la anticoagulación en pacientes con tromboembolia pulmonar (TEP) aguda. Aunque tienen un mejor perfil farmacológico que los antagonistas de la vitamina K (AVK), el uso de estos fármacos no es masivo. El objetivo del presente trabajo fue evaluar el uso de ACOD en pacientes con TEP aguda y detectar determinantes de su indicación. Metodología: Análisis preespecificado del registro CONAREC XX que incorporó pacientes con TEP aguda en 64 centros de Argentina. Se realizó un análisis para detectar predictores de prescripción de ACOD al alta. Resultados: Se analizaron 579 pacientes que recibieron anticoagulación al alta hospitalaria: el 60% recibió AVK, el 21% heparinas y el 19% ACOD (de ellos, un 49% rivaroxabán, un 34% apixabán y un 17% dabigatrán). Los pacientes que recibieron ACOD tenían TEP de menor gravedad, menor riesgo de hemorragia y menos complicaciones intrahospitalarias. En el seguimiento a 30 días no hubo diferencias en mortalidad por todas las causas o sangrados. La cobertura de salud por un seguro social (odds ratio [OR] 7.45; intervalo de confianza del 95% [IC 95%]: 1.74-31.9; p < 0.01) o por cobertura privada (OR 10.5; IC 95%: 2.4-45.9; p < 0.01) fueron predictores independientes de la prescripción de ACOD al alta, y el antecedente de insuficiencia cardiaca (OR 0.19; IC 95%: 0.04-0.84; p = 0.028) y de enfermedad oncológica (OR 0.49; IC 95%: 0.27-0.89; p = 0.02) fueron predictores de no prescribirlos. Conclusiones: Uno de cada cinco supervivientes de TEP aguda recibió ACOD al egreso hospitalario en Argentina, y esto fue determinado por variables clínicas y económicas

Abstract Introduction: In the last decade, direct oral anticoagulants (DOACs) have been incorporated as an anticoagulation tool in patients with acute pulmonary thromboembolism (PTE). Although they have a better pharmacological profile than vitamin K antagonists (VKA), the use of these drugs is not massive. The objective of this study was to evaluate the use of DOACs in patients with acute PE and to detect determinants of its use. Methodology: Prespecified analysis of the CONAREC XX registry that included patients with acute PE in 64 centers in Argentina. An analysis was performed to detect predictors of DOAC prescription at discharge. Results: 579 patients who received anticoagulation at hospital discharge were analyzed: 60% received VKA, 21% heparin and 19% DOAC (of them, 49% Rivaroxaban, 34% Apixaban, and 17% Dabigatran). Patients receiving DOACs had less severe PE, lower risk of bleeding, and fewer in-hospital complications. At 30-day follow-up, there were no differences in all-cause mortality or bleeding. Health coverage by social insurance (OR 7.45, CI 95% 1.74-31.9, p < 0.01) or by private coverage (OR 10.5, CI 95% 2.4-45.9, p < 0.01) were independent predictors of DOAC prescription at discharge, and history of heart failure (OR 0.19, 95% CI 0.04-0.84, p = 0.028) and oncological disease (OR 0.49, 95% CI 0.27-0.89; p = 0.02) were predictors not prescribe them. Conclusions: One in five survivors of acute PE received DOACs at hospital discharge in Argentina, and this was determined by clinical and economic variables.

Predictors of use of direct oral anticoagulants in acute pulmonary embolism.

INTRODUCTION: In the last decade, direct oral anticoagulants (DOACs) have been incorporated as an anticoagulation tool in patients with acute pulmonary thromboembolism (PTE). Although they have a better pharmacological profile than vitamin K antagonists (VKA), the use of these drugs is not massive. The objective of this study was to evaluate the use of DOACs in patients with acute PE and to detect determinants of its use. METHODOLOGY: Prespecified analysis of the CONAREC XX registry that included patients with acute PE in 64 centers in Argentina. An analysis was performed to detect predictors of DOAC prescription at discharge. RESULTS: 579 patients who received anticoagulation at hospital discharge were analyzed: 60% received VKA, 21% heparin and 19% DOAC (of them, 49% Rivaroxaban, 34% Apixaban, and 17% Dabigatran). Patients receiving DOACs had less severe PE, lower risk of bleeding, and fewer in-hospital complications. At 30-day follow-up, there were no differences in all-cause mortality or bleeding. Health coverage by social insurance (OR 7.45, CI 95% 1.74-31.9, p < 0.01) or by private coverage (OR 10.5, CI 95% 2.4-45.9, p < 0.01) were independent predictors of DOAC prescription at discharge, and history of heart failure (OR 0.19, 95% CI 0.04-0.84, p = 0.028) and oncological disease (OR 0.49, 95% CI 0.27-0.89; p = 0.02) were predictors not prescribe them. CONCLUSIONS: One in five survivors of acute PE received DOACs at hospital discharge in Argentina, and this was determined by clinical and economic variables.

INTRODUCCIÓN: En la última década los anticoagulantes orales directos (ACOD) se incorporaron como herramienta para la anticoagulación en pacientes con tromboembolia pulmonar (TEP) aguda. Aunque tienen un mejor perfil farmacológico que los antagonistas de la vitamina K (AVK), el uso de estos fármacos no es masivo. El objetivo del presente trabajo fue evaluar el uso de ACOD en pacientes con TEP aguda y detectar determinantes de su indicación. METODOLOGÍA: Análisis preespecificado del registro CONAREC XX que incorporó pacientes con TEP aguda en 64 centros de Argentina. Se realizó un análisis para detectar predictores de prescripción de ACOD al alta. RESULTADOS: Se analizaron 579 pacientes que recibieron anticoagulación al alta hospitalaria: el 60% recibió AVK, el 21% heparinas y el 19% ACOD (de ellos, un 49% rivaroxabán, un 34% apixabán y un 17% dabigatrán). Los pacientes que recibieron ACOD tenían TEP de menor gravedad, menor riesgo de hemorragia y menos complicaciones intrahospitalarias. En el seguimiento a 30 días no hubo diferencias en mortalidad por todas las causas o sangrados. La cobertura de salud por un seguro social (odds ratio [OR] 7.45; intervalo de confianza del 95% [IC 95%]: 1.74-31.9; p < 0.01) o por cobertura privada (OR 10.5; IC 95%: 2.4-45.9; p < 0.01) fueron predictores independientes de la prescripción de ACOD al alta, y el antecedente de insuficiencia cardiaca (OR 0.19; IC 95%: 0.04-0.84; p = 0.028) y de enfermedad oncológica (OR 0.49; IC 95%: 0.27-0.89; p = 0.02) fueron predictores de no prescribirlos. CONCLUSIONES: Uno de cada cinco supervivientes de TEP aguda recibió ACOD al egreso hospitalario en Argentina, y esto fue determinado por variables clínicas y económicas.

Factors associated with nonadherence to the use of coumarin derivatives or direct oral anticoagulants: A systematic review of observational studies.

Nonadherence to thromboprophylaxis treatment with oral anticoagulants (OAC) is a public health problem and may be associated with high mortality rates. We sought to synthesize the factors associated with nonadherence to therapy with coumarin derivatives or direct oral anticoagulants. A systematic review was performed at electronic databases Medline, Embase, CINAHL, Lilacs and grey literature (Google Scholar, MedNar, OpenGray, ProQuest Dissertations and Theses, and hand search). This study was conducted according to Cochrane's method and PRISMA. The registration on PROSPERO is CRD42020223555. Overall, 1270 studies were identified and nine studies were selected for this review. In hand searching, 77 studies were found, but none included. The associated factors with nonadherence were heterogeneous, and some factors were described as both risk and protection for nonadherence, with few variables showing consistent results among the studies. Variables reported only as risk factors were "male sex", "hospitalization", "Charlson score" and "bleeding", while "white race", CHA2 DS2 VASc (score range 2-9)" and "polypharmacy" were reported only as protective factors. Most studies did not present details in the description of concepts and methods to assess nonadherence. In clinical practice, the knowledge on factors associated with nonadherence is helpful to identifying patients at higher risk of complications that would benefit from individualized interventions.

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.

[MANAGEMENT RECOMMENDATIONS FOR DIRECT ORAL ANTICOAGULANTS (DOACs) ANTI Xa AND ANTI IIa]. / RECOMENDACIONES DE MANEJO DE LOS ANTICOAGULANTES ORALES DIRECTOS (DOACS) ANTI Xa Y ANTI IIa.

Direct oral anticoagulants have emerged as the drugs that have changed the management 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 anticoagulants 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.

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 propiedades 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.

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.

Prescription of oral anticoagulation in geriatric patients with atrial fibrillation / Prescripción de anticoagulación oral en el paciente geriátrico con fibrilación auricular.

Objective: To determine the prevalence of prescription of oral anticoagulation in patients aged > 60 years with nonvalvular atrial fibrillation (NVAF). Methods: Observational, cross-sectional, retrospective study based on a review of the clinical ­histories of patients aged >60 years diagnosed with NVAF from July 1 to September 30, 2019 and seen at the outpatient clinic (cardiology, internal medicine, geriatrics) of a secondary-level hospital in Queretaro, Mexico. Clinical profile and oral anticoagulant treatment were analyzed. Results: The study population comprised 300 patients (mean age, 77.2±8.3 years; 53.3% women; 81% attended in cardiology). Of these, 91% had a high thromboembolic risk, 22.7% a high bleeding risk, and 1.7% contraindications for anticoagulation. Comorbidity was frequent. As for therapy, 82.7% were taking direct oral anticoagulants (DOAC), 11.0% vitamin K antagonists (VKA), and 6.3% no anticoagulant treatment. Anticoagulant therapy was inappropriate in 29.3% of patients, mainly because DOAC were prescribed without adjusting for age, weight, or serum creatinine and administered without indication according to thromboembolic risk. Only 39.4% of patients taking VKA were within the therapeutic range. Of all patients receiving DOAC, 48.0% were taking rivaroxaban, mainly at 20 mg/d (73.1%). Conclusions: Thromboembolic risk is high in geriatric patients with NVAF. Anticoagulation is contraindicated in <2% of patients. Oral anticoagulants are prescribed inappropriately in three out of ten patients.

Objetivo: Determinar la prevalencia de prescripción de anticoagulación oral en pacientes > 60 años con fibrilación auricular no valvular (FANV). Métodos: Estudio observacional, transversal, retrospectivo en el que se revisaron los expedientes de pacientes > 60 años que acudieron a la consulta externa de especialidades (cardiología, medicina interna, geriatría) de un hospital de segundo nivel de atención en Querétaro, México, con el diagnóstico de FANV del 1 de julio al 30 de septiembre de 2019. Se analizaron el perfil clínico y el tratamiento anticoagulante. Resultados: Se incluyeron 300 pacientes (edad media: 77.2 ± 8.3 años; 53.3% mujeres; 81.0% atendidos en cardiología). El 91% presentaban un riesgo tromboembólico elevado, el 22.7% un riesgo hemorrágico elevado y el 1.7% contraindicaciones para la anticoagulación. La presencia de comorbilidades fue frecuente. El 82.7% estaban tomando anticoagulantes orales de acción directa (ACOD), el 11.0% antagonistas de la vitamina K (AVK), y el 6.3% no estaban tomando ningún tratamiento anticoagulante. El 29.3% de los pacientes estaban tomando anticoagulantes orales de manera inadecuada, siendo las dos principales causas la prescripción de dosis de ACOD no ajustada a edad, peso y nivel de creatinina y la administración de ACOD sin indicación de acuerdo con el riesgo tromboembólico. De los pacientes que tomaban AVK, solo el 39.4% presentaban una anticoagulación en rango terapéutico. De los tratados con ACOD, el 48.0% tomaban rivaroxabán, principalmente con una dosis de 20 mg/día (73.1%). Conclusiones: El riesgo tromboembólico en pacientes geriátricos con FANV es elevado. En menos del 2% existe una contraindicación para la anticoagulación. En tres de cada diez pacientes se prescriben de manera inadecuada los anticoagulantes orales.

A network meta-analysis of direct factor Xa inhibitors for the treatment of cancer-associated venous thromboembolism.

INTRODUCTION: Treatment of cancer-associated venous thromboembolism (CAVTE) remains challenging. The aim of this study was to assess the outcomes of direct acting oral anticoagulants (DOAs) for the treatment of CAVTE. MATERIALS AND METHODS: A network meta-analysis of randomized clinical trials comparing DOAs (Apixaban, Rivaroxaban, and Edoxaban) versus Dalteparin for the treatment of CAVTE was performed. Outcomes of interest included, VTE recurrence, all-cause mortality, event-free survival, major bleeding, and clinically relevant non-major bleeding (CRNMB). Analysis was based on a random effects model and Bayesian Markov-chain Monte Carlo method was used for indirect comparisons. RESULTS: Four RCTs involving 2894 patients were included. Overall certainty of evidence was moderate regarding all outcomes. DOAs exhibited lower risk of VTE (RR 0.62; 95% CI 0.44, 0.87; P = 0.007), similar risk of major bleeding (RR 1.33; 95% CI 0.84, 2.11; P = 0.23), and higher risk of CRNMB (RR 1.66, 95% CI 1.08, 2.56; P = 0.02), compared with Dalteparin. Risk of all-cause mortality and event-free survival were similar between groups with RR 0.99 (95% CI 0.84, 1.16) and RR 1.03 (95% CI 0.94, 1.13), respectively. Apixaban ranked first for recurrent VTE (42.4%) and major bleeding (62.3%) and Dalteparin ranked first for CRNMB (54.7%). Rivaroxaban ranked best considering all-cause mortality (58.7%); Apixaban ranked best for event-free survival (83.6%). CONCLUSIONS: DOAs presented a reduced risk of recurrent VTE with similar risk of major bleeding compared to Dalteparin. However, a higher risk of CRNMB is expected when this cohort of patients are treated with DOAs instead of Dalteparin.

Comparison of the Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and Valvular Heart Disease: Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: Direct oral anticoagulants (DOACS) are approved for use in non-valvular atrial fibrillation (AF). This systematic review and meta-analysis aimed to evaluate the efficacy and safety of DOACs vs. warfarin and update the evidence for treatment of AF and valvular heart disease (VHD). Methods: We identified randomized clinical trials (RCTs) and post-hoc analyses comparing the use of DOACS and Warfarin in AF and VHD, including biological and mechanical heart valves (MHV), updating from 2010 to 2020. Through systematic review and meta-analysis, by using the "Rev Man" program 5.3, the primary effectiveness endpoints were stroke and systemic embolism (SE). The primary safety outcome was major bleeding, while the secondary outcome included intracranial hemorrhage. We performed prespecified subgroup analyses. Data were analyzed by risk ratio (RR) and 95% confidence interval (CI) and the I-square (I 2) statistic as a quantitative measure of inconsistency. Risk of bias and methodological quality assessment of included trials was evaluated with the modified Cochrane risk-of-bias tool. Results: We screened 326 articles and included 8 RCTs (n = 14.902). DOACs significantly reduced the risk of stroke/SE (RR 0.80, 95% CI: 0.68-0.94; P = 0.008; moderate quality evidence; I 2 = 2%) and intracranial hemorrhage (RR 0.40, 95% CI: 0.24-0.66; P = 0.0004; I 2 = 49%) with a similar risk of major bleeding (RR 0.83, 95% CI: 0.56-1.24; P = 0.36; I 2 = 88%) compared to Warfarin. Conclusions: In this update, DOACs remained with similar efficacy and safety compared to warfarin in thromboprophylaxis for AF and VHD.

[Direct acting oral anticoagulants versus low molecular weight heparin for primary thromboprophylaxis in cancer patients]. / Anticoagulantes orales de acción directa versus heparina de bajo peso molecular para tromboprofilaxis primaria en pacientes con cáncer.

INTRODUCTION: Low molecular weight heparin is currently the standard therapy for the primary prevention of thromboembolic disease in cancer patients. The use of direct-acting anticoagulants could be an alternative, but its efficacy and safety profile in these types of patients remains unclear. METHODS: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple sources of information, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from identified reviews, analyzed data from primary studies, performed a meta-analysis, and prepared a summary table of results using the GRADE method. RESULTS AND CONCLUSIONS: We identified four systematic reviews that together included two primary studies, of which both correspond to trials. We conclude that the use of direct-acting oral anticoagulants probably increases the outcome of major bleeding and likely slightly increases the risk of thromboembolic disease. No studies were found that evaluated the outcome of quality of life or mortality.

INTRODUCCIÓN: El uso de heparina de bajo peso molecular es actualmente la terapia estándar para prevención primaria de enfermedad tromboembólica en pacientes con cáncer. El uso de los anticoagulantes de acción directa podría ser una alternativa pero su perfil de eficacia y seguridad en este tipo de pacientes sigue siendo aún poco claro. MÉTODOS: Realizamos una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, analizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos cuatro revisiones sistemáticas que, en conjunto, incluyeron dos estudios primarios, los que corresponden a ensayos. Concluimos que el uso de anticoagulantes orales de acción directa probablemente aumenta el desenlace hemorragia mayor y probablemente aumenta levemente el riesgo de enfermedad tromboembólica. No se encontraron estudios que evaluaran el desenlace calidad de vida ni de mortalidad.