Patrones y resultados del cambio de anticoagulantes orales directos en la fibrilación auricular no valvular: experiencia en la práctica clínica en España / Patterns and outcomes of switching direct oral anticoagulants in non-valvular atrial fibrillation: A real-world experience from Spain

Objetivos El objetivo consistía en evaluar un programa de gestión de anticoagulantes orales directos (ACOD) en pacientes con fibrilación auricular no valvular (FANV) según sus perfiles, idoneidad de la dosis, patrones de cambio de tratamiento, efectividad y seguridad Se trató de un estudio observacional, prospectivo y longitudinal en una cohorte de pacientes atendidos en la práctica clínica cotidiana en un hospital regional español con un plan de seguimiento de 3 años para pacientes que iniciaron el tratamiento con dabigatrán, rivaroxabán o apixabán entre enero de 2012 y diciembre de 2016. Métodos Se analizaron 490 episodios de tratamiento (apixabán 2,5mg, 9,4%; apixabán 5mg, 21,4%; dabigatrán 75mg, 0,6%; dabigatrán 110mg, 12,4%; dabigatrán 150mg, 19,8%; rivaroxabán 15mg, 17,8%; rivaroxabán 20mg, 18,6%) en 445 pacientes. En el 13,6% de los pacientes tratados con dabigatrán, el 9,7% de los tratados con rivaroxabán y el 3,9% de los tratados con apixabán se cambió a otros ACOD o se modificó la dosis. Resultados El ACOD al que se cambió con mayor frecuencia fue el apixabán. Los motivos más frecuentes para cambiar de tratamiento fueron toxicidad (23,8%), hemorragia (21,4%) y deterioro renal (16,7%). En el 23,8% de los episodios se constató una inadecuación de la dosis. Las tasas de ictus y accidentes isquémicos transitorios (AIT) fueron de 1,64 y 0,54 eventos/100 años/paciente, respectivamente, mientras que las de hemorragias importantes, no importantes, pero clínicamente relevantes (NICR) e intracraneales fueron de 2,4, 5 y 0,5 eventos/100 años/paciente, respectivamente. Las hemorragias digestivas y genitourinarias fueron el tipo más frecuente de eventos hemorrágicos. En el análisis multifactorial, el ictus previo y la edad fueron factores predictivos independientes de ictus/AIT. El uso concomitante de antiagregantes plaquetarios, el sexo masculino y la edad fueron factores predictivos independientes de eventos hemorrágicos (AU)

Aims The aim is to evaluate a management program for direct oral anticoagulants (DOACs) in non-valvular atrial fibrillation (NVAF) patients according to their profiles, appropriateness of dosing, patterns of crossover, effectiveness and safety. This is an observational and longitudinal prospective study in a cohort of patients attended in daily clinical practice in a regional hospital in Spain with 3-year a follow-up plan for patients initiating dabigatran, rivaroxaban or apixaban between Jan/2012 and Dec/2016. Methods We analyzed 490 episodes of treatment (apixaban 2.5, 9.4%; apixaban 5, 21.4%; dabigatran 75, 0.6%; dabigatran 110, 12.4%; dabigatran 150, 19.8%; rivaroxaban 15, 17.8% and rivaroxaban 20, 18.6%) in 445 patients. 13.6% of patients on dabigatran, 9.7% on rivaroxaban, and 3.9% on apixaban switched to other DOACs or changed dosing. Results Apixaban was the most frequent DOAC switched to. The most frequent reasons for switching were toxicity (23.8%), bleeding (21.4%) and renal deterioration (16.7%). Inappropriateness of dose was found in 23.8% of episodes. Rates of stroke/transient ischemic attack (TIA) were 1.64/0.54 events/100 patients-years, while rates of major, clinically relevant non-major (CRNM) bleeding and intracranial bleeding were 2.4, 5, and 0.5 events/100 patients-years. Gastrointestinal and genitourinary bleeding were the most common type of bleeding events (BE). On multivariable analysis, prior stroke and age were independent predictors of stroke/TIA. Concurrent platelet inhibitors, male gender and age were independent predictors of BE. Conclusion This study complements the scant data available on the use of DOACs in NVAF patients in Spain, confirming a good safety and effectiveness profil (AU)

Efficacy and safety of direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: A systematic review and Bayesian network meta-analysis / Eficacia y seguridad de los anticoagulantes orales directos para el tratamiento de la tromboembolia venosa asociada al cáncer: una revisión sistemática y un metaanálisis en red bayesiana

Introduction: Direct oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4–20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH).Materials and methodsPubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses.ResultsSeven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47–0.82, I2=0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77–2.18, I2=34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17–2.22, I2=20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11–1.74, I2=0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk.ConclusionsCompared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events. (AU)

Introducción: Los anticoagulantes orales directos (ACOD) son eficaces en la prevención de la tromboembolia venosa (TEV) relacionada con el cáncer, cuya tasa de incidencia se estima en 4-20%. Sin embargo, la eficacia y seguridad de ACOD y heparina de bajo peso molecular (HBPM) siguen siendo controvertidas.Materiales y métodosDesde el inicio hasta el 15 de marzo de 2022 se realizaron búsquedas sistemáticas en las bases de datos de ensayos controlados aleatorios (ECA) en PubMed, The Cochrane Library, Embase, ClinicalTrials.gov. Se utilizó el modelo de efectos aleatorios para informar la razón de probabilidades (RP) y los intervalos de confianza (IC) de 95% para los metaanálisis directos y de red.ResultadosSe incluyeron siete estudios con un total de 3.242 pacientes. En comparación con HBPM, los ACOD tienen una tasa más baja de recurrencia de TEV (OR 0,62, IC 95%: 0,47 a 0,82, I2 = 0,0%). La frecuencia de hemorragias mayores fue similar (OR 1,30, IC 95% 0,77 a 2,18, I2 = 34,9%). Se observó un mayor riesgo de eventos en los ACOD. Cuando se evaluaron las hemorragias no mayores clínicamente relevantes (CRNMB) (OR 1,61, IC 95%: 1,17 a 2,22, I2 = 20,7%) y las hemorragias clínicamente relevantes (OR 1,39, IC 95%: 1,11 a 1,74, I2 = 0,0%), En los análisis de subgrupos, las hemorragias mayores en las neoplasias malignas gastrointestinales y genitourinarias fueron más frecuentes con los ACOD. Apixabán ocupó el primer lugar en la prevención de TEV y la reducción de eventos hemorrágicos mayores. Edoxabán tuvo el mayor riesgo de hemorragias mayores. Las HBPM demostraron tener menor riesgo de hemorragias mayores clínicamente relevantes y hemorragias clínicamente relevantes. (AU)

Impact of drug interactions with direct oral anticoagulants on mortality in elderly with atrial fibrillation during the COVID-19 pandemic

Objective: To evaluate the effect of drug interactions with chronic direct oral anticoagulants (DOAC) on mortality in older atrial fibrillation (AF) patients during the Coronavirus disease 2019(COVID-19) pandemic.MethodsWe followed a total of 601 elderly patients (65 years of age) from the NOEL-Drug Registry cohort who were referred to a tertiary outpatient clinic between 9 March 2020 and 1 March 2021. We recorded clinical characteristics and medications for the last 3 months. In addition, all drug interactions were identified using Lexicomp®. Finally, we recorded retrospectively all death events, COVID-19 diagnosis, and relevant deaths from the database at the end of the study. According to logistic regression, we performed propensity score (PS) matching to reduce potential bias. Factors associated with total mortality in the 12 months were analyzed using multivariable Cox proportion hazard analysis.ResultsThe mean age [standard deviation (SD)] was 74.5 (±6.9), and the male/female ratio was 337/264. The prevalence of total mortality was 16.9% (n=102). A total of 4472 drugs were analyzed for DOAC interaction. 81.8% of older AF patients were not at risk in terms of potential interaction. In the Cox proportional hazard model after PS-matching, previous DOAC use with class X interaction was associated with significantly higher mortality risk (adjusted hazard ratio: 2.745, 95% confidence interval: 1.465–5.172, p=0.004).ConclusionsOur study showed that while most co-medications do not have significant interactions with DOACs, few serious drug interactions contribute to mortality in elderly patients with AF during the pandemic. (AU)

Introducción: Evaluar el efecto de las interacciones farmacológicas con anticoagulantes orales directos (ACOD) crónicos sobre la mortalidad en pacientes mayores con fibrilación auricular (FA) durante la pandemia de la enfermedad por coronavirus 2019 (COVID-19).MétodosSeguimos a un total de 601 pacientes ancianos (65años) de la cohorte NOEL-Drug Registry que fueron remitidos a una consulta externa de tercer nivel entre el 9 de marzo de 2020 y el 1 de marzo de 2021. Registramos las características clínicas y los medicamentos durante los últimos tres meses. Además, todas las interacciones medicamentosas se identificaron utilizando Lexicomp®. Finalmente, registramos retrospectivamente todos los eventos de muerte, el diagnóstico de COVID-19 y las muertes relevantes de la base de datos al final del estudio. De acuerdo con la regresión logística, realizamos un emparejamiento por puntaje de propensión (PP) para reducir el posible sesgo. Los factores asociados con la mortalidad total en los 12 meses se analizaron mediante análisis de riesgo de proporción de Cox multivariable.ResultadosLa edad media (desviación estándar [DE]) fue de 74,5 (±6,9) y la relación hombre/mujer, de 337/264. La prevalencia de mortalidad total fue del 16,9% (n=102). Se analizaron un total de 4.472 fármacos para determinar la interacción con ACOD. El 81,8% de los pacientes mayores con FA no estaban en riesgo en términos de interacción potencial. En el modelo de riesgos proporcionales de Cox después del emparejamiento por PP, el uso previo de ACOD con interacción X clase se asoció con un riesgo de mortalidad significativamente mayor (índice de riesgo ajustado: 2,745; intervalo de confianza del 95%: 1,465-5,172; p=0,004). (AU)

Impact of drug interactions with direct oral anticoagulants on mortality in elderly with atrial fibrillation during the COVID-19 pandemic.

OBJECTIVE: To evaluate the effect of drug interactions with chronic direct oral anticoagulants (DOAC) on mortality in older atrial fibrillation (AF) patients during the Coronavirus disease 2019(COVID-19) pandemic. METHODS: We followed a total of 601 elderly patients (65 years of age) from the NOEL-Drug Registry cohort who were referred to a tertiary outpatient clinic between 9 March 2020 and 1 March 2021. We recorded clinical characteristics and medications for the last 3 months. In addition, all drug interactions were identified using Lexicomp®. Finally, we recorded retrospectively all death events, COVID-19 diagnosis, and relevant deaths from the database at the end of the study. According to logistic regression, we performed propensity score (PS) matching to reduce potential bias. Factors associated with total mortality in the 12 months were analyzed using multivariable Cox proportion hazard analysis. RESULTS: The mean age [standard deviation (SD)] was 74.5 (±6.9), and the male/female ratio was 337/264. The prevalence of total mortality was 16.9% (n=102). A total of 4472 drugs were analyzed for DOAC interaction. 81.8% of older AF patients were not at risk in terms of potential interaction. In the Cox proportional hazard model after PS-matching, previous DOAC use with class X interaction was associated with significantly higher mortality risk (adjusted hazard ratio: 2.745, 95% confidence interval: 1.465-5.172, p=0.004). CONCLUSIONS: Our study showed that while most co-medications do not have significant interactions with DOACs, few serious drug interactions contribute to mortality in elderly patients with AF during the pandemic.

Efficacy and safety of direct oral anticoagulants for the treatment of cancer-associated venous thromboembolism: A systematic review and Bayesian network meta-analysis.

INTRODUCTION: Direct oral anticoagulants (DOACs) could effectively prevent the occurrence of cancer-associated venous thromboembolism (CAVTE), which incidence rate was estimated to be 4-20%. But the efficacy and safety remain controversial between DOACs and low molecular weight heparin (LMWH). MATERIALS AND METHODS: PubMed, Cochrane Library, Embase, ClinicalTrials.gov databases for randomized controlled trials (RCTs) were systematically searched from inception to March 15, 2022. A random-effects model was used to report the odds ratio (OR) and 95% confidence interval (CI) for both direct and network meta-analyses. RESULTS: Seven studies were included totaling 3242 patients. A lower rate of recurrence VTE was noted in the DOACs compared with LMWH (OR 0.62, 95% CI 0.47-0.82, I2=0.0%). The aspect of major bleeding (MB) was similar (OR 1.30, 95% CI 0.77-2.18, I2=34.9%). When assessing clinically relevant nonmajor bleeding (CRNMB) (OR 1.61, 95% CI 1.17-2.22, I2=20.7%) and clinically relevant bleeding (CRB) (OR 1.39, 95% CI 1.11-1.74, I2=0.0%), a higher risk of events was observed in DOACs. In subgroup analyses, the MB of gastrointestinal and genitourinary malignancies had a higher rate in the DOACs. For ranking, apixaban ranked the first in prevention of VTE and reducing MB events. Edoxaban had the highest risk drug in MB. In terms of CRNMB and CRB, LMWH showed the lowest risk. CONCLUSIONS: Compared with LMWH, DOACs seemed to have a decreased risk of recurrence VTE while increasing CRNMB and CRB. DOACs and LMWH were equivalent to the aspect of MB, but DOACs had a higher MB risk in patients with gastrointestinal and genitourinary malignancies. Apixaban may be the lowest risk compared to the other DOACs in precaution of VTE and reducing bleeding events.

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.

Los anticoagulantes orales directos en el tratamiento de la enfermedad tromboembólica venosa asociada a cáncer. Evidencias y recomendaciones / Direct oral anticoagulants in the treatment of venous thromboembolic disease associated with cancer. Evidence and recommendations

Revisión en PubMed y Medline hasta el 31 de marzo de 2021 buscando la evidencia disponible sobre el tratamiento de la enfermedad tromboembólica venosa (ETV) con anticoagulantes orales directos (AOD) en pacientes con cáncer. Se incluyen 15 ensayos aleatorios y controlados, 26 revisiones sistemáticas y metaanálisis y 6 guías de práctica clínica.En pacientes con cáncer, los AOD como tratamiento (inicial y a largo plazo) de la ETV son una opción eficaz y segura frente a las heparinas de bajo peso molecular (HBPM). El riesgo de ETV recurrente es menor con AOD, sin que aumente significativamente el riesgo de hemorragia mayor. En comparación con la HBPM, el riesgo de hemorragia no es mayor, pero desde un punto de vista clínicamente relevante es superior. El mayor riesgo de hemorragia en pacientes tratados con AOD parece estar relacionado con un exceso de hemorragia digestiva alta. Además del cáncer gastrointestinal, otras características de alto riesgo asociadas a las complicaciones hemorrágicas son el cáncer urotelial, las interacciones medicamentosas y el uso de medicamentos contra el cáncer asociados con la toxicidad gastrointestinal.Por todo ello, los AOD deben usarse con precaución en pacientes con cáncer y alto riesgo de hemorragia. Las preferencias individuales son otro aspecto relevante al indicar AOD.(AU)

A review (PubMed/Medline) is carried out until March 31, 2021, looking for the available evidence on the treatment of venous thromboembolic disease (VTE) with direct oral anticoagulants (DOA) in cancer patients. It includes 15 randomized and controlled trials, 26 systematic reviews and meta-analyzes, and 6 clinical practice guidelines.In cancer patients, DOAs as treatment (initial and long-term) of VTE are an effective and safe option compared to low-molecular-weight heparins (LMWH). The risk of recurrent VTE is lower with DOA, without significantly increasing the risk of major bleeding. Compared with LMWH, the risk of non-major but clinically relevant bleeding is higher. The increased risk of bleeding in patients treated with DOA appears to be related to excess upper gastrointestinal bleeding. In addition to gastrointestinal cancer, other high-risk characteristics associated with bleeding complications are urothelial cancer, drug interactions, and the use of anticancer drugs associated with gastrointestinal toxicity.Therefore, DOAs should be used with caution in cancer patients and high risk of bleeding. Individual preferences are another relevant aspect when indicating DOA.(AU)

Prediction and treatment of bleeding in patients under anticoagulant treatment. / Predicción y tratamiento de la hemorragia en pacientes anticoagulados.

Major bleeding is a common complication of anticoagulant treatment. Risk assessment tools are relevant in the management of patients with atrial fibrillation and venous thromboembolism. The combination of clinical, biological and genetic markers is incorporated to build predictive scores to help in the decision process about intensity and duration of treatment. The optimal management of bleeding involves the application of predictive scores in combination with anticoagulant reversal strategies.

Experiencia con idarucizumab como agente reversor de dabigatran / Experience with idarucizumab as a reverse agent of dabigatran

Resumen Los anticoagulantes orales directos (AOD), entre ellos dabigatrán, poseen un perfil riesgo-beneficio favorable comparados con warfarina y además no requieren monitoreo del efecto anticoagulante. Sin embargo, en ocasiones de sangrado con amenaza de vida o requerimiento de procedimiento quirúrgico de emergencia, es de gran utilidad revertir inmediatamente el efecto anticoagulante. Idarucizumab, fragmento de un anticuerpo monoclonal humanizado, revierte inmediatamente el efecto de dabigatrán y es actualmente el único agente reversor de un AOD disponible en Argentina. Presentamos una serie de 8 pacientes a los que se les administró idarucizumab para revertir el efecto de dabigatrán. Todos eran mayores de 65 años, recibían 110 o 150 mg cada 12 horas de dabigatrán y 7/8 estaban anticoagulados por fibrilación auricular; tres tenían indicación discutida para AOD y otro, una dosis mayor a la recomendada. Dos requirieron reversión debido a una cirugía de urgencia, y 6 tuvieron sangrado con amenaza de vida: tres hemorragias digestivas y tres sangrados intra-craneanos (en dos ocasiones traumático). En todos los casos se observó normalización de la hemostasia quirúrgica o control de sangrado crítico. No se observaron complicaciones trombóticas posteriores a la administración del antídoto. Dos fallecieron dentro de los 30 días de la administración por causas no relacionadas con la reversión. Ninguno de nuestros pacientes requirió administración de una segunda dosis de idarucizumab. Nuestro resultado es similar a lo informado en la literatura internacional.

Abstract Direct oral anticoagulants (DOACs), among them dabigatran, have a favorable benefit-risk profile compared with warfarin, and no monitoring of the anticoagulant effect is required. However, reversing the anticoagulant effect immediately is very useful in cases of life-threatening bleeding and emergency surgical procedure requirement. Idarucizumab, a humanized monoclonal antibody fragment, is currently the only reversal agent of a DOAC available in Argentina. Idarucizumab immediately reverse the effect of dabigatran. We present a series of 8 real-life clinical cases who received idarucizumab to reverse the effect of dabigatran. All of the patients were older than 65 years, were receiving 110 or 150 mg every 12 hours of dabigatran and 7/8 were anticoagulated because of atrial fibrillation. Three had a debatable indication for DOACs and another, a higher dose than recommended. Two required reversal due to emergency surgery, and 6 cases had life-threatening bleeding: three gastrointestinal hemorrhages and three intracranial bleeding (Two had a head trauma). In all cases normalization of surgical hemostasis or control of critical bleeding was observed. No hemorrhagic or thrombotic complications were observed after antidote administration. Two died within 30 days of administration of idarucizumab, due to causes unrelated to the reversal. None of our patients required administration of a second dose of idarucizumab. Our result is similar to that reported in international literature.

Direct-acting Oral Anticoagulants in Dermatologic Surgery. / Anticoagulantes orales directos en cirugía dermatológica.

Direct-acting oral anticoagulants (DOACs) have emerged as safer, easier-to-manage alternatives to traditional vitamin K antagonists and are used increasingly because they require no monitoring, have a wider therapeutic window, and react less with other drugs. However, there is little consensus on optimal perioperative management when these drugs are used in dermatologic surgery. This article describes the characteristics of DOACs and reviews current evidence on their use in this setting.

Direct oral anticoagulants versus vitamin K antagonists in real-world patients with nonvalvular atrial fibrillation. The FANTASIIA study.

INTRODUCTION AND OBJECTIVES: To compare the long-term results of direct oral anticoagulants (DOAC) vs vitamin K antagonists (VKA) in real-world-patients with nonvalvular atrial fibrillation (NVAF) in a nationwide, prospective study. METHODS: The FANTASIIA registry prospectively included outpatients with AF anticoagulated with DOAC or VKA (per protocol, proportion of VKA and DOAC 4:1), consecutively recruited from June 2013 to October 2014 in Spain. The incidence of major events was analyzed and compared according to the anticoagulant treatment received. RESULTS: A total of 2178 patients were included in the study (mean age 73.8±9.4 years), and 43.8% were women. Of these, 533 (24.5%) received DOAC and 1645 (75.5%) VKA. After a median follow up of 32.4 months, patients receiving DOAC vs those receiving VKA had lower rates of stroke-0.40 (95%CI, 0.17-0.97) vs 1.07 (95%CI,0.79-1.46) patients/y, P=.032-, severe bleedings-2.13 (95%CI, 1.45-3.13) vs 3.28 (95%CI, 2.75-3.93) patients/y; P = .044-, cardiovascular death-1.20 (95%CI, 0.72-1.99) vs 2.45 (95%CI, 2.00-3.00) patients/y; P = .009-, and all-cause death-3.77 (95%CI, 2.83-5.01) vs 5.54 (95%CI, 4.83-6.34) patients/y; P = .016-. In a modified Cox regression model by the Andersen-Gill method for multiple events, hazard ratios for patients receiving DOAC were: 0.42 (0.16-1.07) for stroke; 0.47 (0.20-1.16) for total embolisms; 0.76 (0.50-1.15) for severe bleedings; 0.67 (0.39-1.18) for cardiovascular death; 0.86 (0.62-1.19) for all-cause death, and 0.82 (0.64-1.05) for the combined event consisting of stroke, embolism, severe bleeding, and all-cause death. CONCLUSIONS: Compared with VKA, DOAC is associated with a trend to a lower incidence of all major events, including death, in patients with NVAF in Spain.

[Effectiveness, safety and costs of stroke prevention in non-valvular auricular fibrillation. Study of cohorts matched by Propensity score]. / Efectividad, seguridad y costes de la prevención tromboembólica en fibrilación auricular. Estudio de cohortes apareado por Propensity score.

OBJECTIVE: To analyze the use, effectiveness, safety and costs of stroke prevention in non-valvular atrial fibrillation (AF) in patients initiating treatment with dabigatran or vitamin K antagonists (VKA). SETTING: Primary Care (PC) at the Catalan Health Institute (ICS) in Catalonia, during 2011-2013. PARTICIPANTS: Patients attended in ICS PC centres with a registered diagnosis of AF who initiate dabigatran or VKA. INTERVENTIONS: Not applicable MAIN MEASUREMENTS: Number of prescriptions and reimbursements of dabigatran and VKA, incidence of stroke and haemorrhages, incidence of mortatlity, number of sickness leave, and costs associated to all the previous variables. RESULTS: 14,930 patients were included; 94.6% initiated VKA and 5.4%, dabigatran. Dabigatran patients were younger and with less comorbidity. There were no statistically significant differences between VKA and dabigatran in the risk of stroke, haemorrhages or death. The costs associated to AF management were higher for PC visits in the VKA group, and higher for laboratory and pharmacy in the dabigatran group, although overall costs were not statistically different. CONCLUSIONS: Most patients initiated VKA. We found no differences between VKA and dabigatran in the risk of stroke, haemorrhages or mortality.

Direct Oral Anticoagulants Versus Vitamin K Antagonists in Real-life Patients With Atrial Fibrillation. A Systematic Review and Meta-analysis.

INTRODUCTION AND OBJECTIVES: To assess the effectiveness of direct oral anticoagulants vs vitamin K antagonists in real-life patients with atrial fibrillation. METHODS: A systematic review was performed according to Cochrane methodological standards. The results were reported according to the PRISMA statement. The ROBINS-I tool was used to assess risk of bias. RESULTS: A total of 27 different studies publishing data in 30 publications were included. In the studies with a follow-up up to 1 year, apixaban (HR, 0.93; 95%CI, 0.71-1.20) and dabigatran (HR, 0.95; 95%CI, 0.80-1.13) did not significantly reduce the risk of ischemic stroke vs warfarin, whereas rivaroxaban significantly reduced this risk (HR, 0.83; 95%CI, 0.73-0.94). Apixaban (HR, 0.66; 95%CI, 0.55-0.80) and dabigatran (HR, 0.83; 95%CI, 0.70-0.97) significantly reduced the major bleeding risk vs warfarin, but not rivaroxaban (HR, 1.02; 95%CI, 0.95-1.10), although with a high statistical heterogeneity among studies. Apixaban (HR, 0.56; 95%CI, 0.42-0.73), dabigatran (HR, 0.45; 95%CI, 0.39-0.51), and rivaroxaban (HR, 0.66; 95%CI, 0.49-0.88) significantly reduced the risk of intracranial bleeding vs warfarin. Reduced doses of direct oral anticoagulants were associated with a slightly better safety profile, but with a marked reduction in stroke prevention effectiveness. CONCLUSIONS: Data from this meta-analysis suggest that, vs warfarin, the stroke prevention effectiveness and bleeding risk of direct oral anticoagulants may differ in real-life patients with atrial fibrillation.

[Extended anticoagulant treatment of venous thromboembolic disease with direct oral anticoagulants]. / Tratamiento anticoagulante extendido de la enfermedad tromboembólica venosa con anticoagulantes orales directos.

Direct oral anticoagulants have demonstrated efficacy and safety in the treatment of venous thromboembolic disease. A review is presented of the results of direct oral anticoagulants in the published clinical trials of extended anticoagulant treatment (after the first 3-6 months of treatment) of venous thromboembolic disease.

[Oral anticoagulation therapy in the elderly population with atrial fibrillation. A review article]. / Anticoagulación en población anciana con fibrilación auricular no valvular. Artículo de revisión.

Aging is an important risk factor for patients with atrial fibrillation. The estimated prevalence of atrial fibrillation in patients aged ≥80 years is 9-10%, and is associated with a four to five fold increased risk of embolic stroke, and with an estimated increased stroke risk of 1.45-fold per decade in aging. Older age is also associated with an increased risk of major bleeding with oral anticoagulant therapy. This review will focus on the role of oral anticoagulation with new oral anticoagulants, non-vitamin K antagonist in populations with common comorbid conditions, including age, chronic kidney disease, coronary artery disease, on multiple medication, and frailty. In patients 75 years and older, randomised trials have shown new oral anticoagulants to be as effective as warfarin, or in some cases superior, with an overall better safety profile, consistently reducing rates of intracranial haemorrhages. Prior to considering oral anticoagulant therapy in an elderly frail patient, a comprehensive assessment should be performed to include the risks and benefits, stroke risk, baseline kidney function, cognitive status, mobility and fall risk, multiple medication, nutritional status assessment, and life expectancy.

Tromboc@t Working Group recommendations for management in patients receiving direct oral anticoagulants. / Recomendaciones del Grupo Catalán de Trombosis (Tromboc@t Working Group) para el tratamiento de los pacientes que reciben anticoagulantes orales directos.

BACKGROUND AND OBJECTIVES: In recent years, direct oral anticoagulants (DOACs) have become an alternative to vitamin K antagonists (VKA) for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (NVAF) as well as for prevention and treatment of deep venous thrombosis. Pivotal trials have demonstrated non-inferiority and potential superiority compared to warfarin, which increases the options of anticoagulant treatment. In our setting, the Anticoagulant Treatment Units (ATUs) and Primary Care Centres (PCCs) play an important role in the education, follow-up, adherence control and management in special situations of anticoagulated patients. These considerations have motivated us to elaborate the present consensus document that aims to establish clear recommendations that incorporate the findings of scientific research into clinical practice to improve the quality of care in the field of anticoagulation. MATERIAL AND METHODS: A group of experts from the Catalan Thrombosis Group (TROMBOC@T) reviewed all published literature from 2009 to 2016, in order to provide recommendations based on clinical evidence. RESULTS: As a result of the project, a set of practical recommendations have been established that will facilitate treatment, education, follow-up and management in special situations of anticoagulated patients with ACODs. CONCLUSIONS: Progressive increase in the use of DOACs calls for measures to establish and homogenise clinical management guidelines for patients anticoagulated with DOACs in ATUs and PCCs.

Clinical characteristics and management of patients with atrial fibrillation treated with direct oral anticoagulants according to blood pressure control.

OBJECTIVE: To determine the clinical characteristics and management of hypertensive patients with nonvalvular atrial fibrillation (AF) treated with direct oral anticoagulants (DOACs) according to blood pressure (BP) control. METHODS: For this purpose, data from two observational, cross-sectional and multicenter studies were combined. In both studies, patients on chronic treatment with anticoagulants and that were on current treatment with DOACs at least for 3 months were included. Adequate BP was defined as a systolic BP<140mmHg and a diastolic BP<90mmHg (<140/85mmHg if diabetes). RESULTS: Overall, 1036 patients were included. Of these, 881 (85%) had hypertension that were finally analyzed. The presence of other risk factors and cardiovascular disease was common. Mean BP was 132.6±14.3/75.2±9.2mmHg and 70.5% of patients achieved BP goals. Those patients with a poor BP control had more frequently diabetes, and a history of prior labile INR. Patients had a high thromboembolic risk, but without significant differences according to BP control. By contrast, more patients with a poor BP control had a higher bleeding risk (HAS-BLED ≥3: 24.0% vs 35.4%; P<0.001). HAS-BLED score was an independent predictor of poor BP control (odds ratio 1.435; 95% confidence interval 1.216-1.693; P<0.001). Satisfaction with anticoagulant treatment was independent of BP control. CONCLUSIONS: More than two thirds of our patients with hypertension and AF anticoagulated with DOACs achieve BP targets, what is clearly superior to that reported in the general hypertensive population.

Discrepancies between the use of MDRD-4 IDMS and CKD-EPI equations, instead of the Cockcroft-Gault equation, in the determination of the dosage of direct oral anticoagulants in patients with non-valvular atrial fibrillation. / Discrepancias entre el empleo de las ecuaciones MDRD-4 IDMS y CKD-EPI en vez de la de Cockcroft-Gault en la determinación de la posología de los anticoagulantes orales directos en pacientes con fibrilación auricular no valvular.

BACKGROUND AND OBJECTIVE: Direct oral anticoagulants (DOACs) require dose adjustment according to estimated clearance creatinine (eClCr) using the Cockcroft-Gault (CG) equation. There are discrepancies with the equations that estimate glomerular filtration rate (eGFR). We analyse how the use of the CKD-EPI and MDRD-4 IDMS equations affect the recommended dosage for ACODs. PATIENTS AND METHODS: Retrospective study of patients with non-valvular atrial fibrillation seen at a cardiology clinic between November 2012 and August 2014. Patients were reclassified according to the recommended dosage for dabigatran, rivaroxaban, apixaban and edoxaban, based on the eGFR equation used. Other clinical factors are taken into account, according to the product label. We analysed the percentage of discordance. RESULTS: Four hundred and fifty-four patients, 53.3% men, with a mean age of 68.7±13.8 years were studied. The mean intra-individual differences recorded for the CG equation were 3.9ml/min/1.73m2 with MDRD-4 IDMS (95% CI 1.4-6.4, P=.003) and 11.3ml/min/1.73m2 with CKD-EPI (95% CI 8.9-13.7, P<.001). A gradient is observed in the discordance of the posology (apixaban 1.1%, dabigatran 3.5%, edoxaban 5.7%, rivaroxaban 8.4% with MDRD-4 IDMS). Differences were limited to patients with eClCr<60ml/min and were more evident in≥75 years in which the eGFR equations overestimate renal function. CONCLUSIONS: In patients with non-valvular atrial fibrillation, especially with renal failure and in the elderly, eGFR equations tend to overestimate renal function relative to CG and therefore suggest an overdose of DOACs.

Nuevos anticoagulantes orales y antiagregantes plaquetarios, en el período perioperatorio de cirugía no cardíaca. Parte 1: Nuevos anticoagulantes directos / Novel oral anticoagulants and new platelet antiaggregants, in the perioperative period of non cardiac surgery. Part 1: New direct oral anticoagulants

Due to the high frequency of patients with atrial fibrillation, thromboembolic disease, users of mechanical prosthetic valves, among other pathologies, in addition to their established use and advantages over vitamin K inhibitors, the use of novel oral anticoagulants (NOAC) is becoming more frequent in the perioperative period. The anesthesiologist must consider the thromboembolic risk of the patient, risk of bleeding, the half-life of the NOAC in used, in addition to the patients renal and hepatic function. Rivaroxaban and Apixaban should be suspended according to the risk of surgical bleeding, 24 to 36 hours before a surgery with a low risk of bleeding and 48 hours for high. In the case of Dabigatran, these times should be extended. These drugs are safe in the perioperative period and in most cases, it is not necessary to do a bridging therapy with heparin. The reversal of this type of drugs is also of special interest, currently available with specific methods for dabigatrán. Antidotes for other drugs are being studied. The decision of using a neuraxial block should be evaluated according to the time in which the patient discontinued the drugs and their renal function, specially in the case of Dabigatran.

Por la alta frecuencia de pacientes con fibrilación auricular, enfermedad tromboembólica, usuarios de válvulas protésicas mecánicas, entre otras patologías, además, de su establecido uso y ventajas con respecto a los inhibidores de vitamina K, cada vez es más frecuente el uso de los nuevos anticoagulantes orales (NACO) en el perioperatorio. Su manejo tiene características especiales. Debemos considerar el riesgo tromboembólico del paciente, de sangrado, la vida media del NACO utilizado, además de las funciones depurativas del organismo. Rivaroxaban y apixaban deben ser suspendidos según el riesgo de sangrado quirúrgico, 24 a 36 horas previo a una cirugía de bajo riesgo de sangrado y 48 horas para una de alto riesgo. En el caso del Dabigatrán y por la importancia de la función renal en su eliminación, estos tiempos deben extenderse. Estos fármacos son seguros en el perioperatorio y en la mayor parte de los casos no es necesario hacer terapia puente con heparina. La reversión es también de especial interés. Actualmente, se dispone con métodos específicos para dabigatrán y potenciales antídotos para los otros fármacos. La posibilidad de realizar un bloqueo neuroaxial debe ser evaluado según el tiempo en que el paciente suspendió los medicamentos y su función renal en caso de Dabigatrán.

Trombocitopenia inducida por heparina: Nuevas opciones terapéuticas / Heparin-induced thrombocytopenia. New therapeutical options

La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica mediada por la formación de anticuerpos contra el complejo heparina-factor plaquetario 4 (FP4), caracterizada por la presencia de trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es una complicación poco frecuente pero grave del uso de cualquier tipo de heparina. En tratados con procedimientos cardiovasculares como intervención coronaria percutánea y cirugía de revascularización cardiaca, la prevalencia de anticuerpos es significativamente mayor que en otros escenarios clínicos. El reconocimiento de las características clínicas y de laboratorio permite la suspensión inmediata de la heparina y la instauración de tratamiento anticoagulante alternativo, para evitar la progresión y formación de nuevos trombos y sus complicaciones. En la presente revisión se resumen las diferentes alternativas terapéuticas para la TIH, en particular los anticoagulantes orales directos (DOACS) como el dabigatran, rivaroxaban y apixaban que pueden proporcionar una nueva opción para el tratamiento de TIH.

Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.