Non-valvular atrial fibrillation in patients on peritoneal dialysis, prevalence, treatment and professionals involved.

Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillars for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population. The objective of our study was to know the prevalence, treatment and professionals involved in the management of atrial fibrillation in peritoneal dialysis patients. For this purpose, we performed a descriptive analysis through a survey sent to different peritoneal dialysis units in Spain. A total of 1,403 patients on peritoneal dialysis were included in the study, of whom 186 (13.2%) had non-valvular atrial fibrillation. In addition, the assessment of the scores of thromboembolic and bleeding risks for the indication of oral anticoagulation was mainly carried out by the cardiologist (60% of the units), as well as its prescription (cardiologist 47% or in consensus with the nephrologist 43%). In summary, patients on peritoneal dialysis have a remarkable prevalence of non-valvular atrial fibrillation. Patients frequently receive oral anticoagulation with vitamin K antagonists, as well as direct oral anticoagulants. The data obtained regarding the scores used for the assessment of thromboembolic and bleeding risk, treatment and involvement by Nephrology indicates that there is a need for training and involvement of the nephrologist in this pathology.

Situación actual de los anticoagulantes orales de acción directa en atención primaria de España. Posicionamiento de SEMERGEN en 2023 / Current situation of direct oral anticoagulants in primary care in Spain: Positioning of SEMERGEN in 2023

La anticoagulación oral es clave para disminuir el riesgo de ictus en la fibrilación auricular. Aunque clásicamente los antagonistas de la vitaminaK (AVK) se han empleado para este fin, han sido ampliamente superados por los anticoagulantes orales de acción directa (ACOD), como lo demuestran las evidencias provenientes de los ensayos clínicos, estudios de vida real y poblacionales. De hecho, todas las guías de práctica clínica recomiendan su uso de manera preferencial sobre los AVK. Sin embargo, en España la prescripción de los ACOD está subordinada a un visado de inspección que recoge las condiciones clínicas definidas en el Informe de Posicionamiento Terapéutico de la Agencia Española del Medicamento, y que todavía impone importantes restricciones a su uso, limitando los beneficios del empleo de los ACOD en los pacientes con fibrilación auricular (FA), y generando además inequidades entre las diferentes comunidades autónomas. De hecho, el empleo de los ACOD en España es muy inferior a los países de nuestro entorno. Esto ha provocado que en otros países ha disminuido la incidencia de ictus isquémico a nivel poblacional, junto con una reducción del coste por paciente con FA, pero en España este descenso ha sido discreto. Por todo ello, y en aras de la sostenibilidad del sistema sanitario, pedimos la eliminación del visado para que los ACOD se puedan prescribir de acuerdo a las recomendaciones realizadas por las guías. Además, también apostamos por el refuerzo de la formación y de las decisiones consensuadas con el paciente, siendo el médico de familia un actor clave en la protección del paciente con FA.(AU)

Oral anticoagulation is the key to reduce the risk of stroke in atrial fibrillation. Although vitaminK antagonists (VKA) have classically been used for this purpose, they have been largely overcome by direct oral anticoagulants (DOAC), as demonstrated by evidence from clinical trials, real-life and population studies. In fact, all clinical practice guidelines recommend their use preferentially over VKA. However, in Spain the prescription of DOAC is subordinated to an inspection visa that includes the clinical conditions defined in the Therapeutic Positioning Report of the Spanish Medicines Agency, and that still imposes important restrictions on their use, limiting the benefits of using DOACs in patients with atrial fibrillation (AF), and also generating inequalities between the different autonomous communities. In fact, the use of DOAC in Spain is much lower than that observed in neighboring countries. This has made that while in other countries the incidence of ischemic stroke has decreased at the population level, along with a reduction in the cost per patient with AF, in Spain this decrease has been modest. For all these reasons, and for assuring the sustainability of the health care system, we ask for the elimination of the visa so that DOAC can be prescribed according to the recommendations made by the guidelines. In addition, we are also committed to reinforce medical education and decisions made by consensus with the patient, with the primary care physician acquiring a key role in the protection of the patient with AF.(AU)

Fibrilación auricular no valvular en pacientes en diálisis peritoneal: prevalencia, tratamiento y profesionales implicados / Non-valvular atrial fibrillation in patients on peritoneal dialysis: prevalence, treatment and professionals involved

La fibrilación auricular (FA) es la arritmia crónica más frecuente en pacientes con enfermedad renal crónica (ERC). La anticoagulación oral con antagonistas de la vitamina K (AVK) y actualmente los anticoagulantes orales de acción directa (ACOD) han sido el pilar fundamental para la prevención de eventos tromboembólicos. Sin embargo, no existen ensayos clínicos aleatorizados de su perfil riesgo-beneficio en pacientes con ERC estadio 5 en diálisis peritoneal (DP) y son pocas las evidencias en la literatura sobre esta población. El objetivo del estudio fue conocer la prevalencia, tratamiento y profesionales implicados en el manejo de la FA en DP en nuestro entorno mediante el análisis descriptivo de una encuesta enviada a diferentes unidades de DP de España. Se incluyeron en el estudio 1.403 pacientes en programa de DP, de los cuales 186 (13,2%) presentaban FA no valvular (FANV). Además, observamos que la valoración de los scores para el inicio del tratamiento anticoagulante la realizaba mayoritariamente el cardiólogo (60% de los centros), así como la prescripción de anticoagulación (cardiólogo 47% o en conjunto con el nefrólogo 43%). En conclusión, los pacientes en DP presentan una notable prevalencia de FANV. Reciben frecuentemente anticoagulación oral (ACO) con AVK, así como con ACOD. Los datos obtenidos respecto a las escalas utilizadas para la valoración de riesgo tromboembólico y de sangrado, tratamiento e implicación por parte de Nefrología indican que existe una necesidad de formación e involucramiento del nefrólogo en esta patología.(AU)

Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillar for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population. The objective of our study was to know the prevalence, treatment and professionals involved in the management of atrial fibrillation in peritoneal dialysis patients. For this purpose, we performed a descriptive analysis through a survey sent to different peritoneal dialysis units in Spain. A total of 1403 patients on peritoneal dialysis were included in the study, of whom 186 (13.2%) had non-valvular atrial fibrillation. In addition, the assessment of the scores of thromboembolic and bleeding risks for the indication of oral anticoagulation was mainly carried out by the cardiologist (60% of the units), as well as its prescription (cardiologist 47% in consensus with the nephrologist 43%). In summary, patients on peritoneal dialysis have a remarkable prevalence of non-valvular atrial fibrillation. Patients frequently receive oral anticoagulation with vitamin K antagonists, as well as direct oral anticoagulants. The data obtained regarding the scales used for the assessment of thromboembolic and bleeding risk, treatment and involvement by Nephrology indicates that there is a need for training and involvement of the nephrologist in this pathology.(AU)

[Current situation of direct oral anticoagulants in primary care in Spain: Positioning of SEMERGEN in 2023]. / Situación actual de los anticoagulantes orales de acción directa en atención primaria de España. Posicionamiento de SEMERGEN en 2023.

Oral anticoagulation is the key to reduce the risk of stroke in atrial fibrillation. Although vitaminK antagonists (VKA) have classically been used for this purpose, they have been largely overcome by direct oral anticoagulants (DOAC), as demonstrated by evidence from clinical trials, real-life and population studies. In fact, all clinical practice guidelines recommend their use preferentially over VKA. However, in Spain the prescription of DOAC is subordinated to an inspection visa that includes the clinical conditions defined in the Therapeutic Positioning Report of the Spanish Medicines Agency, and that still imposes important restrictions on their use, limiting the benefits of using DOACs in patients with atrial fibrillation (AF), and also generating inequalities between the different autonomous communities. In fact, the use of DOAC in Spain is much lower than that observed in neighboring countries. This has made that while in other countries the incidence of ischemic stroke has decreased at the population level, along with a reduction in the cost per patient with AF, in Spain this decrease has been modest. For all these reasons, and for assuring the sustainability of the health care system, we ask for the elimination of the visa so that DOAC can be prescribed according to the recommendations made by the guidelines. In addition, we are also committed to reinforce medical education and decisions made by consensus with the patient, with the primary care physician acquiring a key role in the protection of the patient with AF.

ACOD frente a AVK en pacientes con fibrilación auricular y bioprótesis: revisión sistemática y metanálisis / DOAC versus VKA in patients with atrial fibrillation and bioprosthetic valves: a systematic review and meta-analysis

Introducción y objetivos: Los anticoagulantes orales directos (ACOD) se han mostrado eficaces y seguros en pacientes con fibrilación auricular; sin embargo, los pacientes con FA y bioprótesis están infrarrepresentados en los ensayos clínicos, por lo que la evidencia en este grupo es menor. Nuestro objetivo fue analizar la seguridad y eficacia de los ACODs en esta población revisando la información existente en la literatura. Métodos: Se realizó una búsqueda y revisión sistemática con los ensayos clínicos aleatorizados y estudios observacionales comparativos desde 2017 a enero de 2022, que comparasen ACODs y antagonistas de vitamina K (AVK) en pacientes con FA y bioprótesis. Se utilizó la hazard ratio al 95% del intervalo de confianza para comparar ambos grupos en términos de mortalidad total y cardiovascular, ictus/embolia sistémica y hemorragia mayor. Se realizó un metanálisis combinando los resultados de los estudios incluidos. Resultados: Se incluyeron 12 estudios (un total de 30.283 pacientes). Los ACODs se asociaron a una reducción significativa del 9% de la mortalidad total (HR=0,91; IC95%, 0,85-0,97; p=0,0068; I2=8%), sin diferencias significativas en el riesgo de ictus/embolismo sistémico (HR=0,87; IC95%, 0,67-1,14; p=0,29; I2=45%) o hemorragia mayor (HR=0,82; IC95%, 0,67-1,00; p=0,054; I2=48.7%). Conclusiones: En pacientes con FA portadores de bioprótesis, los ACODs podrían asociarse a una reducción de la mortalidad total sin reducción de eficacia en la prevención de ictus/embolia sistémica o aumento del riesgo de hemorragia mayor.(AU)

Introduction and objectives: Direct oral anticoagulant (DOAC) therapy has been shown to be safe and effective in patients with atrial fibrillation (AF). However, outcomes in AF patients with bioprosthetic valves are unclear, as this population has been underrepresented in clinical trials. The aim of this study was to assess the safety and efficacy of DOACs in this population based on the existing published literature. Methods: A systematic search and review were conducted to identify randomized clinical trials and comparative observational studies published from 2017 to January 2022 that compared DOACs and vitamin K antagonists (VKAs) in AF patients with bioprosthetic valves. Hazard ratios (HR) were collected to compare the 2 treatments in terms of cardiovascular and all-cause mortality, stroke/systemic embolism, and major bleeding. A meta-analysis combining the results was performed. Results: We included 12 studies (30 283 patients). DOACs and VKAs were compared based on HRs at the 95% confidence interval. DOAC therapy was associated with a significant 9% reduction in all-cause mortality (HR, 0.91; 95%CI, 0.85-0.97; P=.0068; I2=8%), with no significant differences in the risk of stroke/systemic embolism (HR, 0.87; 95%CI, 0.67-1.14; P=.29; I2=45%) or major bleeding (HR, 0.82; 95%CI, 0.67-1.00; P=.054; I2=48.7%). Conclusions: DOAC therapy in AF patients with bioprosthetic valves may be associated with a significant reduction in all-cause mortality, with no reduction in the efficacy of stroke/systemic embolism prevention or increase in major bleeding risk.(AU)

DOAC versus VKA in patients with atrial fibrillation and bioprosthetic valves: a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: Direct oral anticoagulant (DOAC) therapy has been shown to be safe and effective in patients with atrial fibrillation (AF). However, outcomes in AF patients with bioprosthetic valves are unclear, as this population has been underrepresented in clinical trials. The aim of this study was to assess the safety and efficacy of DOACs in this population based on the existing published literature. METHODS: A systematic search and review were conducted to identify randomized clinical trials and comparative observational studies published from 2017 to January 2022 that compared DOACs and vitamin K antagonists (VKAs) in AF patients with bioprosthetic valves. Hazard ratios (HR) were collected to compare the 2 treatments in terms of cardiovascular and all-cause mortality, stroke/systemic embolism, and major bleeding. A meta-analysis combining the results was performed. RESULTS: We included 12 studies (30 283 patients). DOACs and VKAs were compared based on HRs at the 95% confidence interval. DOAC therapy was associated with a significant 9% reduction in all-cause mortality (HR, 0.91; 95%CI, 0.85-0.97; P=.0068; I2=8%), with no significant differences in the risk of stroke/systemic embolism (HR, 0.87; 95%CI, 0.67-1.14; P=.29; I2=45%) or major bleeding (HR, 0.82; 95%CI, 0.67-1.00; P=.054; I2=48.7%). CONCLUSIONS: DOAC therapy in AF patients with bioprosthetic valves may be associated with a significant reduction in all-cause mortality, with no reduction in the efficacy of stroke/systemic embolism prevention or increase in major bleeding risk.

Fibrilación auricular no valvular en pacientes en hemodiálisis crónica. ¿Debemos anticoagular? / Nonvalvular atrial fibrillation in patients undergoing chronic hemodialysis. Should dialysis patients with atrial fibrillation receive oral anticoagulation?

La enfermedad renal crónica (ERC) es un factor de riesgo independiente para presentar fibrilación auricular (FA) lo que condiciona un incremento del riesgo ya presente en la ERC de sufrir un evento tromboembólico; y este riesgo es mayor aún en la población en hemodiálisis (HD). Por otro lado, en estos pacientes también es mayor la probabilidad de sufrir una hemorragia grave. Por ello, decidir si se debe anticoagular o no a un paciente con FA en diálisis es motivo de controversia entre la comunidad nefrológica.Tomando como modelo lo aconsejado para la población general, la actitud más común entre los nefrólogos ha sido la de optar por la anticoagulación, pese a que no haya estudios randomizados que lo apoyen.Clásicamente la anticoagulación se ha hecho con antagonistas de la vitamina K, con alto coste para nuestros pacientes: eventos hemorrágicos graves, calcificación vascular y progresión de la nefropatía entre otras complicaciones.Con el surgimiento de los anticoagulantes de acción directa, se abrió un panorama esperanzador en el campo de la anticoagulación, al postularse como fármacos más eficaces y seguros que los antivitamina K. Sin embargo, en la práctica clínica, esto no ha sido así.En esta revisión repasamos diversos aspectos de la FA y de su tratamiento anticoagulante en la población en HD. (AU)

Chronic kidney disease (CKD) is an independent risk factor for presenting atrial fibrillation (AF), which conditions an increased risk already present in CKD of suffering a thromboembolic event. And this risk is even higher in the hemodialysis (HD) population. On the other hand, in CKD patients and even more so in HD patients, the probability of suffering serious bleeding is also higher. Therefore, there is no consensus on whether or not to anticoagulate this population.Taking as a model what is advised for the general population, the most common attitude among nephrologists has been to opt for anticoagulation, even though there are no randomized studies to support it.Classically, anticoagulation has been done with vitamin K antagonists, at high cost for our patients: severe bleeding events, vascular calcification, and progression of nephropathy, among other complications.With the emergence of direct-acting anticoagulants, a hopeful outlook was opened in the field of anticoagulation, as they were postulated as more effective and safer drugs than antivitamin K. However, in clinical practice, this has not been the case.In this paper we review various aspects of AF and its anticoagulant treatment in the HD population. (AU)

Characteristics and management of patients with stroke and major hemorrhagic episodes with atrial fibrillation under vitamin K antagonist therapy. EVENTHO study

Introduction and objective: In Spain, vitamin K antagonists (VKA) remain the standard treatment for the prevention of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF), despite the high risks of suffering adverse effects. The objective of this study was to characterize the profile of VKA-treated patients suffering from stroke/systemic embolism (SE) or major hemorrhagic episodes, their evolution and the actions taken after those episodes.Materials and methodsEVENTHO was an observational multicenter study conducted in 22 Anticoagulation Spanish Units. The study included patients ≥18 years with AF who suffered major hemorrhagic episodes (67.8%) or stroke/SE (32.1%) during 2016 whileon VKA treatment [acenocoumarol (98.2%) or warfarin (1.8%)]. Time in therapeutic range (TTR) was calculated according to the Rosendaal method based on the international normalized ratio (INR) values of the previous 6 months.ResultsThe study included 585 patients (median age [range] 82.3 [43.6–96.2] years; 51.1% men; mean [95% confidence interval, CI] CHA2DS2-VASc: 4.3 [4.2–4.4] and HAS-BLED: 2.2 [2.1–2.3]). Poor anticoagulation and VKA maintenance were higher in patients with major hemorrhagic episode (p<0.0001). The most common situations after hospital discharge were: functional dependence, neurological sequelae and death.ConclusionsIn the sample studied, half of the AF patients who suffered stroke/SE or major hemorrhagic episode had inadequate TTR and, despite this, after hospital discharge, they restarted treatment with VKA. These results highlight the need to evaluate safer and effective therapeutic alternatives in AF patients with poor TTR control after suffering a stroke/SE or major hemorrhagic episode. (AU)

Introducción y objetivo: En España, los antagonistas de la vitamina K (AVK) siguen siendo el tratamiento estándar para la prevención de las complicaciones tromboembólicas y hemorrágicas en pacientes con fibrilación auricular (FA), a pesar del alto riesgo de presentar efectos adversos. El objetivo de este estudio fue caracterizar el perfil de los pacientes tratados con AVK que experimentaron un ictus/embolia sistémica o hemorragia mayor, su evolución y las acciones realizadas tras esos episodios.Materiales y métodosEVENTHO fue un estudio multicéntrico observacional realizado en 22 unidades españolas de anticoagulación. Se incluyó en el estudio a pacientes≥18 años con FA que habían tenido hemorragia mayor (67,8%) o ictus/embolia sistémica (32,1%) durante 2016 y estaban en tratamiento con AVK (acenocumarol [98,2%] o warfarina [1,8%]). El tiempo en rango terapéutico (TRT) se calculó según el método de Rosendaal basado en los valores del índice internacional normalizado de los 6 meses previos.ResultadosEl estudio incluyó a 585 pacientes (edad mediana 82,3 [rango 43,6-96,2] años; 51,1% hombres; CHA2DS2-VASc medio 4,3 [IC 95% 4,2-4,4] y HAS-BLED medio 2,2 [IC 95% 2,1-2,3]). La mala anticoagulación y el mantenimiento de los AVK fueron mayores en los pacientes con hemorragia mayor (p<0,0001). Las situaciones más frecuentes tras el alta hospitalaria fueron: dependencia funcional, secuelas neurológicas y muerte.ConclusionesEn la muestra estudiada, la mitad de los pacientes con FA que tuvieron ictus/embolia sistémica o hemorragia mayor presentaban un TRT inadecuado y, a pesar de ello, tras el alta hospitalaria, reiniciaron el tratamiento con AVK. Estos resultados destacan la necesidad de evaluar alternativas terapéuticas más seguras y eficaces en pacientes con FA con mal control del TRT tras sufrir un ictus/embolia sistémica o hemorragia mayor. (AU)

Gender differences in antithrombotic treatment in patients with atrial fibrillation from Spain versus the rest of Western Europe. GLORIA-AF Program

Background and objective:Thromboembolic risk is higher in women than men with non-valvular atrial fibrillation (NVAF). Published data indicate variability in antithrombotic use by gender and region. We analyzed gender-specific antithrombotic treatment patterns in Spain and rest of Western Europe (rWE) in patients with NVAF.Methods:GLORIA-AF (Phase III) is a global, prospective, observational study which enrolled newly diagnosed NVAF patients with CHA2DS2-VAScs≥1 (2014–2016). Analyses were performed comparing antithrombotic treatments by gender in Spain and rWE.Results:This analysis included 1163 and 7972 patients from Spain and rWE, respectively. Stroke risk was higher in women than men in both Spain and rWE. While in rWE, bleeding risk and antithrombotic treatment pattern were similar between genders, in Spain bleeding risk in women was lower and more females compared to men received OACs (95.0% versus 92.4%, d=−0.1078, respectively). Fewer Spanish patients received direct oral anticoagulants (DOACs) (women 32.1%, men 25.3%) than vitamin-K-antagonists (VKAs) (women 63.0%, men 67.1%) vs. rWE patients. In Spain women received more DOACs compared to men (56.0% versus 44.0%).Conclusions:OAC rates were higher in Spain as compared to rWE. More women received OACs in Spain, while in rWE no difference by gender was observed. DOACs in rWE are the most prescribed OAC while in Spain, due to prescription barriers, its use remains low for both genders and VKAs are preferred. Spanish women received more DOACs compared to men. (NCT01468701). (AU)

Antecedentes y objetivo:El riesgo tromboembólico es mayor en mujeres que en varones con fibrilación auricular no valvular (FANV). Existen diferencias en el uso de anticoagulantes (ACO) según sexo y zona geográfica. Se estudiaron los patrones de anticoagulación por sexo en España y el resto de Europa Occidental (rEO) en pacientes con FANV.Métodos:GLORIA-AF es un estudio observacional prospectivo (fase III) que incluyó a pacientes con diagnóstico reciente de FANV y CHA2DS2-VASc>1 (2014-2016). Se analizó la prescripción de anticoagulantes por sexo en España y el rEO.Resultados:Se incluyó a 1.163 pacientes de España y 7.972 del rEO. El riesgo de ictus fue superior en mujeres tanto en España como en el rEO. El riesgo de hemorragia y el tratamiento antitrombótico fueron similares en ambos sexos en el rEO; en España, el riesgo de hemorragia fue menor en mujeres y estas recibieron más ACO que los varones (95,0% vs. 92,4%, d=–0,1078). En España, menos pacientes recibieron ACO directos (ACOD) (mujeres 32,1%, varones 25,3%) vs. antagonistas de la vitamina K (AVK) (mujeres 63,0%, varones 67,1%), y las mujeres recibieron más ACOD que los varones (56,0% vs. 44,0%).Conclusiones:En España se emplearon más ACO que en el rEO y más mujeres fueron tratadas con ACO, mientras que en el rEO no hubo diferencias por sexo. En el rEO, los ACOD se emplearon más. En España, los ACOD se emplean menos por restricciones de prescripción y se emplean más los AVK. Las mujeres españolas reciben más ACOD que los varones. (NCT01468701). (AU)

Función de las vitaminas D, E y K en condiciones especiales: salud y enfermedad / Function of vitamins D, E and K in Special Conditions: Health and Disease

Resumen: Antecedentes: se cuenta con recomendaciones de energía y nutrientes para población sana; sin embargo, a nutrientes como las vitaminas D, E, K se les atribuyen funciones importantes en diferentes situaciones de salud. Objetivo: explorar la efectividad de dosis dietarias y de suplementos de las vitaminas D, E y K en condiciones especiales de salud y enfermedad. Materiales y métodos: se realizó una búsqueda de documentos en las bases de datos PubMed, Scopus, ScienceDirect, Lilacs, SciELO, Ebsco y en textos especializados utilizando palabras clave: "vitamin D", "vitamin E", "vitamin K", "health", "disease", "nutritional recommendations". Resultados: hay un importante número de estudios y revisiones sistemáticas que contribuyen a la evidencia y la discusión en cuanto a efecto, dosis y tiempo, los cuales arrojaron tanto desenlaces positivos como nulos. Conclusión: los efectos de la vitamina D dietaria en la salud ósea están bien documentados, y sus suplementos acompañados de calcio están indicados en grupos poblacionales con riesgo de osteoporosis, pero no en otras condiciones clínicas. No hay suficiente evidencia sobre los beneficios de la vitamina E en el manejo o prevención de enfermedad hepática, cardiovascular o cáncer. La vitamina K podría ser importante en la salud ósea, sobre otras condiciones clínicas.

Abstract: Background: There are energy and nutrient recommendations for a healthy population; however, important functions in different health situations are attributed to nutrients such as vitamins D, E, K, E and K. Objective: To explore the effectiveness of dietary doses and supplements of vitamins D, E and K in special conditions of health and disease. Materials and Methods: A document search was carried out in the PubMed, Scopus, Sciencedirect, Lilacs, Scielo and Ebsco databases, and in specialized texts using keywords: "vitamin D", "vitamin E", "vitamin K", "Health", "disease", "nutritional recommendations". Results: There is a significant number of studies and systematic reviews that contribute to the evidence and discussion regarding effect, dose and time, which yielded both positive and null outcomes. Conclusion: The effects of dietary vitamin D in bone health are well documented and its supplementation accompanied by calcium is indicated in population groups at risk for osteoporosis, but not in other clinical conditions. There is insufficient evidence on the benefits of vitamin E in the management or prevention of liver disease, cardiovascular disease, or cancer. Vitamin K could be important in bone health, over other clinical conditions.

Characteristics and management of patients with stroke and major hemorrhagic episodes with atrial fibrillation under vitamin K antagonist therapy. EVENTHO study.

INTRODUCTION AND OBJECTIVE: In Spain, vitamin K antagonists (VKA) remain the standard treatment for the prevention of thromboembolic and hemorrhagic complications in patients with atrial fibrillation (AF), despite the high risks of suffering adverse effects. The objective of this study was to characterize the profile of VKA-treated patients suffering from stroke/systemic embolism (SE) or major hemorrhagic episodes, their evolution and the actions taken after those episodes. MATERIALS AND METHODS: EVENTHO was an observational multicenter study conducted in 22 Anticoagulation Spanish Units. The study included patients ≥18 years with AF who suffered major hemorrhagic episodes (67.8%) or stroke/SE (32.1%) during 2016 whileon VKA treatment [acenocoumarol (98.2%) or warfarin (1.8%)]. Time in therapeutic range (TTR) was calculated according to the Rosendaal method based on the international normalized ratio (INR) values of the previous 6 months. RESULTS: The study included 585 patients (median age [range] 82.3 [43.6-96.2] years; 51.1% men; mean [95% confidence interval, CI] CHA2DS2-VASc: 4.3 [4.2-4.4] and HAS-BLED: 2.2 [2.1-2.3]). Poor anticoagulation and VKA maintenance were higher in patients with major hemorrhagic episode (p<0.0001). The most common situations after hospital discharge were: functional dependence, neurological sequelae and death. CONCLUSIONS: In the sample studied, half of the AF patients who suffered stroke/SE or major hemorrhagic episode had inadequate TTR and, despite this, after hospital discharge, they restarted treatment with VKA. These results highlight the need to evaluate safer and effective therapeutic alternatives in AF patients with poor TTR control after suffering a stroke/SE or major hemorrhagic episode.

Nonvalvular atrial fibrillation in patients undergoing chronic hemodialysis. Should dialysis patients with atrial fibrillation receive oral anticoagulation?

Chronic kidney disease (CKD) is an independent risk factor for presenting atrial fibrillation (AF), which conditions an increased risk already present in CKD of suffering a thromboembolic event. And this risk is even higher in the hemodialysis (HD) population. On the other hand, in CKD patients and even more so in HD patients, the probability of suffering serious bleeding is also higher. Therefore, there is no consensus on whether or not to anticoagulate this population. Taking as a model what is advised for the general population, the most common attitude among nephrologists has been to opt for anticoagulation, even though there is no randomized studies to support it. Classically, anticoagulation has been done with vitamin K antagonists, at high cost for our patients: severe bleeding events, vascular calcification, and progression of nephropathy, among other complications. With the emergence of direct-acting anticoagulants, a hopeful outlook was opened in the field of anticoagulation, as they were postulated as more effective and safer drugs than antivitamin K. However, in clinical practice, this has not been the case. In this paper we review various aspects of AF and its anticoagulant treatment in the HD population.

Gender differences in antithrombotic treatment in patients with atrial fibrillation from Spain versus the rest of Western Europe. GLORIA-AF Program.

BACKGROUND AND OBJECTIVE: Thromboembolic risk is higher in women than men with non-valvular atrial fibrillation (NVAF). Published data indicate variability in antithrombotic use by gender and region. We analyzed gender-specific antithrombotic treatment patterns in Spain and rest of Western Europe (rWE) in patients with NVAF. METHODS: GLORIA-AF (Phase III) is a global, prospective, observational study which enrolled newly diagnosed NVAF patients with CHA2DS2-VAScs≥1 (2014-2016). Analyses were performed comparing antithrombotic treatments by gender in Spain and rWE. RESULTS: This analysis included 1163 and 7972 patients from Spain and rWE, respectively. Stroke risk was higher in women than men in both Spain and rWE. While in rWE, bleeding risk and antithrombotic treatment pattern were similar between genders, in Spain bleeding risk in women was lower and more females compared to men received OACs (95.0% versus 92.4%, d=-0.1078, respectively). Fewer Spanish patients received direct oral anticoagulants (DOACs) (women 32.1%, men 25.3%) than vitamin-K-antagonists (VKAs) (women 63.0%, men 67.1%) vs. rWE patients. In Spain women received more DOACs compared to men (56.0% versus 44.0%). CONCLUSIONS: OAC rates were higher in Spain as compared to rWE. More women received OACs in Spain, while in rWE no difference by gender was observed. DOACs in rWE are the most prescribed OAC while in Spain, due to prescription barriers, its use remains low for both genders and VKAs are preferred. Spanish women received more DOACs compared to men. (NCT01468701).

Mortalidad en una cohorte de pacientes de Atención Primaria tratados con anticoagulantes antagonistas de la vitamina K / Mortality in a cohort of primary care patients treated with vitamin K antagonist anticoagulants

Introducción y objetivos: El uso de anticoagulantes para prevenir eventos embólicos en España es muy elevado, tendiendo a un aumento progresivo. Por ello pretendemos analizar la mortalidad de los pacientes tratados con anticoagulantes antagonistas de la vitamina K (AVK) de un área metropolitana de Granada, en 2 años no consecutivos.Pacientes y métodos: Estudio longitudinal, observacional, retrospectivo de 205 pacientes tratados con AVK. Se recogieron datos sociodemográficos, condiciones clínicas previas, patología causante del tratamiento AVK, grado de control y la mortalidad a 2 años del inicio del estudio.ResultadosEdad media, 76±11,8años (57,56% mujeres). La mortalidad a los 2 años fue del 22,4%, con un aumento significativo en función de la edad (p<0,001) y los años de tratamiento (p<0,001). Los pacientes con demencia (p<0,05), con enfermedad renal crónica (p<0,01) o con enfermedad pulmonar obstructiva crónica (p<0,01) presentaron también mayor mortalidad. El análisis multivariante demostró efecto significativo de la enfermedad renal crónica (odds ratio=4,075), la enfermedad pulmonar obstructiva crónica (odds ratio=3,694) y los años de tratamiento (odds ratio=1,236).ConclusionesA los 2 años de seguimiento, fallecieron uno de cada 5 pacientes tratados con AVK y se asociaron independientemente a este aumento la presencia de enfermedad renal crónica, enfermedad pulmonar obstructiva crónica y un mayor tiempo de tratamiento. La mayoría de los pacientes estaban anticoagulados por una fibrilación auricular, tenían una edad avanzada y una alta prevalencia de comorbilidades. (AU)

Introduction and objectives: The use of anticoagulants to prevent embolic events in Spain is very high, tending to a progressive increase. For this reason, we intend to analyse the mortality of patients from a metropolitan area of Granada treated with vitamin K antagonist anticoagulants (VKA), over 2 non-consecutive years.Patients and methods: Longitudinal, observational, retrospective study of 205 patients treated with VKA. Sociodemographic data, previous clinical conditions, pathology causing VKA treatment, degree of control and mortality were collected 2 years after the start of the study.ResultsAverage age, 76±11.8 years (57.56% women). Two-year mortality was 22.4%, with a significant increase depending on age (p<.001) and years of treatment (p<.001). Patients with dementia (p<.05), with chronic kidney disease (p<.01) or with chronic obstructive pulmonary disease (p<.01) also presented higher mortality. Multivariate analysis showed significant effect of chronic kidney disease (odds ratio=4.075), chronic obstructive pulmonary disease (odds ratio=3.694), and years of treatment (odds ratio=1.236).ConclusionsAt 2 years of follow-up, 1 in 5 patients treated with VKA died. The presence of chronic kidney disease, chronic obstructive pulmonary disease and a longer treatment time were independently associated with this increase of mortality. Most of the patients were anticoagulated by atrial fibrillation, they were elderly and had a high prevalence of comorbidities. (AU)

Analysis of the quality of anticoagulation with vitamin K antagonists in three clinical scenarios in Mexico.

INTRODUCTION: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. OBJECTIVE: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. METHODS: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. RESULTS: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. CONCLUSIONS: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.

INTRODUCCIÓN: Los antagonista de la vitamina K (AVK) son una alternativa terapéutica en los pacientes con enfermedad tromboembólica venosa; sin embargo, numerosos factores afectan su farmacología. OBJETIVO: Evaluar la calidad de la anticoagulación AVK durante tres diferentes periodos en México. MÉTODOS: Estudio prospectivo, anidado en cohortes de pacientes en tres escenarios clínicos entre los años 2013-2019. Se incluyeron pacientes no hospitalizados con indicación para recibir AVK por al menos 12 meses, quienes fueron manejados de acuerdo con el criterio del médico tratante. RESULTADOS: Las características generales de los pacientes fueron similares entre los grupos, excepto por la indicación para usar los AVK. Se analizaron los resultados de 4148 pacientes y 38 548 evaluaciones de INR. Los tiempos en rango terapéutico durante las tres fases del estudio y los datos acumulados fueron significativamente mayores en la clínica de anticoagulación. Solo el número de visitas de control de los pacientes se asoció significativamente con los resultados, a diferencia de la edad, el sexo y el tipo de AVK. CONCLUSIONES: Los AVK se utilizan ampliamente, pero es difícil alcanzar la meta terapéutica, sobre todo en servicios clínicos no especializados. La creación de clínicas de anticoagulación es una necesidad urgente en el sistema mexicano de salud.

Análisis farmacogenético retrospectivo de una paciente pediátrica en tratamiento anticoagulante: caso clínico / Retrospective pharmacogenetic analysis of a pediatric patient under anticoagulant treatment: Clinical case

Se presenta el caso clínico de una paciente de 10 años diagnosticada con miocardiopatía dilatada, quien registró valores en el índice internacional normalizado (International Normalized Ratio, INR) superiores a 10 con la dosis estándar de acenocumarol, además de otros valores que indicaban el estado incoagulable, lo que obligó a suspender y reiniciar el tratamiento en varias ocasiones. Después de más de 30 días de tratamiento, sorprendentemente se lograron los niveles esperados y estables en el INR con la mitad de la dosis recomendada para una paciente de su edad y peso.Se decidió hacer un análisis farmacogenético retrospectivo del caso mediante RT-PCR con sondas TaqMan™ que incluyó cinco polimorfismos de un solo nucleótido y distinto grado de asociación con la dosis-respuesta a los fármacos antivitamínicos K (AVK): rs2108622 (gen CYP4F2), rs9923231, rs7294 (gen VKORC1), rs1799853 y rs1057910 (gen CYP2C9). La paciente resultó ser homocigota para el rs9923231 (VKORC1) y heterocigota para el rs2108622 (CYP4F2). Se ha evidenciado a nivel nacional e internacional que este perfil genético está fuertemente asociado con una necesidad de dosis menores de antivitamínicos K.En conclusión, el análisis farmacogenético confirmó que la condición genética de la paciente, la cual conlleva una baja expresión de la enzima VKORC1 (blanco terapéutico de los antivitamínicos K), hacía predecible la necesidad de una dosis menor a la establecida según los protocolos clínicos recomendados por la Food and Drug Administration (FDA) y PharmGKB™ para los fármacos cumarínicos. El análisis genotípico previo de la paciente hubiese permitido alcanzar el rango terapéutico más prontamente, evitando potenciales riesgos de hemorragia, lo que demuestra la importancia de los análisis farmacogenéticos en tratamientos de gran variabilidad y estrecho rango terapéutico.

Abstract We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2), a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence. In conclusion, the pharmacogenetic analysis confirmed that this patient's genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range.

Análisis de la calidad de la anticoagulación con antagonistas de la vitamina K en tres escenarios clínicos en México / Analysis of the quality of anticoagulation with vitamin K antagonists in three clinical scenarios in Mexico

Resumen Introducción: Los antagonista de la vitamina K (AVK) son una alternativa terapéutica en los pacientes con enfermedad tromboembólica venosa; sin embargo, numerosos factores afectan su farmacología. Objetivo: Evaluar la calidad de la anticoagulación AVK durante tres diferentes periodos en México. Métodos: Estudio prospectivo, anidado en cohortes de pacientes en tres escenarios clínicos entre los años 2013-2019. Se incluyeron pacientes no hospitalizados con indicación para recibir AVK por al menos 12 meses, quienes fueron manejados de acuerdo con el criterio del médico tratante. Resultados: Las características generales de los pacientes fueron similares entre los grupos, excepto por la indicación para usar los AVK. Se analizaron los resultados de 4148 pacientes y 38 548 evaluaciones de INR. Los tiempos en rango terapéutico durante las tres fases del estudio y los datos acumulados fueron significativamente mayores en la clínica de anticoagulación. Solo el número de visitas de control de los pacientes se asoció significativamente con los resultados, a diferencia de la edad, el sexo y el tipo de AVK. Conclusiones: Los AVK se utilizan ampliamente, pero es difícil alcanzar la meta terapéutica, sobre todo en servicios clínicos no especializados. La creación de clínicas de anticoagulación es una necesidad urgente en el sistema mexicano de salud.

Abstract Introduction: Vitamin K antagonists (VKA) are a therapeutic alternative in patients with venous thromboembolic disease; however, numerous factors affect their pharmacology. Objective: To evaluate the quality of VKA anticoagulation at three different time periods in Mexico. Methods: Prospective study, nested in patient cohorts at three different clinical scenarios between 2013 and 2019. Outpatients with indication for treatment with VKAs for at least 12 months were included. Patients were managed according to the criteria of the treating physician. Results: Patient general characteristics were similar between groups, except for the VKA indication. The results of 4,148 patients and 38,548 INR assessments were analyzed. The times in therapeutic range during the three phases of the study and pooled data were significantly higher for the anticoagulation clinic. Only the number of patient visits was significantly associated with the results, unlike age, gender, and type of VKA. Conclusions: VKAs are widely used, but it is difficult for therapeutic goals to be achieved, especially in non-specialized clinical services. Creation of anticoagulation clinics is an urgent need for the Mexican health system.

Uso profiláctico de la vitamina K para prevenir la enfermedad hemorrágica del recién nacido / Prophylactic use of vitamin K to prevent hemorrhagic disease of the newborn

El déficit de vitamina K al nacimiento supone un factor de riesgo para desarrollar la enfermedad hemorrágica del recién nacido (EHRN). Este estado pro hemorrágico puede producir sangrados graves principalmente a nivel cutáneo, gastrointestinal y cerebral. Hay buena evidencia de que la administración de vitamina K en el recién nacido (RN) es segura y eficaz, los daños potenciales son leves, por lo que está claro el beneficio neto a favor de la administración. El grupo PrevInfad recomienda administrar a todos los recién nacidos 1 mg de vitamina K de forma profiláctica por vía intramuscular para prevenir la EHRN. En el documento, se hacen consideraciones especiales para prematuros y para niños cuyos padres rechazan la profilaxis intramuscular. Asimismo, se presenta una propuesta operativa e información para padres (AU)

Vitamin K deficiency at birth is a risk factor for Haemorrhagic disease of the newborn. This bleeding prone situation can produce severe hemorrhages mainly in the skin, gastrointestinal tract and brain.There is strong evidence that the administration of vitamin K to the newborn is safe and effective, potential side effects are mild, so there is a clear benefit of its administration.PrevInfad workgroup recommends the prophylactic administration of 1 mg intramuscular Vitamin K to prevent the Haemorrhagic disease of the newborn.Some special considerations for preterm newborns and for children whose parents reject intramuscular prophylaxis are explained in the document. Moreover, an operative proposal and information for parents are presented. (AU)

Mortality in a cohort of primary care patients treated with vitamin K antagonist anticoagulants. / Mortalidad en una cohorte de pacientes de Atención Primaria tratados con anticoagulantes antagonistas de la vitamina K.

INTRODUCTION AND OBJECTIVES: The use of anticoagulants to prevent embolic events in Spain is very high, tending to a progressive increase. For this reason, we intend to analyse the mortality of patients from a metropolitan area of Granada treated with vitamin K antagonist anticoagulants (VKA), over 2 non-consecutive years. PATIENTS AND METHODS: Longitudinal, observational, retrospective study of 205 patients treated with VKA. Sociodemographic data, previous clinical conditions, pathology causing VKA treatment, degree of control and mortality were collected 2 years after the start of the study. RESULTS: Average age, 76±11.8 years (57.56% women). Two-year mortality was 22.4%, with a significant increase depending on age (p<.001) and years of treatment (p<.001). Patients with dementia (p<.05), with chronic kidney disease (p<.01) or with chronic obstructive pulmonary disease (p<.01) also presented higher mortality. Multivariate analysis showed significant effect of chronic kidney disease (odds ratio=4.075), chronic obstructive pulmonary disease (odds ratio=3.694), and years of treatment (odds ratio=1.236). CONCLUSIONS: At 2 years of follow-up, 1 in 5 patients treated with VKA died. The presence of chronic kidney disease, chronic obstructive pulmonary disease and a longer treatment time were independently associated with this increase of mortality. Most of the patients were anticoagulated by atrial fibrillation, they were elderly and had a high prevalence of comorbidities.

Oral anticoagulation in chronic kidney disease with atrial fibrillation.

Chronic kidney disease (CKD) and atrial fibrillation (AF) frequently coexist, amplifying the risk of cardiovascular events and mortality. In patients with CKD stage 3 and non-valvular AF, direct oral anticoagulants (DOACs) have shown, compared to vitamin K antagonists (VKA), equal or greater efficacy in the prevention of stroke and systemic embolism, and greater safety. There are no randomizedtrials of the efficacy and safety of DOACs and VKA in advanced CKD. On the other hand, observational studies suggest that DOACs, compared to warfarin, are associated with a lower risk of acute kidney damage and generation/progression of CKD. This paper reviews the epidemiological and pathophysiological aspects of the CKD and AF association, the evidence of the efficacy and safety of warfarin and ACODs in various stages of CKD with AF as well as the comparison between warfarin and ACODs in efficacy and anticoagulant safety, and in its renal effects.