Oral anticoagulant treatment in atrial fibrillation: the AFIRMA real-world study using natural language processing and machine learning.

INTRODUCTION: Oral anticoagulation (OAC) is key in atrial fibrillation (AF) thromboprophylaxis, but Spain lacks substantial real-world evidence. We aimed to analyze the prevalence, clinical characteristics, and treatment patterns among patients with AF undertaking OAC, using natural language processing (NLP) and machine learning (ML). MATERIALS AND METHODS: This retrospective study included AF patients on OAC from 15 Spanish hospitals (2014-2020). Using EHRead® (including NLP and ML), and SNOMED_CT, we extracted and analyzed patient demographics, comorbidities, and OAC treatment from electronic health records. AF prevalence was estimated, and a descriptive analysis was conducted. RESULTS: Among 4,664,224 patients in our cohort, AF prevalence ranged from 1.9% to 2.9%. A total of 57,190 patients on OAC therapy were included, 80.7% receiving Vitamin K antagonists (VKA) and 19.3% Direct-acting OAC (DOAC). The median age was 78 and 76 years respectively, with males constituting 53% of the cohort. Comorbidities like hypertension (76.3%), diabetes (48.0%), heart failure (42.2%), and renal disease (18.7%) were common, and more frequent in VKA users. Over 50% had a high CHA2DS2-VASc score. The most frequent treatment switch was from DOAC to acenocoumarol (58.6% to 70.2%). In switches from VKA to DOAC, apixaban was the most chosen (35.2%). CONCLUSIONS: Utilizing NLP and ML to extract RWD, we established the most comprehensive Spanish cohort of AF patients with OAC to date. Analysis revealed a high AF prevalence, patient complexity, and a marked VKA preference over DOAC. Importantly, in VKA to DOAC transitions, apixaban was the favored option.

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)

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)

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.

[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)

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)

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).

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.

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 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.

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. / Anticoagulación oral en la enfermedad renal crónica con fibrilación auricular.

Chronic kidney disease (CKD) and atrial fibrillation (AF) frequently coexist, amplifying the risk of cardiovascular events and mortality. In patients with CKD stage3 and non-valvular AF, direct oral anticoagulants (DOACs) have shown, compared to vitaminK antagonists (VKA), equal or greater efficacy in the prevention of stroke and systemic embolism, and greater safety. There are no randomized trials 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.

Cost and burden of poor anticoagulation control with vitamin K antagonists in patients with nonvalvular atrial fibrillation in Spain.

INTRODUCTION AND OBJECTIVES: The aim of this analysis was to evaluate the burden and cost of complications due to poor anticoagulation control in patients with nonvalvular atrial fibrillation (NVAF) treated with vitamin K antagonists (VKA) in Spain. METHODS: An analytical model was used to estimate annual differences in ischemic stroke, major bleeding, deaths, costs, and potential years of life lost between patients with poor anticoagulation control (time in therapeutic range <65%) and adequate control (time in therapeutic range ≥ 65%) with a 1-year time horizon. Information on the target population (patients ≥ 65 years), event rates, and costs were obtained from national sources. Direct costs in euros (2018) were included from the perspective of the national health system (NHS) and direct and indirect costs from the societal perspective. A sensitivity analysis was performed with post-hoc data from the SPORTIF III/V trials. RESULTS: We analyzed a hypothetical cohort of 594 855 patients, 48.3% with poor anticoagulation control, with an increase of 2321 ischemic strokes, 2236 major bleeding events and 14 463 deaths, and an annual incremental cost between €29 578 306 from the NHS perspective and €75 737 451 from the societal perspective. The annual impact of mortality was 170 502 potential years of life lost. The results of the sensitivity analysis showed that the annual cost would reach €97 787 873 from the societal perspective. CONCLUSIONS: Poor anticoagulation control with AVK has a strong impact on loss of health and on increased spending for the NHS.

Consenso argentino en gestión efectiva de clínicas de anticoagulación para uso de antagonistas de la vitamina K / Argentine consensus in effective management of anticoagulation clinics for the use of vitamin K antagonists

Resumen El tratamiento de un paciente anticoagulado con antagonistas de la vitamina K (AVK) sigue siendo un desafío, especialmente en regiones donde, por el costo, los dicumarínicos son todavía la alternativa más buscada a la hora de elegir un anticoagulante oral. Las clínicas de anticoagulación han demostrado ser la forma más eficiente y segura de evitar complicaciones trombóticas y hemorrágicas y de mantener al paciente en rango óptimo de tratamiento. Sin embargo, requieren de una adecuada infraestructura y personal capacitado para que funcionen eficientemente. En este consenso argentino se propone una serie de parámetros para la gestión efectiva de una clínica de anticoagulación. El objetivo es lograr una elevada calidad desde el punto de vista clínico-asistencial a través de un laboratorio de hemostasia de excelencia. Los criterios desarrollados en el documento fueron consensuados por un amplio grupo de expertos especialistas en hematología y en bioquímica de todo el país. Estos criterios deben adaptarse a la irregular disponibilidad de recursos de cada centro, pero siempre se los debe tener en cuenta a la hora de indicar el tratamiento anticoagulante con estas drogas. Tener en consideración estas premisas nos permitirá optimizar la atención del enfermo anticoagulado con AVK y de esta forma minimizar las intercurrencias trombóticas y hemorrágicas a las que está expuesto, para así honrar nuestra promesa de no dañar al paciente.

Abstract Treating an anticoagulated patient with vitamin K antagonists (VKA) remains a challenge, especially in areas where dicoumarins are still the first drug of choice due to the cost of other oral anticoagulants. Anticoagulation clinics have proven to be the most efficient and safe way to avoid thrombotic and hemorrhagic complications and to keep patients in optimal treatment range. However, they require adequate infrastructure and trained personnel to work properly. In this Argentine consensus we propose a series of guidelines for the effective management of the anticoagulation clinics. The goal is to achieve the excellence in both the clinical healthcare and the hemostasis laboratory for the anticoagulated patient. The criteria developed in the document were agreed upon by a large group of expert specialists in hematology and biochemistry from all over the country. The criteria presented here must always be considered when indicating VKA although they had to be adapted to the unequal reality of each center. Taking these premises into consideration will allow us to optimize the management of the anticoagulated patient with VKA and thus minimize thrombotic and hemorrhagic intercurrences, in order to honor our promise not to harm the patient.

[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-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.