Predictors of Hospitalization in Vitamin K Antagonist Users Presenting with Bleeding at the Emergency Department

Abstract Background Vitamin K antagonists (VKA) are indicated for the prevention of thromboembolic events and reduction of mortality in patients with atrial fibrillation and patients with valvular prostheses. However, their use is associated with bleeding complications and hospitalizations. Predictors of hospital admission for bleeding in these patients are poorly known. Objectives To define the predictors for hospitalization of VKA users who seek emergency care due to bleeding. Methods Single-center, cross-sectional study, with retrospective analysis of electronic medical records from 03/01/2012 to 02/27/2017. Clinical and laboratory variables were compared between patients who were hospitalized and those who were not. A logistic regression model as used, in which the variables were included using the Backward stepwise method, with a p value of 0.05 as the input criterion, a removal value of 0.20 and a confidence interval of 95%. The p-value was considered statistically significant when <0.05. Results A total of 510 patients with bleeding were included, of whom 158 were hospitalized. Predictors of hospitalization were: INR at supratherapeutic levels (OR 3.45; P <0.01; 95% CI 1.58 - 7.51), gastrointestinal bleeding (OR 2.36; P <0.01; CI 95% 1.24 - 4.50), drop in hemoglobin (OR 6.93; P <0.01; 95% CI 3.67 - 13.07), heart failure (OR 1.96; P 0.01; 95% CI 1.16 - 3.30) and need for blood transfusion (OR 8.03; P <0.01; 95% CI 2.98 - 21.64). Conclusion Drop in hemoglobin, heart failure, INR at supratherapeutic levels, gastrointestinal bleeding and need for blood transfusion were associated with hospitalization. Identification of these factors in the initial evaluation would help to define which patients will demand more intensive care.

Riesgo de sangrado en pacientes anticoagulados con antagonistas de la vitamina K que reciben antibióticos / Risk of bleeding in anticoagulated patients with vitamin K antagonists who receive antibiotics

Lograr un adecuado nivel de anticoagulación con antagonistas orales de la vitamina K suele ser un desafío frecuente en la práctica clínica, dado que su estrecho rango terapéutico suele verse afectado por diversas interacciones farmacológicas,alimentos y condiciones clínicas. A partir de un caso de un paciente anticoagulado que presenta una hemorragia gastro-intestinal posterior a realizar un tratamiento antibiótico, la autora de este artículo revisó la evidencia sobre el riesgo desangrado secundario a la interacción entre este tipo de anticoagulantes y antibióticos orales. Su conclusión tras realizar una búsqueda bibliográfica y seleccionar la mejor evidencia disponible, es que existe un aumento del riesgo relativo desangrado en pacientes anticoagulados que reciben antibióticos, por lo que deberían evitarse aquellos antibióticos con conocido potencial de interacción. Si ello no fuera posible, se recomienda monitorizar el estado de anticoagulación con dosaje de la razón internacional normatizada (RIN) posterior a la introducción del antibiótico. (AU)

Achieving an adequate level of anticoagulation with oral vitamin K antagonists is often a frequent challenge in clinical practice, given that their narrow therapeutic range is often affected by various drug interactions, food, and clinical conditions. Based on a case of an anticoagulated patient who presented gastrointestinal bleeding after antibiotic treatment, the authorof this article reviewed the evidence on the risk of secondary bleeding due to the interaction between this type of anticoagulants and oral antibiotics. Their conclusion, after performing a literature search and selecting the best available evidence, is that there is an increased relative risk of bleeding in anticoagulated patients receiving antibiotics, so antibiotics with known potential for interaction should be avoided. If it weren't possible, it is recommended to monitor the anticoagulation status with International Normalized Ratio (INR) dosing after the introduction of the antibiotic. (AU)

Mortalidad y hospitalización en una consulta de anticoagulación y trombosis: Experiencia del Centro Cardiovascular Regional Ascardio / Mortality and hospitalization of an anticoagulation and thrombosis consult experience from the Centro Cardiovascular Regional Ascardio

El tratamiento anticoagulante oral con fármacos inhibidores de la vitamina K como la warfarina se viene utilizando desde hace décadas para la terapia y prevención de la enfermedad tromboembólica con efectos secundarios ampliamente conocidos, pero con una utilidad clínica bien contrastada. El objetivo de este estudio fue determinar la proporción de mortalidad y hospitalización de la consulta de anticoagulación y trombosis del Centro Cardiovascular Regional ASCARDIO en el año 2017 para lo cual se realizó un estudio descriptivo transversal que incluyó una muestra de 294 pacientes. La principal indicación de anticoagulación fue la fibrilación auricular (73%) seguida de la enfermedad tromboembólica venosa (13%) e isquemia miocárdica (9%). Se registró una mortalidad de 11,7% siendo la principal causa de muerte de origen cardíaco (58%). La edad promedio de los pacientes fallecidos fue de 65 años, siendo 53% del sexo femenino; para el momento de la muerte, el 65% de los pacientes estaba tomando warfarina. La hospitalización se observó en el 10% de la muestra siendo la principal causa de la misma la cardíaca (60%) seguida de causas hemorrágicas (18%); de los pacientes hospitalizados, la edad promedio fue de 66 años siendo 52% del sexo femenino; el 90% de los pacientes estaba tomando warfarina al momento de la hospitalización. El análisis de riesgo para mortalidad y hospitalización según causa y estatus de warfarina no mostró significancia estadística. No se evidenció relación de riesgo estadísticamente significativa entre muerte, hospitalización y estatus de la warfarina. Hubo mayor proporción de muertes (45%) y hospitalización (17%) en el grupo que ingresó con diagnóstico de isquemia miocárdica(AU)

Oral anticoagulant treatment with vitamin K inhibitor drugs such as warfarin has been used for decades for the therapy and prevention of thromboembolic disease with widely known side effects but with well-proven clinical utility. To determine the proportion of mortality and hospitalization of the anticoagulation and thrombosis clinic of the ASCARDIO Regional Cardiovascular Center in 2017 a descriptive cross-sectional study was carried out that included a sample of 294 patients. The results show that the main indication for anticoagulation was atrial fibrillation (73%) followed by venous thromboembolic disease (13%) and myocardial ischemia (9%). An 11.7% mortality rate was observed. The mean age of the deceased was 65 years with a slight prevalence of the female sex (53%). The main cause of death was cardiac (58%) and 65% of the deceased patients were taking warfarin at the moment of death. A 10% hospitalization rate was observed with an average age of hospitalized patients of 66 years; 52% were females. The main cause of hospitalization was cardiac (60%) followed by hemorrhage (18%) and 90% of the patients were taking warfarin at the time of hospitalization. The risk analysis for mortality and hospitalization according to cause and status of warfarin did not show statistical significance. There was a higher proportion of deaths (45%) and hospitalization (17%) in the group admitted with a diagnosis of myocardial ischemia(AU)

Farmacogenómica de los anticoagulantes orales: la importancia de establecer algoritmos de dosificación en población chilena

There is an important interindividual variability in dose requirement for coumarinic anticoagulants, which could be explained by genetic and non-genetic factors. Among hereditary factors, there are gene polymorphisms that code the therapeutic target and the main enzyme responsible for their metabolism. However, there are other candidate genes that could modulate dose requirements. The is a paucity of pharmacogenomic platforms to determine dose requirements of coumarinics in the Chilean population. Therefore, algorithms considering different variables to adjust individual dosages are required. Herein, we analyze the available evidence about factors that can modify the effects of vitamin K antagonists and that should be incorporated to dosing algorithms.

Eficacia en el control de la anticoagulación de los diferentes fármacos antagonistas de la vitamina K disponibles en Chile

Background: Vitamin K antagonist medications (VKA) are essential for the prevention of thromboembolic events, but their effectiveness is influenced by multiple factors, such as the type of medication chosen. Aim: To evaluate the efficacy in anticoagulant control of the bioequivalent and non-bioequivalent drugs of acenocoumarol compared to the reference drug. To evaluate the efficacy of warfarin bioequivalents available in Chile. To contrast the overall anticoagulant control efficacy between acenocoumarol and warfarin. Material and Methods: The results of 69333 outpatient oral anticoagulation controls were analyzed. Patient were separated in groups according to the drug that they used. Subsequently, the proportions of controls outside the range for each of acenocoumarol and warfarin bioequivalent drugs were compared. Acenocoumarol non-bioequivalent drugs were also compared with the reference drug. Acenocoumarol was compared with warfarin. Results: Acenocoumarol bioequivalent drugs and the reference drug had a similar proportion of controls outside the range (Odds ratios (OR) 0.812; 0.969; 0.974 and 0.963). Non-bioequivalent drugs had a higher proportion than the reference drug (OR 1.561 and 2.037). Both warfarin brands have a similar proportion of controls outside of the range (OR 1.050). Acenocoumarol compared to warfarin had a significant higher proportion of controls outside the range (OR 1.191). Conclusions: The pharmacological presentation of vitamin K antagonists could influence anticoagulant control. Therefore, it is not prudent to switch these presentations frequently.

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.

Warfarin drug interaction with vitamin K and other foodstuffs / Interacción de la droga warfarina con la vitamina K y otros productos alimenticios

Vitamin K is found in higher concentrations in dark green plant and in vegetable oils. The adequate intake of vitamin K is 90 and 120ug/day for adult elderly men and women, respectively. The main function of vitamin K is to act as an enzymatic cofactor for hepatic prothrombin synthesis, blood coagulation factors, and anticoagulant proteins. Prominent among the many available anticoagulants is warfarin, an antagonist of vitamin K, which exerts its anticoagulant effects by inhibiting the synthesis of vitamin K1 and vitamin KH2. From the beginning of the therapy it is necessary that the patients carry out the monitoring through the prothrombin time and the international normalized ratio. However, it is known that very low intake and/or fluctuations in vitamin K intake are as harmful as high consumption. In addition, other foods can interact with warfarin, despite their content of vitamin K. The aim of this study was to gather information on the drug interaction of warfarin with vitamin K and with dietary supplements and other foods.

La vitamina K se encuentra en concentraciones más altas en plantas de color verde oscuro y en aceites vegetales. La ingesta adecuada de vitamina K es de 90 y 120 ug/día para hombres y mujeres adultos mayores, respectivamente. La función principal de la vitamina K es actuar como un cofactor enzimático para la síntesis de protrombina hepática, factores de coagulación de la sangre y proteínas anticoagulantes. Entre los muchos anticoagulantes disponibles destaca la warfarina, un antagonista de la vitamina K, que ejerce sus efectos anticoagulantes al inhibir la síntesis de la vitamina K1 y la vitamina KH2. Desde el inicio de la terapia, es necesario que los pacientes realicen el monitoreo a través del tiempo de protrombina y la proporción normalizada internacional. Sin embargo, se sabe que una ingesta muy baja y/o fluctuaciones en la ingesta de vitamina K son tan dañinas como un consumo alto. Además, otros alimentos pueden interactuar con la warfarina, a pesar de su contenido de vitamina K. El objetivo de este estudio fue recopilar información sobre la interacción de los medicamentos de la warfarina con la vitamina K y con los suplementos dietéticos y otros alimentos.

Trends and Predictors of Oral Anticoagulation in Patients with Atrial Fibrillation: A Serial Cross-Sectional Study from 2011 to 2016

Abstract Background: Despite the efficacy of vitamin K antagonists against stroke in patients with atrial fibrillation (AF), the underuse of this therapy is well documented. Objectives: To evaluate trends and predictors of oral anticoagulants utilization in patients with AF. Methods: Observational, retrospective, serial cross-sectional study between 2011-2016. Comparisons between groups were performed using the Student t, Mann-Whitney and Chi-square tests. Logistic regression was used to identify independent predictors of anticoagulation. A p value < 0.05 was considered significant. Results: A total of 377 patients were analyzed. The mean age was 70 ± 15 years; 52% were male and 75% were anticoagulated (20% with VKA and 55% with DOAC). Over 5 years, the overall frequency of anticoagulation increased by 22.4%. The use of DOACs increased from 29% to 70%, whereas the use of VKA decreased from 36% to 17%. The use of antiplatelet agents alone also fell from 21% to 6%. The predictors of anticoagulation were previous episodes of AF (OR 3.1, p < 0.001), hypertension (OR 3.0, p < 0.001) and HASBLED score (OR 0.5, p < 0.001). The predictors of DOAC use were serum creatinine (OR 0.2, p = 0.002), left atrial size (OR 0.9, p = 0.003) and biological valve prosthesis (OR 0.1, p = 0.007). Of the 208 patients using DOACs, 63 (30%) received inadequate prescriptions: 5 with severe drug interactions and 58 with incorrect dosing. Conclusions: Between 2011 and 2016, DOACs were rapidly incorporated into clinical practice, replacing AVKs and antiplatelets, and contributing to greater use of anticoagulation in patients with AF.

Pacientes con fibrilación auricular no valvular tratados con antivitamina K o anticoagulantes directos: perfil de paciente y efectos a largo plazo / Patients with non-valvular atrial fibrillation on vitamin k antagonists or direct-acting oral anticoagulants: patients profile and long-term follow up outcomes

Resumen Introducción: La llegada de los anticoagulantes directos (ACD) ha supuesto un cambio en el tratamiento de la fibrilación auricular no valvular (FANV) en los últimos años. Los objetivos de este estudio son determinar el grado de control de la anticoagulación con antivitamina K (AVK) y su posible implicación en efectos cardiovasculares adversos mayores (ECAM) y evaluar las diferencias entre el grupo en tratamiento con AVK respecto del grupo con ACD. Pacientes y métodos: Estudio de cohorte prospectivo que incluyó a pacientes consecutivos diagnosticados con FANV valorados en el Servicio de Cardiología con un seguimiento de 18 meses. Se analizaron diferencias demográficas, clínicas y analíticas entre grupos, incluido el grado de control de la anticoagulación del grupo AVK y su posible relación con ECAM. Resultados: Se incluyó a 273 pacientes: 46.5% tratados con AVK, 42.5% con ACD y 11% sin tratamiento anticoagulante. El control de la anticoagulación con AVK fue del 62.1%, sin diferencias en ECAM en función de control. El grupo ACD presentó menos ECAM que el grupo de AVK (13.4 vs. 4.3%; HR, 0.90; 0.83-0.98; p = 0.01), con una menor mortalidad cardiovascular (0.0 vs. 5.5%; HR, 0.94; 0.90-0.98; p = 0.01) y total (0.9 vs. 12.6%; HR, 0.88; 0.82-0.94; p menor que 0,01), aunque sin diferencias significativas en eventos hemorrágicos (0.9 vs. 4.7%; p = 0.07) ni isquémicos (2.6 vs. 0.8%; p = 0.27). Discusión: Los pacientes con AVK poseen un perfil clínico diferente en comparación con los que reciben ACD. El control de anticoagulación del grupo de AVK fue inadecuado en casi la mitad de los casos. El grupo de AVK presentó más ECAM que el grupo de ACD.

Abstract Introduction: The arrival of direct-acting oral anticoagulants (DOACs) has led to a change in the management of non-valvular atrial fibrillation (NVAF) in recent years. The objectives of this study are to determine the level of therapeutic control of anticoagulation with vitamin K antagonists (VKA) and its possible involvement in major adverse cardiovascular events (MACE) and to evaluate differences between the group on VKA with respect to the group on DOACs. Patients and methods: Prospective cohort study that included consecutive patients diagnosed with NVAF in Cardiology Consultations with a clinical follow-up of 18 months. Demographic, clinical and analytical differences between groups were analyzed, including the level of therapeutic control of anticoagulation on the VKA group and its association with MACE. Results: Overall, 273 patients were included: 46.5% on VKA, 42.5% on DOACs, 11% without antithrombotic treatment. Patients on VKA spent 62.1% of their time within therapeutic range (TTR by the Rosendaal formule). There were no differences in MACE depending on anticoagulation control. The DOACs group presented lesser MACE rate than the VKA group (13.4 vs. 4.3%; 0.90; HR 0.90; 0.83-0.98 p = 0.01) with lower cardiovascular mortality (0.0 vs. 5.5%; HR, 0.94; 0.90-0.98; p = 0.01) and total mortality (0.9 vs. 12.6%; HR, 0.88; 0.82-0.94; p less 0.01) although without significant differences in hemorrhagic (0.9 vs. 4.7 %; p = 0.07), or ischemic events (2.6 vs. 0.8%, p = 0.27). Conclusions: Patients on VKA have a different clinical profile than those who receive DOACs. Patients on VKA have an inadequate control of the anticoagulation in quite the half of the cases. The VKA group presented more MACE than the DOACs group.

Factores relacionados con el efecto de fármacos antagonistas de la vitamina K / Fatores relacionados ao efeito de drogas antagonistas da vitamina K / Factors related to the effect of vitamin K antagonist drugs

Introducción: la prescripción de fármacos inhibidores de la vitamina K exige el control del efecto anticoagulante. Objetivo: caracterizar a los pacientes con antecedentes de tratamiento con warfarina sódica al momento del ingreso en la unidad de terapia intensiva del Hospital General Docente Dr Agostinho Neto durante el periodo 2016- 2018. Método: se realizó estudio analítico, retrospectivo y longitudinal. Se estudiaron 54 pacientes con las características señaladas, que se agruparon en un grupo control (n=16) con anticoagulación adecuada y un grupo estudio (n=38) también con anticoagulación adecuada. Se estudiaron variables sociodemográficas, clínicas y de laboratorio. Resultados: Un total de 16 pacientes presentó nivel adecuado de anticoagulación y en, 38, nivel de anticoagulación fue inadecuado. La warfarina sódica se indicó más en pacientes con prótesis valvular cardiaca mecánica (20,0 por ciento), y en estos fue más común la anticoagulación inadecuada. Los factores más relacionados con la anticoagulación adecuada fueron la supervisión médica frecuente (p=0,0000), que no usaron fármacos que interfieran con la acción del fármaco (p=0,0000) y el cumplimiento del tratamiento (p=0,0000). En 22 pacientes se presentaron complicaciones hemorrágicas y la más común fue la hemorragia cerebral y, 16, presentaron complicaciones tromboembólicas y la más frecuente fue el embolismo cerebral. Fallecieron 3 pacientes por complicaciones hemorrágicas y 9 por complicaciones tromboembólicas. En 21 pacientes la indicación del fármaco fue inapropiada. Conclusiones: se revela la necesidad del control de la adecuada adherencia terapéutica del paciente pues el inadecuado efecto anticoagulante genera complicaciones que pueden determinar la muerte del paciente(AU)

Introduction: the prescription of vitamin K inhibitor drugs requires control of the anticoagulant effect. Objective: to characterize patients with a history of treatment with warfarin sodium at the time of admission to the intensive care unit of the General Teaching Hospital Dr Agostinho Neto during the 2016-2018 period. Method: an analytical, retrospective and longitudinal study was carried out. 54 patients with the characteristics indicated were studied, which were grouped in a control group (n=16) with adequate anticoagulation and a study group (n=38) also with adequate anticoagulation. Sociodemographic, clinical and laboratory variables were studied. Results: A total of 16 patients presented adequate level of anticoagulation and, in 38, level of anticoagulation was inadequate. Sodium warfarin was indicated more in patients with mechanical cardiac valve prostheses (20.0per cent), and inadequate anticoagulation was more common in these. The factors most related to adequate anticoagulation were frequent medical supervision (p=0.0000), who did not use drugs that interfere with the action of the drug (p=0.0000) and treatment compliance (p=0.0000). In 22 patients there were hemorrhagic complications and the most common was cerebral hemorrhage and, 16, they presented thromboembolic complications and the most frequent was cerebral embolism. Three patients died from bleeding complications and 9 from thromboembolic complications. In 21 patients the indication of the drug was inappropriate. Conclusions: the need to control the adequate therapeutic adherence of the patient is revealed because the inadequate anticoagulant effect generates complications that can determine the death of the patient(AU)

Introdução: a prescrição de medicamentos inibidores da vitamina K requer controle do efeito anticoagulante. Objetivo: caracterizar pacientes com histórico de tratamento com varfarina sódica no momento da admissão na unidade de terapia intensiva do Hospital Geral de Ensino Dr Agostinho Neto no período 2016-2018.Método: estudo analítico, retrospectivo e longitudinal. Foram estudados 54 pacientes com as características indicadas, os quais foram agrupados em um grupo controle (n=16) com anticoagulação adequada e um grupo estudo (n=38) também com anticoagulação adequada. Foram estudadas variáveis sociodemográficas, clínicas e laboratoriais. Resultados: Um total de 16pacientes apresentou nível adequado de anticoagulação e, em 38, o nível de anticoagulação foi inadequado. A varfarina sódica foi mais indicada em pacientes com próteses valvares cardíacas mecânicas (20,0 por cento), sendo a anticoagulação inadequada mais comum. Os fatores mais relacionados à anticoagulação adequada foram a supervisão médica frequente (p=0,0000), que não utilizou medicamentos que interferem na ação do medicamento (p=0,0000) e adesão ao tratamento (p=0,0000) Em 22 pacientes houve complicações hemorrágicas e a mais comum foi hemorragia cerebral; 16 apresentaram complicações tromboembólicas e a mais frequente foi embolia cerebral. Três pacientes morreram por complicações hemorrágicas e 9 por complicações tromboembólicas. Em 21 pacientes, a indicação do medicamento foi inadequada. Conclusões: a necessidade de controlar a aderência terapêutica adequada do paciente é revelada, pois o efeito anticoagulante inadequado gera complicações que podem determinar a morte do paciente(AU)

Uninterrupted Use of Oral Anticoagulants for the Ablation of Atrial Flutter: A Single Center Cohort of 154 Patients / Uso Ininterrupto de Anticoagulantes Orais na Ablação de Flutter Atrial Istmo-Cavotricuspídeo Dependente: Coorte Unicêntrica de 154 Pacientes

Abstract Background: The uninterrupted use of oral anticoagulation (OAC) with vitamin K antagonists (VKAs) for electrophysiology procedures has been more and more recommended. The clinical practice in our service recommends the continuous use of these drugs for atrial flutter ablation. There is little evidence as to the uninterrupted use of non-vitamin K antagonist oral anticoagulants (NOACs) in this scenario. Objective: To compare the rates of complications related with the uninterrupted use of different types of oral anticoagulants in patients referred to atrial flutter (AFL) ablation. Methods: Historical, single-center cohort of ablation procedures by AFL conducted from November 2012 to April 2016. The primary outcome was the occurrence of hemorrhagic or embolic complication during the procedure. The secondary outcome was the occurrence of stroke or transient ischemic attack (TIA) in follow-up. The statistical significance level was 5%. Results: There were 288 ablations per AFL; 154 were carried out with the uninterrupted use of OAC (57.8% with VKA and 42.2% with NOAC). Mean age was 57 ± 13 years. The rate of hemorrhagic complication during the procedure was 3% in each group (p = NS). The rate of stroke/TIA was, respectively, of 56/1,000 people-year in the VKA group against zero/1,000 people-year in the NOAC group (p = 0.02). Conclusion: In our population there were no hemorrhagic complications regarding the procedure of OAC use uninterruptedly, including NOACs. There was higher occurrence of stroke/TIA in the follow-up of the group of patients undergoing VKAs; however, this difference may not only be a result of the type of OAC used.

Resumo Fundamento: O uso ininterrupto de anticoagulação oral (ACO) com antagonistas da vitamina K (AVKs) para procedimentos de eletrofisiologia está sendo cada vez mais recomendado. A prática clínica em nosso serviço é de uso continuado dessas drogas para ablação de flutter atrial. Existem poucas evidências quanto ao uso ininterrupto dos anticoagulantes orais não antagonistas da vitamina K (NOACs) nesse cenário. Objetivos: Comparar as taxas de complicações relacionadas ao uso ininterrupto de diferentes tipos de anticoagulantes orais em pacientes referidos para ablação por flutter atrial (FLA). Métodos: Coorte histórica e unicêntrica dos procedimentos de ablação por FLA realizados no período de novembro de 2012 a abril de 2016. O desfecho primário foi o de ocorrência de complicação hemorrágica ou embólica durante o procedimento. O desfecho secundário foi o de ocorrência de acidente vascular cerebral (AVC) ou acidente isquêmico transitório (AIT) no acompanhamento. O nível de significância estatística adotado foi de 5%. Resultados: Foram incluídas 288 ablações por FLA; 154 foram feitas com uso ininterrupto de ACO (57,8% com AVK e 42,2% com NOAC). A idade média foi de 57 ± 13 anos. A taxa de complicação hemorrágica durante o procedimento foi de 3% em cada grupo (p = NS). A taxa de AVC/AIT foi, respectivamente, de 56/1.000-pessoas-ano no grupo AVK contra zero/1.000-pessoas-ano no grupo NOAC (p = 0,02). Conclusão: Em nossa população não ocorreram complicações hemorrágicas relacionadas ao procedimento com uso de ACO de forma ininterrupta, incluindo NOACs. Houve maior ocorrência de AVC/AIT no seguimento no grupo de pacientes em uso de AVK, contudo essa diferença pode não ser decorrente apenas do tipo de ACO em uso.

Evaluación de la estrategia de terapia antitrombótica posterior al cambio valvular aórtico con válvulas biológicas en pacientes de bajo riesgo trombótico / Evaluation of the antithrombotic strategy in low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis

Resumen De acuerdo a las guías actuales, aún es materia de debate el uso de anticoagulación en los primeros 3 meses en pacientes de bajo riesgo trombótico sometidos a cambio valvular aórtico con prótesis biológicas. En base a la evidencia actual, la aspirina a dosis bajas es razonable como alternativa a los antagonistas de la vitamina K (AVK) durante el posquirúrgico temprano en pacientes con prótesis biológicas en posición aórtica. Se comparó la incidencia de complicaciones trombóticas o hemorrágicas de acuerdo a la estrategia de terapia antitrombótica en los pacientes de bajo riesgo trombótico sometidos a cambio valvular aórtico con válvulas biológicas en el Instituto Nacional de Cardiología Ignacio Chávez. La hipótesis: la aspirina como monoterapia antitrombótica tiene un efecto benéfico comparado con los AVK. Se estudiaron los pacientes de bajo riesgo trombótico sometidos a cambio valvular aórtico con válvulas biológicas en el Instituto Nacional de Cardiología Ignacio Chávez. Se incluyeron los pacientes operados del año 2011 al 2015. Se identificó en el seguimiento a un año la presencia de complicaciones trombóticas o hemorrágicas y si se manejaron con cualquiera de las siguientes: aspirina únicamente, AVK solo y la combinación aspirina más AVK. Se analizaron 231 pacientes. Solo se presentó una complicación hemorrágica en un paciente tratado con AVK. No hubo complicaciones trombóticas. No se presentaron complicaciones trombóticas en pacientes que no recibieron anticoagulación oral formal durante los primeros 3 meses posquirúrgicos, lo que indica que es seguro el uso de aspirina como monoterapia en estos pacientes de bajo riesgo trombótico.

Abstract According to current guidelines, in patients without additional risk factors who have undergone aortic valve replacement with a bioprosthesis, anticoagulation in the first 3 months after surgery is still a matter of debate. According to current evidence, aspirin in low doses is a reasonable alternative to vitamin K antagonists (VKA). A comparison is made between the incidence of thrombotic and haemorrhagic complications in patients with low thrombotic risk who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico. The hypothesis: aspirin as monotherapy has a beneficial effect compared to VKA. The studied patients were the low thrombotic risk patients who underwent aortic valve replacement with a bioprosthesis in the National Institute of Cardiology of Ignacio Chávez of Mexico from 2011 to 2015. The groups studied were: aspirin only, VKA only, and the combination of VKA plus aspirin. The patients were retrospectively followed-up for 12 months, and the thrombotic and haemorrhagic complications were documented. Of the 231 patients included in the study, only one patient in the VKA only group presented with a haemorrhagic complication. No thrombotic complications were observed. In the present study no thrombotic complications were observed in patients who did not receive anticoagulation in the first 3 months after an aortic valve replacement with a bioprosthesis after a follow up period of 12 months. This suggests that the use of aspirin only is safe during this period.

Índice predictivo de la anticoagulación con antagonistas de la vitamina K / Predictive index of the anticoagulant with antagonists of the vitamin K

Introducción: se recomienda la predicción del riesgo de sangrado durante la anticoagulación terapéutica. Objetivo: diseñar un modelo predictivo del control de la anticoagulación en pacientes tratados con warfarina sódica. Método: se realizó un estudio explicativo y prospectivo en 50 pacientes tratados con warfarina sódica en el Hospital General Docente Dr Agostinho Neto durante el período 2015-2016. Estos se agruparon en un grupo control (n=25, aquellos con adecuada anticoagulación, INR entre 2.0 - 3.0) y un grupo estudio (n=25, con inadecuada anticoagulación, INR < 2.0). Resultados: Los factores más predictivos del efecto anticoagulante insatisfactorio fueron: vivir solo y el uso de fármacos que interfieren con más constancia e intensidad en el efecto del fármaco. Conclusiones: se diseñó un modelo predictivo del control de la anticoagulación con warfarina, ajustado a los servicios del Hospital Dr Agostinho Neto(AU)

Introduction: it recommends the prediction of the risk of bleeding during the therapeutic anticoagulation. Aim: design a predictive model of the control of the anticoagulant in patients treated with warfarina sódica. Method: it realised an explanatory and prospective study in 50 patients treated with warfarina sódica in the Educational General Hospital "Dr. Agostinho Neto" during the period 2015-2016. These grouped in a group control (n=25, those with suitable anticoagulation, INR between 2.0-3.0) and a group study (n=25, with unsuitable anticoagulation, INR < 2.0). Results: The most predictive factors of the effect unsatisfactory anticoagulant were: live alone and the use of drugs that interfere with more proof and intensity in the effect of the drug. Conclusions: it designed a predictive model of the control of the anticoagulation with warfarina, adjusted to the services of the Hospital Dr Agostinho Neto(AU)

Manejo perioperatorio de pacientes con tratamiento anticoagulante crónico / Perioperative management of patients with chronic anticoagulant therapy

Resumen La terapia anticoagulante es ampliamente utilizada en la práctica clínica, como profilaxis en pacientes con riesgo de presentar fenómenos tromboembólicos o como tratamiento en aquellos que han presentado algún evento trombótico. Cada vez es más frecuente enfrentarse a pacientes en tratamiento anticoagulante crónico que serán intervenidos mediante procedimientos quirúrgicos, por lo que es importante y necesario conocer el manejo perioperatorio de los diferentes fármacos anticoagulantes, para disminuir los riesgos y complicaciones asociados a la suspensión o mantención de estos en el período perioperatorio. Para lograr este objetivo se debe evaluar y balancear el riesgo de sangrado versus el riesgo de eventos tromboembólicos, considerando la condición médica de cada paciente y el tipo de procedimiento quirúrgico que recibirá. La recomendación para fármacos anticoagulantes orales antagonistas de vitamina K es mantenerlos en cirugías con bajo riesgo de sangrado y suspenderlos 5 días antes de procedimientos quirúrgicos con riesgo hemorrágico moderado y alto, controlando el international normalized ratio el día previo a la cirugía. Los nuevos anticoagulantes orales no requieren monitorización de rutina, recomendándose suspenderlos a las 24-96 h previas al procedimiento quirúrgico, dependiendo del riesgo hemorrágico de cada cirugía y de la función renal. En relación con los anticoagulantes parenterales, la heparina no fraccionada en infusión intravenosa se recomienda suspenderla 4-5 h antes de la cirugía, mientras que la utilizada vía subcutánea, 12 h previas a la intervención quirúrgica. Las heparinas de bajo peso molecular en dosis de tratamiento se sugiere descontinuarlas 24 h previas a la cirugía, mientras que las usadas en dosis profilácticas, solo 12 h antes.

Anticoagulant therapy is widely used in clinical practice, as prophylaxis in patients at risk of presenting thromboembolic phenomena or as treatment in those who have presented a thrombotic event. It is increasingly the number of patients on chronic anticoagulant therapy to undergo surgical procedures, so it is important and necessary to know the perioperative management of the different anticoagulant drugs to reduce the risks and complications associated with suspension or maintenance of these in the perioperative period. To achieve this goal, the risk of bleeding should be evaluated and balanced against the risk of thromboembolic events, considering the medical condition of each patient and the type of surgical procedure to which they have undergone. The recommendation for vitamin K antagonist oral anticoagulant drugs is to maintain them for surgeries at low risk of bleeding and to suspend them 5 days before surgical procedures with moderate and high bleeding risk, controlling 'International Normalized Ratio' the day before surgery. The new oral anticoagulants do not require routine monitoring, recommending suspending them 24-96 h prior to the surgical procedure, depending on the hemorrhagic risk of each surgery and renal function of patient. In relation to parenteral anticoagulants, unfractionated heparin in intravenous infusion is recommended to be discontinued 4-5 h prior to surgery, while the subcutaneous route, 12 h prior to surgery. Low-molecular-weight heparins in treatment doses should be suspended 24 h prior to surgery, while in prophylactic doses, only 12 h earlier.

Use of direct oral anticoagulants for chronic thromboembolic pulmonary hypertension

OBJECTIVES: Chronic thromboembolic pulmonary hypertension is one of the most prevalent forms of pulmonary hypertension and is a major complication of acute pulmonary embolism. One mainstay of chronic thromboembolic pulmonary hypertension treatment is lifelong anticoagulation. The recent advent of direct oral anticoagulants for acute pulmonary embolism treatment has provided a viable and effective alternative for treating this condition. However, little is known about the efficacy of this new class of drugs for treating chronic thromboembolic pulmonary hypertension. We aimed to evaluate the safety and efficacy of direct oral anticoagulants in the treatment of chronic thromboembolic pulmonary hypertension. METHODS: A cohort of chronic thromboembolic pulmonary hypertension patients who initiated treatment with direct oral anticoagulants between June 2015 and November 2016 were enrolled in this study. RESULTS: Sixteen patients used rivaroxaban, three used dabigatran and one used apixaban for a mean follow-up of 20.9 months. The mean age was 51 years, and eighteen patients were classified as functional class II/III. Eight patients underwent a pulmonary endarterectomy and exhibited clinical, hemodynamic and functional improvement and currently continue to use direct oral anticoagulants. No episode of venous thromboembolism recurrence was identified during the follow-up period, but there was one episode of major bleeding after a traumatic fall. CONCLUSIONS: Although direct oral anticoagulants appear to be a safe and effective alternative for treating chronic thromboembolic pulmonary hypertension, larger studies are needed to support their routine use.

Características basales, manejo de terapias antitrombóticas y pronóstico de pacientes chilenos con FA no valvular. Lecciones del Registro GARFIELD AF en Chile / Features, management and prognosis of Chilean patients with non valvular atrial fibrillation: GARFIELD AF registry

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with high rates of death, ischemic stroke and systemic embolism (SE). There is scarce information about clinical characteristics and use of anti-thrombotic therapies in Chilean patients with non-valvular AF. Aim: To describe the characteristics and 1-year outcomes of patients with recently diagnosed AF recruited in Chile into the prospective global GARFIELD-AF registry. Material and Methods: Between 2011-2016, we prospectively registered information of 971 patients recruited at 15 centers, 85% of them from the public system and 15% from the private sector. Demographics, clinical characteristics and use of antithrombotic therapies were recorded for all patients. Adverse clinical outcomes were analyzed in 711 patients with 1-year follow-up. Results: The mean age was 71.5 years (66-79), 50% were men. Mean CHAD2S2 Vasc and HAS BLED scores for stroke risk were 3.3 (2.0-4.0) and 1.5 (1.0-2.0) respectively. Oral anticoagulants were prescribed in 82% of patients. Seventy percent received Vitamin K antagonists, 10% novel direct anticoagulants or antiplatelet therapy and only 8% did not receive any antithrombotic therapy. Mean time in optimal therapeutic range (an international normalized ratio of 2 to 3), was achieved in only 40.7% (23.0-54.8) of patients receiving Vitamin K antagonists. One year rates of death, stroke/systemic embolism and bleeding were 4.75 (3.36-6.71), 2.40 (1.47-3.92) and 1.64% (0.91-2.97) per 100 person-years. Ischemic stroke occurred in 1.8% and hemorrhagic stroke in 0.8% of patients at 1-year of follow up. Conclusions: Although the use of vitamin K antagonists at baseline was high, the mean time in optimal therapeutic range was low. Mortality and stroke rates are higher than those reported in other contemporary registries.

SAMe-TT2R2 Score in the Outpatient Anticoagulation Clinic to Predict Time in Therapeutic Range and Adverse Events / Uso do Escore SAMe-TT2R2 em Ambulatório de Anticoagulação para Predição de Tempo na Faixa Terapêutica e de Eventos Adversos

Abstract Background: The SAMe-TT2R2 score was developed to predict which patients on oral anticoagulation with vitamin K antagonists (VKAs) will reach an adequate time in therapeutic range (TTR) (> 65%-70%). Studies have reported a relationship between this score and the occurrence of adverse events. Objective: To describe the TTR according to the score, in addition to relating the score obtained with the occurrence of adverse events in patients with nonvalvular atrial fibrillation (AF) on oral anticoagulation with VKAs. Methods: Retrospective cohort study including patients with nonvalvular AF attending an outpatient anticoagulation clinic of a tertiary hospital. Visits to the outpatient clinic and emergency, as well as hospital admissions to the institution, during 2014 were evaluated. The TTR was calculated through the Rosendaal´s method. Results: We analyzed 263 patients (median TTR, 62.5%). The low-risk group (score 0-1) had a better median TTR as compared with the high-risk group (score ≥ 2): 69.2% vs. 56.3%, p = 0.002. Similarly, the percentage of patients with TTR ≥ 60%, 65% or 70% was higher in the low-risk group (p < 0.001, p = 0.001 and p = 0.003, respectively). The high-risk group had a higher percentage of adverse events (11.2% vs. 7.2%), although not significant (p = 0.369). Conclusions: The SAMe-TT2R2 score proved to be effective to predict patients with a better TTR, but was not associated with adverse events.

Resumo Fundamento: O escore SAMe-TT2R2 foi desenvolvido visando predizer quais pacientes em anticoagulação oral com antagonistas da vitamina K (AVKs) atingirão um tempo na faixa terapêutica (TFT) adequado (> 65%-70%) no seguimento. Estudos também o relacionaram com a ocorrência de eventos adversos. Objetivos: Descrever o TFT de acordo com o escore, além de relacionar a pontuação obtida com a ocorrência de eventos adversos adversos em pacientes com fibrilação atrial (FA) não valvar em anticoagulação oral com AVKs. Métodos: Estudo de coorte retrospectivo incluindo pacientes com FA não valvar em acompanhamento em ambulatório de anticoagulação de um hospital terciário. Foi realizada uma avaliação retrospectiva de consultas ambulatoriais, visitas a emergência e internações hospitalares na instituição no período de janeiro-dezembro/2014. O TFT foi calculado aplicando-se o método de Rosendaal. Resultados: Foram analisados 263 pacientes com TFT mediano de 62,5%. O grupo de baixo risco (0-1 ponto) obteve um TFT mediano maior em comparação com o grupo de alto risco (≥ 2 pontos): 69,2% vs. 56,3%, p = 0,002. Da mesma forma, o percentual de pacientes com TFT ≥ 60%, 65% ou 70% foi superior nos pacientes de baixo risco (p < 0,001, p = 0,001 e p = 0,003, respectivamente). Os pacientes de alto risco tiveram um percentual maior de eventos adversos (11,2% vs. 7,2%), embora não significativo (p = 0,369). Conclusões: O escore SAMe-TT2R2 foi uma ferramenta eficaz na predição do TFT em pacientes com FA em uso de AVKs para anticoagulação, porém não se associou à ocorrência de eventos adversos.

Fases pré-analítica, analítica e pós-analítica no monitoramento laboratorial da anticoagulação com antagonistas da vitamina K / Pre-analytical, analytical, and post-analytical phases in laboratory monitoring of anticoagulant therapy with vitamin K antagonists

A trombose é uma doença caracterizada por eventos de hipercoagulabilidade. A terapêutica anticoagulante oral com antagonistas da vitamina K (AVKs) é amplamente indicada para prevenção e/ou controle de distúrbios da coagulação. O manuseio de administração dos AVKs é difícil devido à complexidade da definição da dose. Em geral, o monitoramento de indivíduos submetidos à terapêutica com AVK é realizado pela determinação do tempo de protrombina, em que se avalia o grau de anticoagulação através do coeficiente internacional normatizado. Invariavelmente, o fluxo do processamento laboratorial, que compreende as fases pré-analítica, analítica e pós-analítica, é importante para a fidedignidade dos resultados, repercutindo na conduta médica de forma determinante. O objetivo deste estudo foi a realização de uma revisão da literatura científica descritiva utilizando bases de dados eletrônicos para busca de materiais científicos, como Google Scholar, MEDLINE, LILACS, PubMed, SciELO e Science Direct. Abordamos alguns aspectos relacionados ao fluxo analítico da monitoração laboratorial em um laboratório de análises clínicas. Em conclusão, é necessária uma apropriada condução das fases analíticas para que seja possível o sucesso terapêutico com uso dos AVKs (AU)

Thrombosis is a disease characterized by hypercoagulable events. Oral anticoagulant therapy with vitamin K antagonists (VKAs) is widely indicated for prevention and/or control of coagulation disorders. The administration of VKAs is difficult because of the complexity of dose setting. In general, individuals submitted to VKA therapy are monitored by prothrombin time, in which the degree of anticoagulation is assessed by the international normalized ratio. Invariably, the flow of laboratory processing, which comprises pre-analytical, analytical, and post-analytical phases, is of importance to the trustworthiness of results, with significant consequences to the medical practice. The purpose of this study was to carry out a review of the scientific literature using electronic databases to search for scientific materials, such as Google Scholar, MEDLINE, LILACS, PubMed, SciELO, and Science Direct. We discuss some aspects related to the analytical flow of laboratory monitoring in a clinical laboratory. In conclusion, appropriate management of the analytical phases is necessary so that therapeutic success using VKAs is possible (AU)