Anticoagulación precoz con warfarina en pacientes sometidos a sustitución valvular aórtica por bioprótesis: ensayo prospectivo randomizado: análisis interino / Early anticoagulation with warfarin in patients undergoing bioprosthetic aortic valve replacement: randomized prospective trial: interim analysis / Anticoagulação precoce com varfarina em pacientes submetidos à troca valvar aórtica por bioprótese: ensaio prospectivo randomizado: análise provisória

Introducción: aunque las bioprótesis son menos trombogénicas que las válvulas mecánicas; la trombosis de estas es una entidad cada vez más reconocida como causa de disfunción protésica potencialmente reversible. No está definido el beneficio de la anticoagulación rutinaria versus antiagregación plaquetaria luego de la sustitución valvular aórtica (SVA) por bioprótesis. La anticoagulación precoz podría asociarse a menores gradientes transprotésicos con similar riesgo de complicaciones. Objetivos: el objetivo primario es determinar si existe una diferencia significativa en la variación del gradiente transprotésico medio al año de la SVA entre las dos estrategias de tratamiento antitrombótico. Los objetivos secundarios son la comparación de la variación del gradiente máximo y del área valvular aórtica, y parámetros clínicos que incluyen la Clase Funcional de la New York Heart Association, las tasas de sangrado mayor y menor y la incidencia de eventos embólicos. Este trabajo representa el análisis interino a 3 meses de un proyecto a más largo plazo, y se propone mostrar los resultados preliminares de los puntos finales previamente definidos. Métodos: se presenta el análisis interino de un ensayo randomizado multicéntrico. Todos los pacientes sometidos a SVA por bioprótesis porcinas fueron sucesivamente reclutados en dos centros de cirugía cardíaca desde el 01/01/2019 hasta el 01/09/2019. El grupo anticoagulación recibió warfarina durante los primeros 3 meses y ambos recibieron aspirina a largo plazo. Se realizaron instancias de seguimiento clínicas y ecocardiográficas antes del alta, a los 3 meses y al año. Resultados: se reclutaron 107 pacientes; 46% de ellos fueron randomizados al grupo anticoagulación y 54% al grupo control. No existieron diferencias en las características basales. Tampoco existieron diferencias significativas entre ambos grupos en la variación entre el alta y los 3 meses del área valvular protésica, coeficiente de obstrucción, gradiente máximo ni gradiente medio ni en la clase funcional. En cuanto a las complicaciones, no existieron eventos embólicos y los sangrados no difirieron significativamente entre ambos grupos. Conclusiones: la anticoagulación no modificó la variación de los gradientes transprotésicos a los 3 meses. Asimismo, no produjo mayor incidencia de efectos adversos. Todavía no está dilucidado si la anticoagulación precoz con warfarina luego de la SVA tiene impacto en los resultados a largo plazo.

Introduction: although bioprostheses are less thrombogenic than mechanical valves, bioprosthesis valve thrombosis is an increasingly recognized entity that can cause potentially reversible prosthetic valve dysfunction. There is a lack of consensus whether to use anticoagulation after aortic valve replacement (AVR) or antiplatelet therapy. Our hypothesis is that early anticoagulation is associated with lower transprosthetic gradients with similar risk of complications. Objective: primary objective is to determine if there is a significant difference in the variation of the mean transprosthetic gradient (ΔGm) one year after SVA between the two antithrombotic treatment strategies. Secondary objectives are the comparison of the variation of maximum gradient and aortic valve area, and clinical parameters including NYHA functional class, major and minor bleeding rates, and the incidence of embolic events. This work represents the 3-month interim analysis of a longer-term project, and is intended to show the preliminary results of the previously defined end points. Methods: this is an interim analysis of a multicenter randomized trial. All patients who underwent AVR by porcine bioprostheses were successively recruited in two cardiac surgery centers in Montevideo between 01/01/2019 and 01/09/2019. The anticoagulation group received warfarin for 3 months. Both groups received aspirin. Clinical and echocardiographic follow-up consultations were performed before discharge, at 3 months, and at 1 year. Results: 107 patients were recruited, 46% were randomized to the anticoagulation group and 54% to the control group. There were no differences in baseline characteristics. There were no significant differences between the two groups in the variation between discharge and 3 months of effective orifice area, doppler velocity index, peak gradient and mean gradient. There were also no differences between both groups in functional class. Regarding complications, there were no embolic events and bleeding did not differ significantly. Conclusions: in this study, anticoagulation did not modify the variation of transprosthetic gradients at 3 months. Likewise, it did not produce a higher incidence of adverse effects. It remains unclear whether early anticoagulation with warfarin after AVR has an impact on long-term outcomes.

Introdução: embora as biopróteses sejam menos trombogênicas que as mecânicas, a trombose de biopróteses é uma entidade cada vez mais reconhecida como causa de disfunção protética potencialmente reversível. A anticoagulação de rotina após a substituição da valva aórtica por bioprótese (SVA) não está definida. Nossa hipótese é que a anticoagulação precoce está associada a menores gradientes transprotéticos com risco semelhante de complicações. Objetivo: o objetivo principal é determinar se há uma diferença significativa na variação do gradiente transprotético médio (ΔGm) um ano após SVA entre as duas estratégias de tratamento antitrombótico. Os objetivos secundários são a comparação da variação do gradiente máximo e da área valvar aórtica e parâmetros clínicos, incluindo NYHA CF, taxas de sangramento maior e menor e incidência de eventos embólicos. Este trabalho representa a análise intercalar de 3 meses de um projeto de longo prazo, e pretende mostrar os resultados preliminares dos pontos finais previamente definidos. Métodos: apresenta-se a análise interina de um estudo multicêntrico randomizado. Todos os pacientes submetidos a SVA por biopróteses suínas foram sucessivamente recrutados em dois centros de cirurgia cardíaca em Montevidéu, durante um período de recrutamento de 1/1/2019 a 1/9/2019. O grupo de anticoagulação recebeu warfarina por 3 meses. Ambos os grupos receberam aspirina. Foram realizadas consultas médicas clínicas e ecocardiográficas antes da alta, aos 3 meses e ao 1 ano. Resultados: foram recrutados 107 pacientes, 46% foram randomizados para o grupo anticoagulação e 54% para o grupo controle. Não houve diferenças nas características basais. Não houve diferenças significativas entre os dois grupos da variação entre alta e 3 meses na área valvar, coeficiente de obstrução, gradiente máximo ou gradiente médio. Também não houve diferenças entre os dois grupos na classe funcional. Em relação às complicações, não houve eventos embólicos e sangramentos não diferiram significativamente. Conclusões: neste estudo, a anticoagulação não modificou a variação dos gradientes transprotéticos aos 3 meses. Da mesma forma, não produziu maior incidência de efeitos adversos. Ainda não está claro se a anticoagulação precoce com varfarina após SVA tem impacto nos resultados a longo prazo.

Uso de anticoagulantes orales directos en pacientes con fibrilación auricular post implante de TAVI: resultados de una encuesta internacional / Use of anticoagulants in patients with atrial fibrillation undergoing transcatheter aortic valve implantation

BACKGROUND: Transcatheter Aortic Valve Implantation (TAVI) is beneficial in patients with symptomatic severe Aortic Stenosis (AS). There is no consensus about the best anticoagulation strategy for patients with a recent TAVI and with atrial fibrillation (AF). Direct oral anticoagulants (DOACs) are effective to prevent embolic events with a significant lower incidence of bleeding. There is scarce evidence about the use of these drugs in patients undergoing TAVI. AIM: To assess the management of anticoagulation at the moment of discharge of patients with AF and TAVI. Material and Methods: A four question survey was sent to cardiologists involved in TAVI programs in different international centers. Results: The survey was answered by 72 interventional cardiologists. Even with the lack of randomized evidence, in most of the scenarios DOACs are prescribed at discharge in patients with indication for anticoagulation. Also, in patients with high bleeding risk, most cardiologists would perform a left atrial appendage closure. In patients with concomitant coronary artery disease, if a stent was recently implanted, prescription of the combination of a DOAC and one antiplatelet drug was the most common answer. In patients with a former coronary angioplasty, DOAC or Warfarin was the therapy of choice. CONCLUSIONS: In the absence of randomized data, interventional cardiologists prescribe DOACs at discharge to patients with AF and TAVI, without following current guidelines in most cases.

Bleeding associated with self-medication in warfarin users: A prospective observational study in Ijuí (Brazil)

Abstract Warfarin has been associated with bleeding and venous thromboembolism. Objective: This study aimed to estimate the association between bleeding and concomitant self-medication, and the incidence of adverse drug reactions in patients using warfarin. Setting: the public health network of Ijuí, a municipality in southern Brazil. This was an open prospective cohort, conducted for a period of 18 months with users of warfarin, treated at the public health service. The association between bleeding and self-medication was evaluated by means of the Cox Model with left truncation, using the time variable. Main outcome measurement: bleeding reported in the follow-up. Cases of thromboembolism and death were also registered. All patients treated with warfarin in the public health system of the municipality (98) were identified. Sixty-eight were interviewed and followed up, of whom 63 completed follow-up and five died during the study. Bleeding rates of 37.7 /100 patients/year, thromboembolism of 4.8/100 patients / year and deaths of 4.8 /100 patients / year were observed. The results showed that patients, who take warfarin and self-medicated present a two-fold increased bleeding, compared with those who do not self-medicate. The bleeding risk associated with self-medication ranged from 2.001 to 2.685; those values maintained their significance even when adjusted for number of interactions, CYP polymorphism, TTR and age in COX analysis. These results greatly suggest the need for providing greater assistance to patients who take anticoagulant medications with the purpose of reducing self-medication and consequently, adverse reactions.

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)

Use of a mobile application for the control of anticoagulation with warfarin: a cluster randomized controlled clinical trial - Ijui/RS/Brazil

Abstract To evaluate the effectiveness of an anticoagulation protocol adapted in a mobile application (appG) for patients using warfarin. This was a cluster randomized controlled clinical trial carried out in basic health centers of Ijui, RS, Brazil, between April and October 2017. The appG was installed on the cell phones of all physicians belonging to the intervention group. Primary outcomes were bleeding and thrombosis, and secondary outcomes were changes in the dose of warfarin, use of new drugs, drug interactions, search for health services, and remaining on the target international normalized ratio. Thirty-three patients belonging to 11 basic health centers were included in this study. From these, 15 patients were in the intervention group which used the appG, and 18 were in the control group. After 6 months, patients in the appG group had fewer bleeding events (7% versus 50%, p-value=0.028) and a lower weekly dose of warfarin (29.3 ± 9.7 mg versus 41.7 ± 12.5 mg, p-value=0.030) when compared to the control group. The anticoagulation protocol adapted in a mobile app reduced bleeding in patients using warfarin.

Polymorphism of the CYP2C9 and VKORC1 genes in patients on the public health system of a municipality in Southern Brazil / Polimorfismo dos genes CYO2C9 e VKORC1 em pacientes do Sistema Público de Saúde em um município do Sul do Brasil

Abstract Background Genetic factors can be responsible for part of the populational and interindividual differences observed in warfarin users. Objectives To identify occurrence of polymorphisms of the CYP2C9 and VKORC1 genes in patients taking warfarin and relate these profiles to their medication dosages and the Time in Therapeutic Range (TTR). Methods Monthly interviews were conducted for data collection. Data were collected on demographic characteristics and medications in use, especially warfarin, including reason for prescription and weekly dose. TTR was calculated as the percentage of days with international normalized ratio (INR) between 2 and 3. The CYP2C9 and VKORC1 genes were analyzed at a Human Genetics Laboratory. Results 49 patients (74.2%) had polymorphisms of the CYP2C9 and/or VKORC1 genes; the remaining 17 (25.8%) did not have these polymorphisms. The average weekly dose of warfarin was lower among those who had a polymorphism for any of the genes compared to those who did not, with a significant difference (p = 0.035). The mean TTR was also lower among patients with polymorphism. However, the difference between the two groups was not significant for this variable (p = 0.438). Conclusions An association was observed between the polymorphisms and the warfarin doses taken by the patients. However, there was no association with adverse events or the time spent within the therapeutic range in this sample.

Resumo Contexto Fatores genéticos podem ser responsáveis por parte das diferenças populacionais e interindividuais observadas em usuários de varfarina. Objetivos Identificar a ocorrência de polimorfismo dos genes CYP2C9 e VKORC1 em pacientes em uso de varfarina e relacionar esses perfis com a dose do medicamento e o tempo no intervalo terapêutico. Métodos Foram realizadas entrevistas mensais para a coleta de dados. Foram reunidos dados sobre características demográficas e medicamentos em uso, principalmente sobre varfarina, como motivo da prescrição e dose semanal. O tempo no intervalo terapêutico foi calculado como a porcentagem de dias com razão normalizada internacional entre os valores 2 e 3. Os genes CYP2C9 e VKORC1 foram analisados em laboratório de Genética Humana. Resultados Entre os participantes, 49 pacientes (74,2%) apresentaram polimorfismo dos genes CYP2C9 e/ou VKORC1; os 17 restantes (25,8%) não apresentaram esses polimorfismos. A dose média semanal de varfarina foi menor entre os que apresentaram polimorfismo para algum dos genes em comparação aos que não apresentaram, com diferença significativa (p = 0,035). O tempo no intervalo terapêutico médio também foi menor entre os pacientes com polimorfismo. Porém, não houve diferença significativa entre os dois grupos para essa variável (p = 0,438). Conclusões Foi observada associação entre os polimorfismos e a dose de varfarina utilizada pelos pacientes; no entanto, não houve associação com eventos adversos e o tempo de permanência na faixa terapêutica nessa amostra.

Alopecia em pacientes anticoagulados / Alopecia in anticoagulated patients

Resumo A alopecia é uma complicação comum da terapia anticoagulante que pode ter repercussões psicológicas importantes nos pacientes, especialmente nos do sexo feminino, e interferir na decisão de extensão da anticoagulação. Esta revisão tem como objetivo descrever os mecanismos potencialmente envolvidos na gênese da alopecia durante a terapia anticoagulante, pois eles ainda não estão totalmente esclarecidos, e as terapias existentes, para a adoção das condutas mais adequadas.

Abstract Alopecia is a common complication of anticoagulant therapy that may have important psychological repercussions for patients, especially female patients, and can interfere with the decision to extend anticoagulation. This review aims to describe the mechanisms potentially involved in the genesis of alopecia during anticoagulant therapy, since these are not yet fully understood, and discusses the existing therapies for the most appropriate management.

Interações medicamentosas nos idosos em uso de anticoagulantes orais internados num hospital cardiológico / Drug interactions in elderly people making use of oral anticoagulants and hospitalized in a cardiology hospital / Interacciones medicamentosas en los ancianos en uso de anticoagulantes orales internados en un hospital cardiológico

Objective: The study's purpose has been to relate the drug interactions of oral anticoagulants with other medications used by elderly people hospitalized in a cardiology hospital. Methods: It is a prospective exploratory study with 16 elderly people taking oral anticoagulant, who were hospitalized at a governmental cardiology institution in São Paulo State over the period from November to December 2017. Results: Among 73 medicines prescribed and analyzed in the Micromedex 2.0, 24 (33.3%) interacted with Warfarin, the only prescribed oral anticoagulant. There were found Omeprazole (70; 97.2%); Dipyrone (68; 94.4%); Simvastatin (43; 59.72%); Enoxaparin (42; 58.33%); Amiodarone (29; 40.27%); Sertraline (28; 38.88%); Spironolactone (21; 29.16%); and Atenolol (11; 15.27%), whose interactions could either potentialize or inhibit the anticoagulant action. Considering the interactions, 14 (58.33%) were of moderate severity, 10 (41.66%) of high severity and 14 (58.33%) of fast effect. Conclusion: Polypharmacy and the use of oral anticoagulants in elderly patients bearing heart diseases are common events. Moreover, a better understanding about drug interactions is also required, bearing in mind that they can either potentialize or decrease the anticoagulant effect, with high or moderate severity

Objetivo: Relacionar as interações medicamentosas dos anticoagulantes orais com os medicamentos utilizados por idosos internados em hospital cardiológico. Método: Estudo exploratório, prospectivo, com 16 idosos em uso de anticoagulantes orais, internados numa instituição cardiológica governamental de São Paulo entre novembro e dezembro de 2017. Resultados: Dentre 73 medicamentos prescritos e analisados no Micromedex 2.0, 24 (33,3%) interagiam com a Varfarina, único anticoagulante oral prescrito. Encontrou-se Omeprazol (70;97,2%); Dipirona (68;94,4%); Sinvastatina (43;59,72%); Enoxaparina (42;58,33%); Amiodarona (29;40,27%); Sertralina (28;38,88%); Espironolactona (21;29,16%); e Atenolol (11;15,27%), cujas interações poderiam potencializar ou inibir a ação anticoagulante. Das interações, 14 (58,33%) eram de gravidade moderada, 10 (41,66%) maior e 14 (58,33%) de efeito rápido. Conclusão: A polifarmácia e o uso de anticoagulante oral em idosos cardiopatas é comum e, conhecer as interações medicamentosas, é imperativa, considerando que potencializam ou diminuem a ação anticoagulante, com gravidade maior ou moderada

Objetivo: Relacionar las interacciones medicamentosas de los anticoagulantes orales con los medicamentos utilizados por ancianos internados em um hospital cardiológico. Método:Estudio exploratorio, prospectivo, con 16 ancianos en uso de anticoagulantes orales, internados en una institución cardiológica gubernamental de São Paulo entre noviembre y diciembre de 2017. Resultados:Entre 73 medicamentos prescritos y analizados en el Micromedex 2.0, 24 (33,3%) interactuaban con la Varfarina, único anticoagulante oral prescrito. Se encontró Omeprazol (70, 97,2%); Dipirona (68, 94,4%); Sinvastatina (43, 59,72%); Enoxaparina (42, 58,33%); Amiodarona (29, 40,27%); Sertralina (28, 38,88%); Espironolactona (21, 29,16%); y Atenolol (11, 15,27%), cuyas interacciones podrían potenciar o inhibir la acción anticoagulante. De las interacciones, 14 (58,33%) eran de gravedad moderada, 10 (41,66%) mayor y 14 (58,33%) de efecto rápido. Conclusión: La polifarmacia y el uso de anticoagulante oral en ancianos cardiopatas es común y, conocer las interacciones medicamentosas, es imperativa, considerando que potencian o disminuyen la acción anticoagulante, con gravedad mayor o moderada

Drug interactions and adverse events in a cohort of Warfarin users attending Public Health Clinics / Interações medicamentosas e eventos adversos em uma coorte de usuários de varfarina que freqüentam clínicas de saúde pública

Background: Warfarin is an oral anticoagulant involved in important interactions with foods and other drugs. Objectives: To evaluate the occurrence of adverse events reported by warfarin users and their relationship with drug interactions. Methods: This was an open cohort, prospective study conducted in an 18-month period with warfarin users attending public health clinics of the city of Ijuí, Brazil. Data were collected by means of interviews administered at patients' home every month. Patients' responses were confirmed by review of medical records when patients sought medical care. Data were analyzed by descriptive statistics. Potential drug interactions were evaluated in a database and vitamin K consumption was quantified using a validated method. Results: A total of 68 patients were followed-up; 63 completed the study and 5 died in the study period. Mean number of medications taken by the patients was 9.6 ± 4.5, and mean number of interactions involving warfarin was 2.91 ± 1.52. Most potential interactions increased the risk of bleeding, 61 of them severe interactions and 116 moderate interactions. Eighty-seven episodes of bleeding and 4 episodes of thrombosis were reported by a total of 37 and 4 patients, respectively. At the occurrence of these events, 56.5% of warfarin users were also taking omeprazole, 35.9% were taking simvastatin and 25.0% paracetamol. Most patients had a low vitamin K intake. Conclusions: A high frequency of potential interactions between warfarin and other drugs was detected, but a low intake of foods that could possibly affect the effects of warfarin was observed. Based on our results, it seems prudent to follow patients on warfarin therapy for drug-drug interactions, aiming to control adverse effects and to promote a safe and effective therapy

Evaluation of the Bleeding Intensity of Patients Anticoagulated with Warfarin or Dabigatran Undergoing Dental Procedures / Avaliação da Intensidade de Sangramento de Procedimentos Odontológicos em Pacientes Anticoagulados com Varfarina ou Dabigatrana

Abstract Background: Thrombotic disorders remain one of the leading causes of death in the Western world. Dabigatran appeared as an alternative to warfarin for anticoagulation in the treatment of atrial fibrillation (AF). The risk associated with bleeding due to its use has been documented in several randomized clinical trials, but no large study has examined in detail the risk of bleeding during dental extraction and other dental procedures involving bleeding. Objective: To compare the intensity of bleeding in individuals taking dabigatran or vitamin K antagonist (warfarin) and undergoing dental procedures. Methods: Prospective, single-center, controlled study with one single observer. Patients diagnosed with nonvalvular AF, on warfarin or dabigatran, cared for at a cardiology referral center, and requiring single or multiple dental extractions, were evaluated up to seven days post-extraction. The following outcomes were assessed: bleeding time between the beginning and the end of suture and complete hemostasis; bleeding before the procedure, after 24 hours, 48 hours, 7 days, during and after suture removal (late); p<0.05 was defined as of statistical relevance. Results: We evaluated 37 individuals, 25 in the warfarin group and 12 in the dabigatran group. Age, sex, weight, height, blood pressure, color, schooling, family income and comorbidities were similar between the two groups. Regarding bleeding after 24 hours of the procedure, no one in the dabigatran group had bleeding, whereas 32% in the warfarin group had documented bleeding (p = 0.028). The other variables analyzed did not differ between the groups. Conclusions: This study suggests that, regarding dental extraction, there is no statistically significant difference in the intensity of bleeding of patients taking dabigatran as compared to those taking warfarin. Bleeding 24 hours after the procedure was less frequent among patients on dabigatran.

Resumo Fundamento: Distúrbios trombóticos permanecem como uma das principais causas de morte no mundo ocidental. A dabigatrana surgiu como alternativa à varfarina para a anticoagulação no tratamento da fibrilação atrial (FA). O risco associado a eventos hemorrágicos com a sua utilização foi documentado em vários ensaios clínicos randomizados, mas nenhum grande estudo analisou detalhadamente o risco de hemorragia durante a extração dentária e em outros procedimentos odontológicos que envolvam sangramentos. Objetivo: Em indivíduos submetidos a procedimentos odontológicos, avaliar a intensidade de sangramento com o uso de dabigatrana em comparação ao uso de anticoagulante oral antagonista da vitamina K (varfarina). Métodos: Estudo prospectivo, controlado, unicêntrico, observador único. Pacientes com diagnóstico de FA não valvar atendidos em um centro de referência em cardiologia e com indicação de anticoagulação que necessitavam de tratamento odontológico para exodontia única ou múltipla, estando em uso de varfarina ou dabigatrana e avaliados até sete dias pós-exodontia. Foram avaliados os efeitos sobre: tempo de sangramento entre o início e o fim da sutura e hemostasia completa; sangramento antes do procedimento, após 24 e 48 horas, 7 dias, durante e após a remoção da sutura (tardio), sendo considerado como estatisticamente significativo valor de p < 0,05. Resultados: Foram avaliados 37 indivíduos, sendo 25 no grupo varfarina e 12 no dabigatrana. Idade, sexo, peso, altura, pressão arterial, cor, escolaridade, renda familiar e comorbidades foram semelhantes nos dois grupos. Em relação ao sangramento 24 horas após o procedimento, ninguém do grupo dabigatrana apresentou sangramento, que esteve presente em 32% do grupo varfarina (p = 0,028). Não houve diferenças entre os grupos em relação às outras variáveis analisadas. Conclusões: Os dados deste estudo permitem sugerir que, em indivíduos submetidos a procedimento odontológico de exodontia, não há diferença estatisticamente significante na intensidade de sangramento em uso de dabigatrana em comparação ao uso de varfarina. Há uma menor frequência de sangramento 24 horas após o procedimento nos indivíduos em uso de dabigatrana.

Arritmias cardíacas na sala de emergência e UTI. Anticoagulação do paciente com FA aguda submetido a cardioversão: já podemos contar com os novos anticoagulantes orais? / Cardiac arrhythmias in the emergency room and ICU. Anticoagulation of the patient with acute af undergoing cardioversion: can we rely on the new oral antioagulants?

A fibrilação atrial (FA) é a arritmia cardíaca mais comum na população com uma prevalência de 1-2%, além disso, está associada a um risco, aproximadamente cinco vezes maior de acidente vascular cerebral do que na população em geral. A anticoagulação é a melhor maneira de prevenir os eventos tromboembólicos. A varfarina é utilizada há décadas como uma droga segura e eficaz, desde que rigorosamente controlada. Nos últimos anos, foram desenvolvidas novas classes de anticoagulantes orais: inibidores diretos da trombina e inibidores do fator Xa, conhecidos como anticoagulantes orais de ação direta (DOACs). Tanto a cardioversão elétrica quanto a cardioversão farmacológica estão associadas a um maior risco de eventos tromboembólicos durante o primeiro mês após o procedimento (5-7%). No entanto, com a utilização de nticoagulantes essa taxa é inferior a 1%. No presente artigo, faremos uma revisão das principais evidências científicas relacionadas ao uso da dabigatrana, rivaroxabana, apixabana e edoxabana durante a cardioversão e uma abordagem prática com o manejo antitrombótico em diferentes cenários clínicos (cardioversão em pacientes com uso prévio de DOACs, cardioversão em pacientes com FA com duração maior ou menor que 48 horas sem anticoagulação)

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice with a prevalence of 1-2%, and is associated with an almost 5-fold increase in the risk of stroke compared to the general population. Anticoagulation is the best way to prevent thromboembolic events. Warfarin has been used for decades as a safe and effective drug, provided it is strictly controlled. In recent years, new classes of oral anticoagulants have been developed: direct thrombin inhibitors and factor Xa inhibitors, known as direct oral anticoagulants (DOACs). Both electrical and pharmacological cardioversion are associated with an increased risk of thromboembolic events during the first month after the procedure (5-7%). However, with the use of anticoagulants, this rate is less than 1%. In this article, we will review the main scientific evidence related to the use of dabigatran, rivaroxaban, apixaban and edoxaban during cardioversion and a practical approach with antithrombotic management in different clinical scenarios (cardioversion of patients in previous use of DOACs, cardioversion of patients not using oral anticoagulants with episodes of AF longer or shorter than 48 h)

Nível de informação e adesão à terapia de anticoagulação oral com varfarina em pacientes acompanhados em ambulatório de atenção primária à saúde / Knowledge and information levels and adherence to oral anticoagulant therapy with warfarin in patients attending primary health care services

A anticoagulação oral com varfarina é usada por milhões de pacientes em todo o mundo, apresentando segurança e eficácia bem estabelecidas. Ainda assim, na atenção primária à saúde, os anticoagulantes estão entre as classes de medicamentos mais associadas a erros de medicação fatais. Objetivo: Verificar o nível de informação e a adesão ao tratamento com varfarina em pacientes acompanhados em ambulatório de atenção primária à saúde. Método: Foi realizado um estudo transversal de uma coorte prospectiva com 60 pacientes em uso de varfarina no município de Ijuí, Rio Grande do Sul. Utilizou-se questionário para verificar o nível de informações dos usuários quanto à prescrição e o nível das informações prestadas pela equipe de saúde aos usuários. A Escala de Adesão Terapêutica de Morisky de Oito Itens (MMAS-8) e o coeficiente internacional normatizado ( international normalized ratio , INR) foram usados para verificar a adesão ao tratamento. Resultados: Os resultados foram expressos em valores absolutos e relativos e razão de prevalência, com seu respectivo intervalo de confiança de 95%. Verificou-se que 83,3% dos participantes tiveram nível de informação insuficiente prestada pela equipe de saúde, 50,0% não souberam informar sobre o uso correto do medicamento, 86,7% foram não aderentes ao tratamento segundo a MMAS-8, e 63,3% estavam fora do intervalo terapêutico adequado. Conclusão: Neste estudo, observou-se a necessidade de melhorar a qualidade das informações prestadas aos usuários e criar estratégias para adesão ao tratamento, visando à segurança do paciente em tratamento com varfarina na atenção primária à saúde.

Oral anticoagulation therapy with warfarin is widely used around the world and its safety and efficacy are well-established. Nevertheless, anticoagulants are among the drug classes most associated with fatal medication errors in primary health care. Objective: To investigate patient knowledge, the level of information provided, and medication adherence in patients treated with warfarin at a primary health care service. Method: A cross-sectional study of a prospective cohort of 60 patients on warfarin treatment in the town of Ijuí, Rio Grande do Sul, Brazil. A questionnaire was administered to test patients' knowledge about their prescriptions and the level of information provided by the health team. The 8-item Morisky Medication Adherence Scale (MMAS-8) and International Normalized Ratio (INR) were used to verify adherence to treatment. Results: The results were expressed in absolute and relative values and prevalence ratios were calculated, with respective 95% confidence intervals. It was found that 83.3% of the participants had been given insufficient information by the health team, 50% did not know how to use the medication correctly, 86.7% were not adherent to the treatment according to MMAS-8 and 63.3% were outside of the correct INR range. Conclusion: In this study, we observed a need to improve the quality of information provided to users and to develop strategies to improve adherence to treatment, to ensure the safety of patients treated with warfarin in primary health care services.

Anticoagulation in patients with cardiac manifestations of Chagas disease and cardioembolic ischemic stroke / Anticoagulação nas manifestações cardíacas da doença de Chagas e acidente vascular cerebral isquêmico cardioembólico

ABSTRACT Objectives To describe anticoagulation characteristics in patients with cardiac complications from Chagas disease and compare participants with and without cardioembolic ischemic stroke (CIS). Methods A retrospective cohort of patients with Chagas disease, using anticoagulation, conducted from January 2011 to December 2014. Results Forty-two patients with Chagas disease who were using anticoagulation were studied (age 62.9±12.4 years), 59.5% female and 47.6% with previous CIS, 78.6% with non-valvular atrial fibrillation and 69.7% with dilated cardiomyopathy. Warfarin was used in 78.6% of patients and dabigatran (at different times) in 38%. In the warfarin group, those with CIS had more medical appointments per person-years of follow-up (11.7 vs 7.9), a higher proportion of international normalized ratios within the therapeutic range (57% vs 42% medical appointments, p = 0.025) and an eight times higher frequency of minor bleeding (0.64 vs 0.07 medical appointments). Conclusion Patients with Chagas disease and previous CIS had better control of INR with a higher frequency of minor bleeding.

RESUMO Objetivos descrever as características da anticoagulação em pacientes com manifestações cardíacas da doença de Chagas (MCDC) e comparar os participantes com sem acidente vascular cerebral isquêmico cardioembólico (AVCIC). Resultados 42 pacientes com MCDC em anticoagulação foram estudados (62,9 ± 12,4 anos), 59,5% do sexo feminino e 47,6% com AVCIC prévio, 78,6% portadores de fibrilação atrial não valvar e 69,7% com cardiomiopatia dilatada. Varfarina foi utilizada em 78,6% dos pacientes e dabigatrana em 38% (em momentos diferentes). No grupo da varfarina, aqueles com AVCIC tiveram mais consultas médicas por pessoas-ano de seguimento (11,7 vs 7,9), maior taxa de RNI na faixa terapêutica (57% vs 42% consultas médicas, p = 0,025) e uma frequência oito vezes maior de sangramento menor (0,64 vs. 0,07 consultas médicas). Conclusão pacientes com MCDC e AVCIC prévio têm melhor controle de RNI com maior frequência de sangramento menor.

Therapeutic itinerary: trajectory for resolution of adverse events of patients using warfarin in Southern Brazil

Warfarin is the most used anticoagulant in primary health care. Due to the narrow therapeutic index, its users are more susceptible to adverse events. The objective of this study was to describe the itinerary of the public health sector patients for resolution of adverse events related to warfarin. It is a prospective open cohort, held for a period of 18 months with warfarin users of the Brazilian public health system. Data were collected by monthly interviews and from patient records. Results: Sixty nine patients were interviewed, 64 of them completed monitoring and five died. Bleeding and venous thromboembolism were more frequent in patients starting treatment. It was observed that when adverse events have occurred, in most cases the patient held self-care at home (57%). During the follow-up, five patients were hospitalized for bleeding. Approximately half of the patients did not present their INR exams to the doctor. Conclusions: This study demonstrates weaknesses in caring for these patients and the need to accompany them, aiming to standardize and guide the itinerary of the anticoagulated patient to solve their problems and improve safety in drug treatment, with less cost to the public health system.

Terapia anticoagulante no idoso: foco na fibrilação atrial / Anticoagulant therapy in the elderly: focus on atrial fibrillation

O uso da terapia anticoagulante em idosos tem sido muito discutido, principalmente após o surgimento dos anticoagulantes de ação direta (DOACs). Por anos, os antagonistas da vitamina K (representados principalmente pela varfarina) foram a única opção de prevenção de acidente vascular cerebral (AVC) e de embolia sistêmica (ES) em pacientes com fibrilação atrial (FA), bem como prevenção e tratamento de tromboembolismo venoso (TEV). Os DOACs tornaram-se opção melhor que a varfarina na população idosa por serem tão ou mais eficazes e apresentarem um risco de sangramento igual ou menor e risco mais baixo de hemorragia intracraniana. Além disso, têm menor interação medicamentosa e alimentar e não requerem monitoramento laboratorial contínuo. A população idosa tem sido subtratada devido aos riscos e aos receios dos profissionais quanto ao uso dos anticoagulantes. Seja pelo risco de quedas, de sangramento, polifarmácia ou presença de comprometimento cognitivo, os riscos devem ser muito bem avaliados e adequadamente abordados, uma vez que o benefício da anticoagulação é evidente nos idosos. A idade não é contraindicação para terapia anticoagulante e seu uso diminui a mortalidade e aumenta a sobrevida livre de incapacidade

The use of anticoagulant therapy in the elderly has been much discussed, especially after the development of direct oral anticoagulants (DOACs). For years, the vitamin K antagonists (represented mainly by warfarin) were the only option for stroke and systemic embolism (SE) prevention in patients with atrial fibrillation (AF), as well as for the treatment and prevention of venous thromboembolism (VTE). DOACs have become a better option than warfarin in the elderly population because they are as good as or more effective and present an equal or lesser bleeding risk and a lower risk of intracranial hemorrhage. In addition, they have limited drug and food interactions and do not require continuous laboratory monitoring. The elderly population has been under-treated because of the risks and professionals fears prescribing anticoagulants. Whether due to the risk of falls, bleeding, polypharmacy, or the presence of cognitive impairment, the risks should be well evaluated and appropriately addressed, since the benefit of anticoagulation is evident in the elderly. Age is not a contraindication for anticoagulant therapy, and its use decreases mortality and increases disability-free survival

Terapias anticoagulantes na doença renal crônica / Anticoagulant therapies in chronic renal disease

Os pacientes com doença renal crônica (DRC) têm tendências hemorrágicas e trombóticas e, por isso, a indicação de anticoagulantes é complexa nos indivíduos com fibrilação atrial (FA). A FA é a arritmia mais frequente na DRC, sendo o tromboembolismo e o ictus suas principais complicações. A introdução de novos anticoagulantes orais diretos (DOACs) tem se mostrado superior aos antagonistas da vitamina K, tanto na prevenção de tromboembolismos sistêmicos como no risco de sangramento. Contudo, devem ser prescritos com cautela nesse grupo de pacientes. Para os indivíduos com DRC e clearance renal entre 30 e 50 ml/min, as doses da dabigatrana e da rivaroxabana devem ser reduzidas, no caso de pacientes com elevado risco de sangramento, não havendo necessidade de reduzir as doses de apixabana e edoxabana. Em pacientes com clearance renal entre 15 e 29 ml/min o uso da dabigatrana é contraindicado, a rivaroxabana e a edoxabana não exigem ajuste terapêutico e a dose de apixabana deve ser ajustada. Nenhum dos DOACs é indicado em pacientes com clearance renal < 15 mg/min. Outro problema da terapêutica com os DOACs é o custo do medicamento, muito superior aos dos antagonistas da vitamina K, trazendo algumas implicações clínicas relevantes: suspensão terapêutica por restrições econômicas, que mesmo quando transitória, coloca o paciente em risco de eventos tromboembólicos devido à perda rápida de seus efeitos anticoagulantes e pela possibilidade de hipercoagulabilidade paradoxal. A maior parte da população é tratada em hospitais públicos e recebe os antagonistas de vitamina K. Por isso, enquanto a relação custo-efetividade dos DOACs não for esclarecida, a prevenção e o tratamento de pacientes com DRC e FA com os antagonistas de vitamina K estão consagrados e podem trazer benefícios para esse grupo de pacientes

Patients with chronic renal disease (CRD) have hemorrhagic and thrombotic tendencies, therefore the indication of anticoagulants is complex in individuals with atrial fibrillation (AF). AF is the most frequent arrhythmia in CRD, and thromboembolism and cerebral stroke are its main complications. The introduction of new oral anticoagulants (DOACs) has proven to be superior to vitamin K antagonists in preventing systemic thromboembolisms and bleeding risk. However, they should be prescribed with caution in this group of patients. For individuals with CRD and renal clearance between 30 and 50 ml/min, the doses of dabigatran and rivaroxaban should be reduced, in the case of patients with high risk of bleeding, and it is not necessary to reduce the doses of apixaban and edoxaban. In patients with renal clearance between 15 and 29 ml/min, the use of dabigatran is contraindicated, rivaroxaban and edoxaban do not require therapeutic adjustment, and the dose of apixaban should be adjusted. No DOACs is indicated in patients with renal clearance < 15 mg/min. Another problem with DOACs therapy is the cost of the medication, which is much higher than that of vitamin K antagonists, with some important clinical implications: therapeutic suspension due to economic restrictions, even if temporary, place the patient at risk of thromboembolic events due to the rapid loss of anticoagulant effects and the possibility of paradoxical hypercoagulability. Most of the population is treated in public hospitals, and receives vitamin K antagonists. Therefore, while the cost-effectiveness ratio of DOACs has not been clarified, prevention and treatment of patients with CRD and AF with vitamin K antagonists is consecrated, and can bring benefits for this group of patients