Anticoagulantes Orais Diretos versus Antagonistas da Vitamina K para Trombo Ventricular Esquerdo: Uma Metanálise com Análise Sequencial de Ensaios / Direct Oral Anticoagulants versus Vitamin K Antagonists for Left Ventricular Thrombus: A Meta-Analysis with Trial Sequential Analysis

Resumo Fundamento Os antagonistas da vitamina K (AVKs) são o tratamento de primeira linha recomendado para trombo ventricular esquerdo (TVE); entretanto, os anticoagulantes orais diretos (AODs) têm sido considerados uma terapia alternativa. Objetivos Avaliar a eficácia e a segurança dos AODs em comparação com a terapia com AVKs em pacientes com TVE. Métodos PubMed, Embase e Cochrane foram sistematicamente pesquisados em busca de ensaios clínicos randomizados ou estudos de coorte que comparassem AODs versus AVKs para TVE. As razões de risco (RR) foram calculadas para desfechos binários, com intervalos de confiança (IC) de 95%. A significância estatística foi definida como valor de p < 0,05. Resultados Foram incluídos um total de 4 ensaios clínicos randomizados e 29 estudos de coorte, com 4.450 pacientes designados para AODs ou AVKs. Não houve diferença significativa entre os grupos para acidente vascular cerebral ou eventos embólicos sistêmicos (AVC/EES) (RR 0,84; IC 95% 0,65 a 1,07; p = 0,157), acidente vascular cerebral (RR 0,73; IC 95% 0,48 a 1,11; p = 0,140), eventos embólicos sistêmicos (EES) (RR 0,69; IC 95% 0,40 a 1,17; p = 0,166), resolução do trombo (RR 1,05; IC 95% 0,99 a 1,11; p = 0,077), qualquer sangramento (RR 0,78; IC 95% 0,60 a 1,00; p = 0,054), sangramento clinicamente relevante (RR 0,69; IC 95% 0,46 a 1,03; p = 0,066), sangramento menor (RR 0,73; IC 95% 0,43 a 1,23; p = 0,234), sangramento maior (RR 0,87; IC 95% 0,42 a 1,80; p = 0,705) e mortalidade por todas as causas (RR 1,05; IC 95% 0,79 a 1,39; p = 0,752). Em comparação com AVKs, a rivaroxabana reduziu significativamente AVC/EES (RR 0,35; IC 95% 0,16 a 0,91; p = 0,029) e EES (RR 0,39; IC 95% 0,16 a 0,95; p = 0,037). Conclusões Os AODs tiveram uma taxa semelhante de eventos tromboembólicos e hemorrágicos, bem como de resolução do trombo, em comparação com os AVKs no tratamento de TVE. A terapia com rivaroxabana teve uma redução significativa nos eventos tromboembólicos, em comparação com os AVKs.

Abstract Background Vitamin K antagonists (VKAs) are the recommended first-line treatment for left ventricular thrombus (LVT); however, direct oral anticoagulants (DOACs) have been considered an alternative therapy. Objectives To evaluate the efficacy and safety of DOACs compared with VKAs therapy in patients with LVT. Methods PubMed, Embase, and Cochrane were systematically searched for randomized clinical trials or cohort studies that compared DOACs versus VKAs for LVT. Risk ratios (RRs) were computed for binary endpoints, with 95% confidence intervals (95% CIs). Statistical significance was defined as p value < 0.05. Results A total of 4 randomized clinical trials and 29 cohort studies were included, with 4,450 patients assigned to either DOACs or VKAs. There was no significant difference between groups for stroke or systemic embolic (SSE) events (RR 0.84; 95% CI 0.65 to 1.07; p = 0.157), stroke (RR 0.73; 95% CI 0.48 to 1.11; p = 0.140), systemic embolic (SE) events (RR 0.69; 95% CI 0.40 to 1.17; p = 0.166), thrombus resolution (RR 1.05; 95% CI 0.99 to 1.11; p = 0.077), any bleeding (RR 0.78; 95% CI 0.60 to 1.00; p = 0.054), clinically relevant bleeding (RR 0.69; 95% CI 0.46 to 1.03; p = 0.066), minor bleeding (RR 0.73; 95% CI 0.43 to 1.23; p = 0.234), major bleeding (RR 0.87; 95% CI 0.42 to 1.80; p = 0.705), and all-cause mortality (RR 1.05; 95% CI 0.79 to 1.39; p = 0.752). Compared with VKAs, rivaroxaban significantly reduced SSE events (RR 0.35; 95% CI 0.16 to 0.91; p = 0.029) and SE events (RR 0.39; 95% CI 0.16 to 0.95; p = 0.037). Conclusions DOACs had a similar rate of thromboembolic and hemorrhagic events, as well as thrombus resolution, compared to VKAs in the treatment of LVTs. Rivaroxaban therapy had a significant reduction in thromboembolic events, compared to VKAs.

A study on drug utilization pattern of anticoagulants in post-cardiac surgeries at a tertiary care hospital

Background: The study is being carried out mainly to understand the prevention of coagulation of blood after a patient undergoing various types of cardiac surgeries, using different anticoagulation therapies suitable to particular types of cardiac surgery. This study was conducted to know the types of anticoagulants prescribed to patients who have undergone different types of cardiac surgeries along with the prescribed anticoagulants. Methods: The study method used was a retrospective and prospective observational study carried out on 50 patients who underwent cardiac surgeries in the department of cardiology and medicine. Results: A total of 50 patients were enrolled for this study who satisfied the inclusion criteria, out of which 64% of patients were males, and 36% were females. The highest number of patients were found to be in between the age group of 61-70 yrs (34%), whereas age group between 51-60 yrs (28%), age group 71 and above (18%), 41-50 (14%), 21-30 yrs (4%) and 18-20 yrs (2%) respectively. Most of the patients had undergone Coronary Artery bypass grafting. It was seen that the highest Anticoagulant being prescribed was Heparin in most of the post-cardiac surgeries. Whereas drugs like dalteparin, acenocoumarol, and warfarin were prescribed the majority in valvular heart surgeries. Conclusions: Various cardiac surgeries were taken into consideration for the study. The most common anticoagulants prescribed were heparin, dalteparin, acenocoumarol, and warfarin in coronary artery bypass surgery and valvular heart surgeries respectively.

Study on the Knowledge-Attitude-Practice questionnaire for patients receiving oral anticoagulant therapy based on the Delphi method / 中国药房

OBJECTIVE To develop a questionnaire of the Knowledge-Attitude-Practice （KAP） for patients receiving oral anticoagulant therapy. METHODS Under the guidance of the theory of KAP， literature analysis and interview method were used to design the initial KAP questionnaire for patients treated with oral anticoagulants. Delphi method was adopted to consult the initial questionnaire and modify the questionnaire based on expert suggestions to form the final questionnaire. RESULTS Two rounds of consultation were conducted with 18 experts， and 18 questionnaires were sent out and recovered in each round， so the positive coefficient of experts was 100%. The expert authority coefficient was 0.94. The average importance scores for all dimensions， factors， and items of the questionnaire in both rounds were ≥4 points. The coefficient of variation was ≤0.25. The Kendall’s concordance coefficient for the overall questionnaire and the three dimensions of knowledge， attitude， and practice ranged from 0.09 to 0.34 （all P＜0.05）. Following the first round of expert consultation， four items were modified， two items were deleted， and five items were added； after the second round of expert consultation， ten items were modified. The final version of the questionnaire included three dimensions （knowledge， attitudes， and practice）， 17 questionnaire factors， and 40 items. CONCLUSIONS The questionnaire has high reliability and scientific validity with relatively concentrated expert opinions. It is suitable for assessing the knowledge， attitudes， and practice status of patients receiving oral anticoagulant therapy.

Distribution and comparison of warfarin drug-gene polymorphism in Han children from Beijing area / 中国药房

OBJECTIVE To analyze the distribution characteristics of warfarin drug-gene polymorphism in Han children from Beijing area. METHODS Data of nine warfarin drug-gene loci about VKORC1 rs9923231， CYP2C9 rs1799853*2 and rs1057910*3， CYP4F2 rs2108622， APOE rs429358 and rs7412， ABCB1 rs1045642， EPHX1 rs1051740 and rs2234922 were collected from dept. of cardiovascular medicine， Children’s Hospital Affiliated to Capital Institute of Pediatrics from March 2019 to March 2023， and the population data reported in domestic and foreign literature were compared. RESULTS In Beijing area， the frequency of APOE rs429358 mutant genotype was higher in males （19.8%） than in females （13.5%）（P＜0.05）. VKORC1 rs9923231 was dominated by homozygous mutant genotype （83.3%）， which was consistent with children in Japan （82.2%）， and higher than that of predominantly Caucasian children in the UK， Sweden， the United States， and Germany （10.4%-18.3%）（P＜ 0.05）； CYP2C9 was dominated by *1/*1 type （91.9%）， which was consistent with children in Japan （94.6%）， and higher than that of predominantly Caucasian children in the UK， Sweden， the United States， and Germany （66.1%-73.4%）（P＜0.05）. The frequency of EPHX1 rs1051740 mutant genotype was higher in adults （78.5%） than in children （63.5%）（P＜0.05）. CONCLUSIONS More mutations of VKORC1 rs9923231 and ABCB1 rs1045642 are found in Han children from Beijing area. The distribution of warfarin drug-gene polymorphisms in Han children from Beijing area is different among different genders， as well as compared with other countries， and Chinese Han adults. Therefore， caution should be exercised when using the reported data.

Clinical Comprehensive Evaluation of Oral Anticoagulants Based on A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition) / 医药导报

Objective A comprehensive evaluation of oral anticoagulants(OACs)was conducted using the A Quick Guideline for Drug Evaluation and Selection in Chinese Medical Institutions(the Second Edition),to provide a reference for drug selection and clinical medication decisions in medical institutions.Methods Evaluation evidence was collected,and the drugs included in the evaluation were quantified on four dimensions of clinical properties(efficiency and safety),pharmaceutical properties,economy and others.Results All oral anticoagulants included in the evaluation had a score of 70 or higher in the comprehensive evaluation,while warfarin had the highest overall score.Clinical properties and pharmacologic properties were identified as the core attributes for drug selection evaluation.When considering only these factors,edoxaban received the highest score.Conclusion OACs are the preferred option for patients requiring long-term anticoagulation therapy.Various OACs offer distinct clinical advantages.Utilizing the Guidelines(Second Edition)for oral anticoagulant selection and evaluation can offer visual evidence for drug selection and promote the scientific,rational,and safe use of drugs in clinical management.

Validación al español de Colombia de la escala DASS (Duke Anticoagulation Satisfaction Scale) / Validation in Colombian Spanish of DASS (Duke Anticoagulation Satisfaction Scale)

Resumen Introducción: Evaluar la calidad de vida de los pacientes anticoagulados es importante; no existe en la actualidad una validación al español de la escala de satisfacción de anticoagulación de Duke (DASS). Objetivo: Realizar una validación lingüística y una estimación preliminar de las propiedades psicométricas en español colombiano de la escala de satisfacción DASS para evaluar la calidad de vida en pacientes anticoagulados con antagonistas de la vitamina K. Materiales y método: Estudio de validación de una escala cualitativa realizado en un hospital universitario de Bogotá, Colombia. La validación tuvo tres fases: traducción y adaptación cultural por un panel bilingüe; prueba piloto que incluye aplicación inicial, entrevista cognitiva con pacientes (n: 5) y revisión clínica por expertos (n: 10); valoración de la consistencia interna de la escala (n: 100). Conclusiones: Esta es la primera versión de la escala DASS publicada en español. El proceso de traducción y adaptación cultural resultó en una escala equivalente a su versión original. El análisis de consistencia interna mostró una escala altamente consistente, pero no redundante.

Abstract Introduction: Assessing the quality of life of anticoagulated patients is important; there is currently no Spanish validation of the Duke Anticoagulation Satisfaction Scale (DASS). Objective: To conduct a linguistic validation and preliminary psychometric properties estimation in Colombian Spanish of the DASS for assessing quality of life in patients anticoagulated with vitamin K antagonists. Materials and method: A validation study of a qualitative scale conducted in a private university hospital in Bogotá, Colombia. This validation had three phases: translation and cultural adaption by a bilingual panel; pilot test including initial application, cognitive interview with patients (n: 5), and clinical review by experts (n:10) and internal consistency assessment of the scale (n: 100). Results: The study yielded a version of DASS in Colombian Spanish that was technically and conceptually equivalent to the English version. The domains of limitations in patient activity, discomfort produced by anticoagulation, and psychological impact had a Cronbach's Alpha of 0.9. According to expert opinion, most questions had the right relevance (Aiken V coefficient: 0.67-0.87). Conclusion: This is the first version of the DASS published in Spanish. The translation and cultural adaptation process resulted in a scale equivalent to its original version. The internal consistency analysis showed a highly consistent but not redundant scale.

Comparing follow-up of patients with vitamin K antagonists in a health center: pre- and post-COVID-19 pandemic / Comparação do seguimento de doentes hipocoagulados com antagonistas da vitamina K numa unidade de saúde: pré e pós pandemia COVID-19

Introduction and objectives: During the COVID-19 pandemic, the follow-up of patients treated with vitamin K antagonists (VKAs) may have been affected. This study aims to compare how these patients were monitored pre- and post-COVID-19 pandemic and understand the impact of non-face-to-face appointments on their follow-up. Methods: We conducted a retrospective cohort study in a Portuguese Health Center. The study included patients treated with VKAs and followed at the Health Center for international normalized ratio (INR) monitoring between March 2019 and March 2021. Data collected: sex, age, type of VKA; INR; date of INR assessment, type of appointment (face-to-face or phone/e-mail). Rosendaal's method was used to calculate pre-COVID-19 and post-COVID-19 time in therapeutic range (TTR). Good TTR control was defined if values ≥ 70%. Results: 44 patients were included. The mean TTR in the pre-COVID-19 period was 64.55% (95% CI: 58.10 - 71.00%). The post-COVID-19 mean was slightly higher (+ 2.26%), 66.81% (95% CI: 59.66 - 73.97%), but the difference was not statistically significant (p = 0.576). The use of non-face-to-face appointments did not contribute to worsening post-pandemic TTR, show-ing no lower follow-up than during pre-pandemic period in which all contacts were face-to-face [CI (95%) -0.397 - 0.196 for a reference range -0.489 - 0.693]. Conclusions: The TTR value in both periods was similar and lower than the value defined for effective hypocoagulation. The use of non-face-to-face consultation in the post-COVID-19 period does not seem to have influenced the quality of hypocoagulation (AU).

Introdução e objetivos: Durante a pandemia COVID-19 o acompanhamento de doentes medicados com antagonistas da vitamina K (AVKs) pode ter sido afetado. Este estudo pretende comparar a forma como estes doentes foram monitorizados antes e depois da pandemia COVID-19 e compreender o impacto da consulta não presencial no seu seguimento. Métodos: Estudo de coorte retrospetivo num Centro de Saúde em Portugal. O estudo incluiu doentes tratados com AVKs e seguidos no Centro de Saúde para monitorização do International Normalized Ratio(INR) entre março de 2019 e março de 2021. Dados recolhidos: sexo, idade, tipo de AVK; INR; data da avaliação do INR, tipo de consulta (presencial ou por telefone/e-mail). Foi utilizado o método de interpolação linear de Rosendaal para calcular o tempo em intervalo terapêutico (TTR) pré- e pós-COVID-19. Foi definido um bom controle se valores de TTR ≥ 70%. Resultados: Foram incluídos 44 doentes. A média de TTR no período pré-COVID-19 foi de 64,55% (95% IC: 58,10 - 71,00%). A média pós-COVID-19 foi ligeiramente superior (+ 2,26%), 66,81% (95% IC: 59,66 - 73,97%), mas a diferença não foi estatisticamente significativa (p = 0,576). A utilização da consulta não presencial não contribuiu para o agravamento do TTR no período pós-pandemia, não mostrando um seguimento inferior ao do período pré-pandemia em que todos os contatos foram presenciais [IC (95%) -0,397 - 0,196 para um intervalo de referência -0,489 - 0,693]. Conclusões: O valor de TTR em ambos os períodos foi semelhante e inferior ao valor definido para hipocoagulação eficaz. A utilização da consulta não presencial no período pós-COVID-19 não parece ter influenciado a qualidade da hipocoagulação (AU).

Health Literacy, Patient Knowledge and Adherence to Oral Anticoagulation in Primary Care

Abstract Background Warfarin is the only oral anticoagulant available in the Brazilian public health system. Health knowledge and treatment are essential to achieving the desirable therapeutic effect. However, data on these aspects among primary care patients are still lacking. Objective To assess health literacy, patient knowledge, and adherence to oral anticoagulation with warfarin, as well as the medication regimen complexity in primary health units in the municipality of Divinópolis, Minas Gerais, Brazil. Methods This cross-sectional study included patients using warfarin from primary care settings. Sociodemographic and clinical data were collected from medical records. Short Assessment of Health Literacy for Portuguese-Speaking Adults (SAHLPA-18), Oral Anticoagulation Knowledge (OAK), adaptation of the Measure of Adherence to Treatment (MAT-adapted) to oral anticoagulation, and Medication Regimen Complexity Index (MRCI) were applied, and the time in therapeutic range (TTR) was calculated. Patients were stratified in two groups (TTR < 60% and TTR ≥ 60%) and compared using Fisher's exact test at a significance level of p < 0.050. Results Analysis included 162 patients (64.8 ± 12.7 years old, 55.6% women). Nonvalvular atrial fibrillation (26.5%) and venous thromboembolism (24.1%) were the main indications for warfarin, and 67.9%, 88.3%, and 16.7% of the patients had inadequate health literacy, insufficient knowledge regarding anticoagulant therapy, and non-adherence to warfarin therapy, respectively. There was no significant association of these parameters in relation to TTR. MRCI showed high pharmacotherapy complexity between the drug prescriptions. Conclusion This study showed alarming insufficient knowledge about warfarin therapy and low health literacy in primary care patients.

Practice and experience of clinical pharmacists participating in pharmaceutical care for patients after heart valve replacement / 药学实践与服务

Objective To explore the starting point of pharmaceutical care by clinical pharmacists for patients after heart valve replacement. Methods Combined with typical cases, the content, focus and effects of pharmaceutical care for patients after heart valve replacement were summarized. Results Clinical pharmacists provided pharmaceutical services such as anticoagulant care and warfarin dosage adjustment, infection monitoring and rational use and care of antibacterial, perioperative airway management, stress ulcer (SU) prevention and pharmaceutical care, and warfarin medication education for patients, which had promoted the rational use of drugs and improved the treatment results of patients. Conclusion Pharmaceutical care by clinical pharmacists could be helpful to improve the safety and efficacy of drug treatment for patients after heart valve replacement.

Efficacy and safety of percutaneous left atrial appendage occlusion for nonvalvular atrial fibrillation / 中国基层医药

Objective:To investigate the efficacy and safety of percutaneous left atrial appendage occlusion in the treatment of nonvalvular atrial fibrillation.Methods:Eighty-eight patients with percutaneous left nonvalvular atrial fibrillation who received treatment in The Second Hospital of Anhui Medical University from January 2019 to January 2021 were included in this study. These patients were divided into three groups according to different anticoagulant methods: group A (percutaneous left atrial appendage occlusion), group B (livaraban), and group C (warfarin). The incidence of stroke, the incidence of bleeding events, the incidence of adverse cardiovascular events, and live and kidney function and coagulation function after 3 months of treatment were compared among the three groups.Results:There were no significant differences in the incidence of stroke and adverse cardiovascular events among the three groups ( P > 0.05). The incidence of bleeding events in groups A, B, and C was 9.3% (3/32), 15.0% (6/40), and 31.2% (5/16), respectively. There was a significant difference in the incidence of bleeding events among the three groups ( χ2 = 8.07, P = 0.001). After 3 months of treatment, there were no significant differences in prothrombin time, fibrinogen, prothrombin time-international normalized ratio, alanine aminotransferase, aspartate transaminase, and creatinine clearance among the three groups (all P > 0.05). Conclusion:Percutaneous left atrial appendage occlusion, warfarin, and rivaroxaban can prevent stroke in patients with nonvalvular atrial fibrillation. Percutaneous left atrial appendage occlusion is safer and more feasible than warfarin and rivaroxaban alone in the treatment of nonvalvular atrial fibrillation.

Predictive value of early international normalized ratio for Warfarin overanticoagulation in elderly patients with atrial fibrillation / 中华老年医学杂志

Objective:To investigate the relationship between early international normalized ratio(INR)and overanticoagulation in elderly patients with atrial fibrillation(AF)treated with Warfarin, and to evaluate its clinical value in predicting overanticoagulation.Methods:A total of 470 elderly patients with AF treated with Warfarin for anticoagulation were enrolled retrospectively.INR was detected in the morning of the next day after 3 days and 7 days of Warfarin treatment.According to whether INR was greater than 3.0 after 7 days of Warfarin treatment, the patients were divided into over-anticoagulation group(n=107)and non-over-anticoagulation group(n=363). The general clinical data of the two groups were analyzed.The receiver operating characteristic curve(ROC)was used to evaluate the value of 3-day INR(early INR)level in predicting overanticoagulation.Logistic regression was used to analyze the factors related to overanticoagulation in elderly AF patients receiving Warfarin treatment.Results:The age, initial warfarin dose, early INR and serum aspartate transferase level in the over-anticoagulation group were higher than those in the non-over-anticoagulation group( P<0.05 for all). The proportions of patients with initial Warfarin dose≥2.5 mg, age≥70 years old, body weight≤65 kg, valvular atrial fibrillation, hypoproteinemia, abnormal liver function, and combined use of antibiotics were higher in the over-anticoagulation group than those in the non-over-anticoagulation group( P<0.05 for all). The body weight, serum albumin level and the proportion of diabetes mellitus in the over-anticoagulation group were lower than those in the non-over-anticoagulation group( P<0.05). ROC curve showed that the area under the curve(AUC)of early INR in predicting over-anticoagulation was 0.927(95% CI: 0.900-0.949, P<0.0001), the sensitivity was 82.86% and the specificity was 88.43%, the optimal cutoff value for predicting overanticoagulation was INR≥1.66.Multiple Logistic regression analysis showed that early INR level≥1.66( OR=33.871, P<0.001), initial warfarin dose≥2.5 mg( OR=17.062, P=0.011), body weight≤65 kg( OR=2.824, P=0.002), age≥70 years old( OR=2.678, P=0.003), and abnormal liver function( OR=2.091, P=0.022)were related factors for over-anticoagulation in elderly patients with atrial fibrillation. Conclusions:Early INR level is closely related to overuse of anticoagulation in elderly AF patients receiving Warfarin treatment, which can be regarded as a predictor of overuse of anticoagulation.Early INR level in elderly AF patients receiving warfarin treatment should be monitored to reduce the incidence of anticoagulant overuse.

Pharmaceutical care of patients with antithrombotic therapy after transjugular intrahepatic portal shunt / 中国临床药理学与治疗学

AIM: To explore the role of clinical pharmacist in the treatment of patients with transjugular intrahepatic portosystemic shunt. METHODS: Clinical pharmacist participated in the treatment of a patient with repeated oral bleeding after transjugular intrahepatic portal shunt followed treatment with multiple antithrombotic drugs, which assisted the physician to diagnose and adjust the antithrombotic treatment plan as well as provided the patient with whole-process pharmaceutical care and online management. RESULTS: Based on the inquiry about the patient's past and current medical history and medication consumption, the pharmacist considered that there was weak correlation between oral hemorrhage and antithrombotic drugs and advised for dentist inspection. Thereafter, the patient was diagnosed with chronic gingivitis. The dosage of warfarin was adjusted, and the pharmacists managed it online after discharge to achieve stable INR of the patient. In the later online follow-up, an abnormal increase of INR was encountered, By asking about the history of medication, it was considered that the increase in INR was related to taking amoxicillin capsules. Therefore, the pharmacist suggested to stop amoxicillin capsule and to gradually adjust the dose of warfarin to the original level to improve the treatment. CONCLUSION: The involvement of clinical pharmacists in clinical treatment facilitates comprehensive pharmaceutical care of patients, which plays a positive role in the efficacy and safety of medication therapy.

Efficacy and Safety of Rivaroxaban and Dabigatran in Anticoagulant Therapy for Patients with Non-valvular Atrial Fibrillation combined with Diabetes Mellitus / 医药导报

Objective To investigate the efficacy and safety of new oral anticoagulants(NOACs)rivaroxaban and dabigatran versus warfarin in the treatment of the patients with non-valvular atrial fibrillation combined with diabetes mellitus.Methods A retrospective study was performed on 119 cases of patients with non-valvular atrial fibrillation combined with diabetes mellitus from outpatient and inpatient of the Ninth People's Hospital of Suzhou City from Jan 2019 to June 2021.According to the use of anticoagulants,patients were divided into rivaroxaban 10 mg group(Group A,n=25),rivaroxaban 15 mg group(Group B,n=30),dabigatran group(Group C,n=29),and warfarin group(Group D,n=35).All patients were treated continuously for at least 6 months.The incidence of embolism and bleeding events,the changes of coagulation indicator,blood glucose,liver and kidney function indexes were compared before and after treatment among the four groups.Results Thromboembolic events:1 cases(4.00%)of stoke or thromboembolic events occurred in Group A;2 cases(6.67%)occurred in Group B;2 cases(6.90%)occurred in Group C,and 5 cases(14.28%)occurred in Group D.Bleeding events:1 cases(4.00%)of bleeding events occurred in Group A;1 cases(3.33%)occurred in Group B;2 cases(6.90%)occurred in Group C,and 8 cases(22.85%)occurred in Group D.There was no statistically significant difference among the four groups of stoke or thromboembolic events(P>0.05).The incidence of bleeding events in Group A and B were both statistically lower than Group D(P<0.05),and the risk of bleeding events of Group C was similar to Group D(P>0.05)and there was also no statistically significant difference among Group A,B and C(P>0.05).The activated partial thromboplastin time(APTT)of all patients was significantly prolonged after treatment compared with before treatment(P<0.05),but none of them exceeded the upper limit of the normal value by 2 times.The APTT and international normalized ratio(INR)values of Group A and B,INR values of Group C were all statistically better than those of Group D(P<0.05)after the treatment.There were no statistically significant difference in the comparison of blood glucose,liver and kidney function index as well(P>0.05).Conclusion The new oral anticoagulants rivaroxaban and dabigatran showed similar effects in prevention of stroke or thromboembolic events,but better safety profiles with lower risks of bleeding events compared to warfarin in patients with non-valvular atrial fibrillation combined with diabetes mellitus.Dabigatran is comparable in efficacy and safety when compared with rivaroxaban and deserves to be promoted for clinical use.

Antitrombóticos en las prótesis valvulares biológicas: ¿cuál es el mejor camino a seguir? / Antithrombotics in biological valve prostheses: what is the best way forward? / Antitrombóticos em próteses de válvulas biológicas: qual é o melhor caminho a seguir?

La enfermedad valvular cardíaca es una condición muy frecuente en la población general y un porcentaje considerable de estos pacientes requieren un tratamiento intervencionista sobre su valvulopatía para lograr atenuar su evolución natural. En este contexto, en la actualidad ha aumentado el uso de las prótesis valvulares biológicas para su tratamiento y, con ello, surge el dilema del manejo antitrombótico en estos pacientes en términos de prevención de tromboembolias y eventos hemorrágicos. ¿Cuál es el fármaco más efectivo y seguro en el período posoperatorio temprano? ¿Qué antitrombóticos podemos utilizar en el período posoperatorio tardío? ¿Qué estrategia seguimos cuando el paciente presenta otras indicaciones de anticoagulación? El objetivo de esta revisión es valorar la evidencia actual respecto al tratamiento antitrombótico en pacientes portadores de prótesis valvulares biológicas con y sin indicaciones adicionales de anticoagulación.

Heart valve disease is a very common condition in the general population and a considerable percentage of these patients require interventional treatment for their valve disease to mitigate its natural evolution. In this context, the use of biological prosthetic valves for their treatment has now increased, and with this, the dilemma of antithrombotic management in these patients arises, in terms of prevention of thromboembolism and hemorrhagic events. What is the most effective and safe drug in the early postoperative period? What antithrombotics can we use in the late postoperative period? What strategy do we follow when the patient presents other indications for anticoagulation? The objective of this review is to assess the current evidence regarding antithrombotic treatment in patients with biological prosthetic valves with and without additional indications for anticoagulation.

A valvopatia é uma condição muito comum na população geral e uma porcentagem considerável desses pacientes necessita de tratamento intervencionista para sua valvopatia para amenizar sua evolução natural. Nesse contexto, o uso de próteses valvares biológicas para seu tratamento tem aumentado, e com isso surge o dilema do manejo antitrombótico nesses pacientes em termos de prevenção de tromboembolismo e eventos hemorrágicos. Qual é o fármaco mais eficaz e seguro no pós-operatório imediato? Que antitrombóticos podemos usar no pós-operatório tardio? Que estratégia seguimos quando o paciente apresenta outras indicações de anticoagulação? O objetivo desta revisão é avaliar as evidências atuais sobre o tratamento antitrombótico em pacientes com próteses valvares biológicas com e sem indicações adicionais de anticoagulação.

Caracterização e avaliação do paciente anticoagulado com varfarina em relação à complexidade da farmacoterapia / Characterization and evaluation of patients anticoagulated with warfarin in relation to the complexity of pharmacotherapy

A realização de diagnóstico e tratamento das arritmias sustentadas fazem parte da rotina clínica, sendo uma das arritmias mais frequentes a Fibrilação Atrial (FA). Para prevenção de eventos tromboembólicos em pacientes com FA, recomendase a anticoagulação oral, destacando-se a varfarina. Apesar da importância, esse medicamento possui estreita margem terapêutica, o que faz com que pequenas mudanças no tratamento gerem risco de eventos trombóticos ou hemorrágicos. Dentre essas mudanças, destaca-se a adesão aos demais medicamentos em uso, alteração do uso desses medicamentos por prescritores e automedicação. Várias são as interações entre varfarina e demais medicamentos de uso contínuo, acreditando-se que a complexidade da prescrição pode interferir nos desfechos clínicos da terapia anticoagulante. O objetivo do estudo foi caracterizar pacientes acompanhados em um ambulatório de anticoagulação em relação ao Índice de Complexidade da Farmacoterapia. Para identificação da complexidade da farmacoterapia, considerou-se as prescrições dos demais medicamentos em uso, prescritas por médicos da atenção primária em saúde. Utilizouse o instrumento Medication Regimen Complexity Index (MRCI). A complexidade, compreendida como a forma de administração, posologia e forma farmacêutica, fatores que interferem na adesão à terapia anticoagulante, foi subdividida em três níveis: baixa complexidade, moderada e alta, conforme indicado pela literatura. A análise da complexidade foi realizada por dois pesquisadores de forma independente, sendo considerados os critérios conforme orientação do MRCI. Trata-se de um estudo descritivo realizado em duas clínicas de anticoagulação, localizadas em Minas Gerais. Durante a pesquisa, pacientes foram acompanhados em dois ambulatórios de anticoagulação do Brasil, em uso de varfarina, foram convidados a participarem de um ensaio clínico entre dezembro de 2018 e fevereiro de 2019, sendo que posteriormente foi realizado um recorte para o presente estudo. Um total de 93 pacientes foram incluídos no estudo, sendo a média de idade de 63 anos e a maioria do sexo feminino (68,8%). A fibrilação atrial foi a indicação da ACO mais predominante (92,5%). A média do número de medicamentos utilizados foi de 7,0. A maioria dos pacientes com farmacoterapia classificada como alta (38, 6,5%) e média complexidade (24, 80,7%) apresentou TTR inadequado. O presente estudo permitiu identificar que há um predomínio de pacientes com alta complexidade da farmacoterapia, o que pode indicar necessidades de cuidados adicionais em relação ao tratamento anticoagulante. Para tanto, em casos de pacientes com controle inadequado da anticoagulação oral, recomenda-se que aspectos da complexidade da farmacoterapia sejam incorporados na abordagem educacional.

Diagnosis and treatment of sustained arrhythmias are part of the clinical routine, with one of the most frequent arrhythmias being Atrial Fibrillation (AF). To prevent thromboembolic events in patients with AF, oral anticoagulation is recommended, particularly warfarin. Despite its importance, this medication has a narrow therapeutic range, which means that small changes in treatment generate a risk of thrombotic or hemorrhagic events. Among these changes, adherence to other medications in use, changes in the use of these medications by prescribers and self-medication stand out. There are several interactions between warfarin and other medications for continuous use, with the belief that the complexity of the prescription may interfere with the clinical outcomes of anticoagulant therapy. The objective of the study was to characterize patients followed in an anticoagulation outpatient clinic in relation to the Pharmacotherapy Complexity Index. To identify the complexity of pharmacotherapy, prescriptions for other medications in use, prescribed by primary health care doctors, were considered. The Medication Regimen Complexity Index (MRCI) instrument was used. Complexity, understood as the form of administration, dosage and pharmaceutical form, factors that interfere with adherence to anticoagulant therapy, was subdivided into three complexity levels: low, moderate and high, as indicated in the literature. The complexity analysis was carried out by two researchers independently, considering the criteria as per MRCI guidance. This is a descriptive study carried out in two anticoagulation clinics, located in Minas Gerais. During the research, patients were monitored in two anticoagulation clinics in Brazil, using warfarin, and were invited to participate in a clinical trial between December 2018 and February 2019, and a selection was subsequently made for the present study. A total of 93 patients were included in the study, the average age was 63 years and the majority were female (68.8%). Atrial fibrillation was the most predominant OAC indication (92.5%). The average number of medications used was 7.0. The majority of patients with pharmacotherapy classified as high (38, 6.5%) and medium complexity (24, 80.7%) presented inadequate TTR. The present study identified that there is a predominance of patients with high complexity of pharmacotherapy, which may indicate the need for additional care in relation to anticoagulant treatment. Therefore, in cases of patients with inadequate control of oral anticoagulation, it is recommended that aspects of the complexity of pharmacotherapy be incorporated into the educational approach.

Construção e Validação do Protocolo EmpoderACO Direcionado a Pacientes em Anticoagulação Oral com Varfarina / Construction and Validation of a Protocol Targeting Patients on Oral Anticoagulation with Warfarin

Resumo Fundamento A varfarina é um anticoagulante oral útil para prevenção de tromboembolismo, embora seja considerado fármaco de alto risco de causar eventos adversos. Considerando os desafios práticos no controle da anticoagulação oral, os pacientes poderiam se beneficiar de estratégias educacionais que visem mudança de comportamento, participação ativa no autocuidado e adesão à farmacoterapia. Objetivo Construir e validar o protocolo EmpoderACO para mudança de comportamento em pacientes em uso de varfarina. Métodos As etapas metodológicas foram: definição de conceitos e domínios do autocuidado, identificação dos objetivos, construção e seleção dos itens, avaliação da validade de conteúdo e pré-teste na população alvo. Resultados Relevância, adequação, clareza e confiabilidade interna dos itens do instrumento foram avaliadas por comitê de juízes multiprofissional pela plataforma web E-surv, obtendo-se média de concordância ≥0,91. A compreensão do instrumento pela população-alvo teve clareza adequada com média de 0,96. Conclusão O EmpoderACO poderá contribuir para qualificar o processo de comunicação entre profissionais e pacientes, melhorar a adesão ao tratamento e os resultados clínicos, podendo ser replicado nos serviços de saúde.

Abstract Background Warfarin is an oral anticoagulant that is very useful in preventing thromboembolism, though it is considered a drug with a high risk of causing adverse events. Considering the practical challenges in controlling oral anticoagulation, the patients on warfarin could benefit from educational strategies aimed at behavioral changes, active participation in self-care, and adherence to drug therapy. Objective The aim was to construct and validate the EmpoderACO protocol for behavioral changes in warfarin patients. Methods The methodological steps were: definition of concepts and domains of self-care, identification of objectives, construction and selection of items, assessment of content validity, and pre-test in the target population. Results Relevance, adequacy, clarity, and internal reliability of the instrument's items were assessed by a multidisciplinary judges committee (JC) through the E-surv web platform, obtaining an average agreement of ≥0.91. The understanding of the instrument measured by the target population revealed adequate clarity with a coefficient average of 0.96. Conclusion EmpoderACO can aid in qualifying the communication process between medical professionals and patients, as well as in improving adherence to both treatment and clinical outcomes, and can be replicated in healthcare settings.

Development and validation of a mobile application based on a machine learning model to aid in predicting dosage of vitamin K antagonists among Indian patients post mechanical heart valve replacement

Patients who undergo heart valve replacements with mechanical valves need to take Vitamin K Antagonists (VKA) drugs (Warfarin, Nicoumalone) which has got a very narrow therapeutic range and needs very close monitoring using PT-INR. Accessibility to physicians to titrate drugs doses is a major problem in low-middle income countries (LMIC) like India. Our work was aimed at predicting the maintenance dosage of these drugs, using the de-identified medical data collected from patients attending an INR Clinic in South India. We used artificial intelligence (AI) - machine learning to develop the algorithm. A Support Vector Machine (SVM) regression model was built to predict the maintenance dosage of warfarin, who have stable INR values between 2.0 and 4.0. We developed a simple user friendly android mobile application for patients to use the algorithm to predict the doses. The algorithm generated drug doses in 1100 patients were compared to cardiologist prescribed doses and found to have an excellent correlation.

Manejo del paciente anticoagulado en una cirugía dental / Management of the anticoagulated patient in dental surgery / Gerenciamento do paciente anticoagulado em cirurgia odontológica

Introducción: una adecuada hemostasia es crucial para el éxito del tratamiento odontológico invasivo, ya que los problemas de sangrado pueden dar lugar a complicaciones asociadas a una importante morbimortalidad. El tratamiento odontológico de pacientes que tienden a un mayor riesgo de sangrado debido al uso de fármacos anticoagulantes plantea un desafío en la práctica diaria de los profesionales de la odontología. El conocimiento adecuado de los mecanismos subyacentes a la hemostasia y el manejo optimizado de estos pacientes son, por lo tanto, cuestiones muy importantes. Se realiza un estudio de los fármacos anticoagulantes actualmente disponibles en el mercado, evaluando los riesgos y beneficios de suspender dicho fármaco previo a un tratamiento odontológico invasivo. Además, se hace una revisión de los protocolos de manejo actuales que se utilizan en estos pacientes. Material y métodos: se realizó una búsqueda bibliográfica en las bases de datos Epistemonikos y Medline/PubMed; en el portal Timbó y en la biblioteca virtual Scielo. Abarcando todos los estudios publicados en los últimos 15 años en inglés y español. Se encontraron 30 artículos, se seleccionaron 15 en primera instancia para finalizar con 11 artículos. En dicha selección el filtro fue que los demás artículos se referían a otros anticoagulantes que no eran parte de este trabajo. Resultados: se han desarrollado múltiples protocolos de manejo, aunque en todos los casos se requiere una historia clínica completa, junto con pruebas hemostáticas complementarias para minimizar los riesgos derivados del tratamiento odontológico. Discusión: muchos autores consideran que la medicación de los pacientes indicada para el tratamiento de una enfermedad de base no debe ser alterada o suspendida a menos que así lo indique el médico prescriptor. Se ha demostrado que las medidas hemostáticas locales son suficientes para controlar los posibles problemas de sangrado derivados del tratamiento dental.

Introduction: Adequate hemostasis is crucial for the success of invasive dental treatment, since bleeding problems can lead to complications associated with significant morbidity and mortality. The dental treatment of patients who are prone to an increased risk of bleeding due to the use of anticoagulant drugs poses a challenge in the daily practice of dental professionals. Adequate knowledge of the mechanisms underlying hemostasis and optimized management of these patients are therefore very important issues. A review is made of the anticoagulant drugs currently available on the market, evaluating the risks and benefits of suspending such a drug prior to invasive dental treatment. In addition, a review is made of the current management protocols used in these patients. Material and methods: A bibliographic search was carried out in the Epistemonikos and Medline/PubMed databases; in the Timbo portal and in the Scielo virtual library. All the studies published in the last 15 years in English and Spanish were included. Thirty articles were found, 15 were selected in the first instance to end up with 11 articles. In this selection, the filter was that the other articles referred to other anticoagulants that were not part of this work. Results: multiple management protocols have been developed, although in all cases a complete clinical history is required, together with complementary hemostatic tests to minimize the risks derived from dental treatment. Discussion: many authors consider that the patient's medication indicated for the treatment of an underlying disease should not be altered or suspended unless so indicated by the prescribing physician. It has been shown that local hemostatic measures are sufficient to control possible bleeding problems derived from dental treatment.

Introdução: A hemostasia adequada é crucial para o sucesso do tratamento dentário invasivo, pois problemas de sangramento podem levar a complicações associadas a uma morbidade e mortalidade significativas. O tratamento odontológico de pacientes que são propensos a um risco maior de sangramento devido ao uso de drogas anticoagulantes representa um desafio na prática diária dos profissionais da odontologia. O conhecimento adequado dos mecanismos subjacentes à hemostasia e o gerenciamento otimizado desses pacientes são, portanto, questões muito importantes. É realizada uma revisão dos anticoagulantes atualmente disponíveis no mercado, avaliando os riscos e benefícios de descontinuar tal medicamento antes do tratamento dentário invasivo. Além disso, é feita uma revisão dos protocolos de gerenciamento atuais usados nesses pacientes. Material e métodos: Foi realizada uma pesquisa bibliográfica nas bases de dados Epistemonikos e Medline/PubMed; no portal Timbo e na biblioteca virtual Scielo. Todos os estudos publicados nos últimos 15 anos, em inglês e espanhol, foram incluídos. Trinta artigos foram encontrados, 15 foram selecionados em primeira instância para acabar com 11 artigos. Nesta seleção, o filtro foi que os outros artigos se referiam a outros anticoagulantes que não faziam parte deste trabalho. Resultados: foram desenvolvidos múltiplos protocolos de gerenciamento, embora em todos os casos seja necessário um histórico clínico completo, juntamente com testes hemostáticos complementares para minimizar os riscos derivados do tratamento odontológico. Discussão: muitos autores consideram que a medicação os pacientes indicada para o tratamento de uma doença subjacente não deve ser alterada ou descontinuada, a menos que o médico que a prescreve dê instruções nesse sentido. Medidas hemostáticas locais demonstraram ser suficientes para controlar potenciais problemas de sangramento resultantes do tratamento odontológico.