Meta-analysis of efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery / 中国药房

OBJECTIVE To evaluate the clinical efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and VIP， randomized controlled trials （RCTs） and cohort studies about aspirin （trial group） versus other anticoagulants （control group） were collected during the inception and June 1st， 2023. After literature screening， data extraction and quality evaluation， the meta-analysis was conducted by using RevMan 5.4 software. RESULTS A total of 22 studies were included， involving 9 RCTs and 13 cohort studies. RCT results showed that the incidences of deep vein thrombosis （DVT） [RR＝1.81， 95%CI（1.36， 2.40）， P＜0.000 1] and postoperative pulmonary embolism （PE） [RR＝1.55， 95%CI（1.01， 2.40）， P＝0.05] in trial group were significantly higher than control group. There was no statistically significant difference in the incidences of postoperative massive bleeding， postoperative surgical site infection， all-cause death， or any bleeding after surgery between 2 groups. In the cohort study， the incidence of any bleeding in trial group was significantly lower than control group [RR＝0.71，95%CI （0.64， 0.79）， P＜0.000 1]， while the differences in other indicators were not statistically significant （P＞0.05）. The results of subgroup analysis based on different anticoagulants showed that in RCT， the incidences of DVT and PE after surgery in patients using low-molecular-weight heparin （LMWH） were significantly lower than using aspirin （P＜0.05）； in the cohort study， the incidences of DVT and PE after surgery were significantly lower in patients using direct oral anticoagulants （DOAC） than using aspirin （P＜0.05）. There was no statistically significant difference in the incidence of major bleeding between patients using aspirin and using DOAC and LWMH （P＞0.05） in both RCT and cohort study. CONCLUSIONS Aspirin is equally safe as other anticoagulants for the prevention of thromboembolism after orthopedic surgery， but its efficacy may not be as good as other anticoagulants. After orthopedic surgery， other anticoagulants should be preferred to prevent venous thromboembolism， and aspirin should be carefully considered.

Manejo odontológico del paciente en tratamiento de anticoagulante oral sometido a cirugía oral: una revisión narrativa / Stomatological management of anticoagulated patients undergoing oral surgery: a narrative review

Resumen Los pacientes que se encuentran bajo tratamiento de anticoagulantes orales, presentan alteraciones en distintas etapas de la hemostasia, lo que conlleva a tener implicancias y consideraciones médico/quirúrgicas durante su atención. En la actualidad, no existe un consenso en relación con el manejo odontológico de estos pacientes que serán sometidos a procedimientos quirúrgicos, llevando a protocolos clínicos que siguen diversas posturas, como la de disminuir la ingesta farmacológica del anticoagulante, sustituir con heparina y la de mantener el tratamiento bajo control. Objetivo Establecer el manejo estomatológico del paciente que se encuentra en tratamiento de anticoagulante oral mediante una revisión profunda de la literatura Materiales y método Se realizó una búsqueda de revisión bibliográfica manualmente de artículos indexados a las bases de datos de PUBMED y EBSCO que correspondiesen a las palabras "cirugía bucal", "anticoagulantes", "atención dental" y "hemorragia oral". En cuanto a los criterios de inclusión, se consideraron revisiones bibliográficas, estudios observacionales, ensayos clínicos, guías, revisiones sistemáticas y metaanálisis publicados entre noviembre de 2005 y 2022, en idiomas inglés o español. Conclusiones Existen múltiples protocolos para la atención del paciente anticoagulado que será sometido bajo procedimiento de cirugía oral menor. Es importante considerar el anticoagulante utilizado, motivo, control de este, el procedimiento a realizar en el paciente y medidas hemostáticas tanto intra como postoperatorias por realizar, tras analizar lo anterior, se advierte que disminuir la ingesta del fármaco para realizar el procedimiento, puede ser más perjudicial al paciente como al clínico, por lo tanto se sugiere mantener el tratamiento antitrombótico y realizar un correcto manejo médico/quirúrgico.

Abstract Patients undertaking oral anticoagulant treatment may experience alterations in different stages of hemostasis, which lead to medical/surgical implications and considerations during their care. Currently, there is no consensus regarding the dental management of these patients, as they go through surgical procedures. This leads to clinical protocols that follow numerous approaches, such as reducing the pharmacological intake of the anticoagulant, replacing it with heparin, and maintaining the controlled treatment. Objective: To establish the stomatological management of the patient undergoing oral anticoagulant treatment through an in depth review of the literature. Materials and Method: A manual bibliographic review search of articles indexed to the PUBMED and EBSCO databases corresponding to the words "oral surgery", "oral bleeding", "anticoagulants" and "dental management" was performed. Regarding the inclusion criteria: bibliographic reviews, observational studies, clinical trials, guidelines, systematic reviews, and meta-analyses published between November 2005 and 2022, in English or Spanish, were considered. Conclusion: There are multiple protocols for the care of the anticoagulated patient who will undergo a minor oral surgery procedure. It is important to reflect on the anticoagulant used, the reason for it, its supervision, the surgical procedure that will be undertaken by the patient, and both intraoperative and postoperative hemostatic measures to be implemented. After analyzing the above, it is noted that reducing the intake of the drug to perform the surgical procedure may be harmful to the patient and to the clinician, therefore it is suggested to maintain the antithrombotic treatment and carry out a correct medical/surgical management.

Manejo perioperatorio de medicación anticoagulante y antiagregante antiplaquetaria en radiología intervencionista / Perioperative management of anticoagulants and antiplatelets agents in interventional radiology

Resumen El número de personas en tratamiento con fármacos anticoagulantes o antiplaquetarios está en crecimiento constante debido al aumento de la supervivencia de los pacientes con fibrilación auricular, válvulas cardiacas mecánicas o que han sufrido un evento isquémico o trombótico agudo. Cuando estos pacientes necesitan un procedimiento radiológico intervencionista que acarrea riesgo de sangrado, es necesario analizar el riesgo trombótico del paciente al interrumpir la medicación frente al riesgo hemorrágico del procedimiento para tomar la decisión más adecuada en cada caso. Por tanto, es una decisión individualizada y supone un desafío para los/as radiólogos/as que realicen estas técnicas. Nuestro objetivo en esta revisión es mostrar las recomendaciones actuales sobre el manejo perioperatorio de la medicación anticoagulante y antiplaquetaria, adaptada al intervencionismo radiológico.

Abstract The number of people treated with anticoagulant or antiplatelet agents is constantly growing due to the increased survival of patients with atrial fibrillation, mechanical cardiac valves or who have suffered an acute thrombotic or ischemic event. When these patients need an interventional radiological procedure that carries a risk of bleeding, it is necessary to analyze the thrombotic risk of the patient when interrupting the medication against the hemorrhagic risk of the procedure, to make the most appropriate decision in each case. Therefore, it is an individualized decision, and it is a challenge for radiologists who perform these techniques. Our goal in this review is to update the current recommendations on the perioperative management of anticoagulant and antiplatelet agents, adapted to the radiological interventionism.

Outcomes of recurrent stroke in patients with atrial fibrillation according to presumed etiology / Desfecho de AVC recorrente em pacientes com fibrilação atrial de acordo com etiologia presumida

Abstract Background Atrial fibrillation (AF) is a potent risk factor for stroke. The presence of competing etiologies can modify disease outcomes and demand different treatment strategies. Objective The primary purpose of the study was to examine the differences in outcomes for patients with AF admitted with a recurrent stroke, stratified according to the presumed etiology of the stroke. Methods We analyzed AF patients admitted for a recurrent ischemic stroke in an academic comprehensive stroke center. Recurrent strokes were categorized as "Cardioembolic", meaning AF without any competing mechanism, versus "Undetermined" etiology due to competing mechanisms. We used logistic regression to test the association between recurrent stroke etiology and favorable outcome (discharge home), after accounting for important covariates. Results We included 230 patients, with a mean age 76.9 (SD ± 11.3), 52.2% male, median National Institute of Health Stroke Scale (NIHSS) score of 7 (IQR 2-16). Patients with cardioembolic stroke (65.2%) had higher median NIHSS 8.5 (3-18) versus 3 (1-8) and were more likely to be treated with reperfusion therapies. The favorable outcome was reached by 64 patients (27.8%), and in-hospital mortality was 15.2% overall. After adjustment, there was no difference in outcome between patients with cardioembolic versus undetermined stroke etiology (odds ratio for discharge home: 1.41; 95% CI: 0.65-3.15). Conclusions In this single-center sample of AF patients with history of stroke, there was no difference in discharge outcomes between those with cardioembolic and those with undetermined stroke etiology. This question warrants examination in larger samples to better understand the importance of the stroke mechanism and secondary prophylaxis.

Resumo Antecedentes Fibrilação atrial (FA) é um fator de risco importante para AVC. A presença de mecanismos concorrentes para o AVC pode modificar o desfecho e demandar estratégias de tratamento diferentes. Objetivo O objetivo primário do estudo foi examinar diferenças no desfecho de pacientes com FA admitidos por um AVC recorrente, sendo estratificados de acordo com a etiologia presumida do AVC. Métodos Nós analisamos pacientes com FA admitidos por conta de AVC recorrente em um centro acadêmico terciário de AVC. Os casos de AVC recorrentes foram classificados como "Cardioembólicos", sendo FA sem outros mecanismos alternativos, versus aqueles de etiologia "Indeterminada" por conta de mecanismos concorrentes. Foi usada regressão logística para testar a associação entre a etiologia do AVC recorrente e desfecho favorável (alta direto para casa) após controle para covariáveis importantes. Resultados Nós incluímos 230 pacientes, com uma idade média 76,9 anos (DP ± 11.3), 52.2% homens, com um escore mediano do National Institute of Health Stroke Scale (NIHSS) de 7 (IIQ 2-16). Pacientes com AVC cardioembólicos (65,2%) tiveram um escore de NIHSS mediano mais alto 8,5 (3-18) versus 3 (1-8), e com maior chance de tratamento com terapias de reperfusão. O desfecho favorável ocorreu em 64 pacientes (27,8%) e a mortalidade institucional foi de 15,2% no total. Após ajustes, não encontramos diferença no desfecho entre pacientes com AVC cardioembólico versus AVC de etiologia indeterminada (odds ratio para alta para casa: 1,41; 95% IC: 0,65-3,15). Conclusões Nessa amostra de pacientes com FA e história de AVC recorrente de centro único, não houve diferença no desfecho de alta entre aqueles com AVC cardioembólico e aqueles com etiologia indeterminada. Essa questão deve ser examinada em amostras maiores para melhor compreender a importância do mecanismo do AVC e a profilaxia secundária.

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.

Perspectiva neurológica en la elección del anticoagulante oral directo para la prevención del accidente cerebrovascular en fibrilación auricular / Neurological perspective in the choice of direct oral an ticoagulants for prevention of stroke in atrial fibrillation

Resumen La fibrilación auricular no valvular (FA) es la arritmia con potencial embolígeno más prevalente y una de las principales y crecientes causas de accidente cerebrovas cular isquémico (ACVi). El principal objetivo del uso de la anticoagulación en pacientes con FA es la prevención del ACVi. Hasta hace poco tiempo, la anticoagulación con antagonistas de la vitamina K (AVKs) era la única opción disponible. Los anticoagulantes orales directos (DOACs) como el inhibidor directo de la trombina, dabigatrán, o los inhibidores directos del factor Xa, rivaroxabán, apixa bán y edoxabán, tienen un perfil de efectividad/seguridad más favorable en comparación con los AVKs. No existen estudios que comparen la efectividad de los DOACs entre sí. La elección del DOAC depende de múltiples factores específicos del paciente, preferencias del médico, costos y accesibilidad. Entre 1-2% de los pacientes correctamente tratados con un DOAC intercurre con un ACVi cada año. La posibilidad de contar con un agente reversor debería ser tenida en cuenta al momento de la elección del DOAC, especialmente por el riesgo residual de ocurrencia de ACVi. En la actualidad, en nuestro país solo el dabigatrán cuenta con un agente reversor disponible y lo convierte en el único DOAC que no contraindica el uso de trombolisis intraveno sa con rtPA. Esta situación debería ser considerada en el momento de la elección del DOAC para la prevención de eventos tromboembólicos en pacientes con FA.

Abstract Non-valvular atrial fibrillation (AF) is the most preva lent arrhythmia with high embolic potential, and one of the main and growing causes of stroke. The main objec tive of anticoagulation in patients with AF is prevention of stroke. Until recently, anticoagulation with vitamin K antagonists (VKAs) was the only available option. Direct oral anticoagulants (DOACs), such as the direct thrombin inhibitor dabigatran, or the direct factor Xa inhibitors rivaroxaban, apixaban, and edoxaban, have a more favor able effectiveness/safety profile compared to VKAs. There are no studies comparing the efficacy of DOACs with each other. The choice of a DOAC arose from patient car achterictis, physician preferences, cost, and accessibility. Between 1-2% of patients correctly treated with a DOAC experience a stroke each year. The possibility of having a reversal agent should be taken into account when choos ing a DOAC, especially due to the residual risk of stroke occurrences even under DOACs. Currently, in our country only dabigatran has a reversing agent available, making it the only DOAC that does not contraindicate the use of intravenous thrombolysis. This should be taken into account when choosing the DOAC for the prevention of thromboembolic events in patients with AF.

Anticoagulación en enfermedad renal crónica G4-5 en una red de hospitales de Bogotá

Contexto: la anticoagulación en pacientes con enfermedad renal crónica es un reto terapéutico debido a que la evidencia médica es escasa y los beneficios son discutibles, además, el riesgo de sangrado en estos pacientes es mayor. Objetivo: describir los pacientes con enfermedad renal G4-5 que recibieron terapia anticoagulante oral durante por lo menos tres meses en la Subred Centro Oriente de Bogotá. Metodología: estudio analítico de pacientes con enfermedad renal crónica G4-5 en un hospital de referencia entre enero del 2018 y diciembre del 2021, en el cual se analizaron variables sociodemográficas, clínicas y se realizó una regresión logística sobre los anticoagulantes y la frecuencia de eventos (hemorrágicos o embólicos). Resultados: se evaluó a 75 pacientes con diagnóstico de enfermedad renal crónica G4-5 anticoagulados, donde el anticoagulante más usado fue warfarina (76 %), seguido de apixabán (16 %) y rivaroxabán (8 %). El sangrado mayor se presentó con warfarina (8,47 %), apixabán (10%) y rivaroxabán (16,6 %). No se encontraron diferencias significativas entre el sangrado mayor con warfarina (OR: 2,8; IC 95 %: 0,46-16,9; p = 0,262) y rivaroxabán (OR: 1,86; IC 95 %: 0,18-18,7; p = 0,596), además, el sangrado no mayor y clínicamente relevante fue del 28,9 % con warfarina. Solo se presentó una complicación trombótica en un paciente que recibió rivaroxabán. Conclusiones: en los pacientes con enfermedad renal G4-5 que recibieron warfarina y los anticoagulantes orales directos no se encontraron diferencias significativas en cuanto a la presentación de sangrado mayor y no mayor, clínicamente relevantes.

Background: Anticoagulation in patients with chronic kidney disease is a therapeutic challenge since the medical evidence is scarce and the benefits are debatable since the risk of bleeding in these patients is greater. Purpose: To describe patients with G4-5 kidney disease who received oral anticoagulant therapy for at least 3 months in the central-eastern subnetwork of Bogotá. Methodology: Analytical study of patients with G4-5 chronic kidney disease, in a reference hospital between January 2018 and December 2021, in which sociodemographic and clinical variables were analyzed, and a logistic regression was performed on anticoagulants and the frequency of events (hemorrhagic or embolic). Results: 75 anticoagulated patients diagnosed with G4-5 chronic kidney disease were evaluated. The most commonly used anticoagulant was warfarin (76%), apixaban (16%), and rivaroxaban (8%). Major bleeding occurred with warfarin (8.47%), apixaban (10%), and rivaroxaban (16.6%). There are no significant differences between major bleeding with warfarin (OR: 2.8; 95% CI: 0.46;16.9; p= 0.262), and rivaroxaban (OR: 1.86; 95% CI: 0.18;18.7; p=0.596). Clinically relevant non-major bleeding was 28.9% with warfarin. A thrombotic complication only occurred in one patient who received rivaroxaban. Conclusions: In patients with G4-5 kidney disease who received warfarin and direct oral anticoagulants, no significant differences were found in terms of the presentation of clinically relevant major and non-major bleeding.

Describing the Oral Health of Warfarin Users. A Short Report

Aim: To describe the burden of oral diseases and of self-reported periodontal disease of patients under Oral Anticoagulation Therapy (OAT) with warfarin. Methods: A cross-sectional study was conducted. Validated questionnaires assessed self-reported periodontal disease and demographic variables. After calibration (Kappa > 0.80), an examiner evaluated dental caries and the need for dental prostheses. Statistical analysis involved proportions and measures of central tendency. Results: The sample consisted of 158 individuals, with a mean age of 58.8 years (SD = 12.1), of which 62.7% of the participants were women. The average DMFT (Decayed, Missing, and Filled Teeth) index was 22.9 (SD = 7.6), with the missing component being the highest (Mean = 16.23). The use of maxillary prosthesis (53.2%) was higher than mandibular (32.3%). The need for mandibular prosthesis reached 66.5%. The percentage of participants that referred gum disease, tooth migration, and tooth mobility was 29.6%, 37.4%, and 30.4%, respectively. Conclusions: The burden of oral diseases among individuals undergoing OAT is worrisome.

Objetivo: Describir la carga de enfermedades bucales y la enfermedad periodontal autorreportada de pacientes en tratamiento con anticoagulación oral con warfarina. Métodos: Se realizó un estudio transversal. Los cuestionarios validados evaluaron la enfermedad periodontal autoinformada y las variables demográficas. Después de la calibración (Kappa> 0.80), un examinador evaluó la caries dental y la necesidad de prótesis dentales. El análisis estadístico involucró proporciones y medidas de tendencia central. Resultados: La muestra estuvo formada por 158 individuos, con una edad media de 58.8 años (DE = 12.1), de los cuales el 62.7% de los participantes eran mujeres. El índice CPOD promedio fue de 22.9 (DE = 7.6), siendo el componente perdido el que más contribuyó al índice (Media = 16.23). El uso de prótesis maxilar (53.2%) fue mayor que el de prótesis mandibular (32.3%). La necesidad de prótesis mandibular alcanzó el 66.5%. El porcentaje de participantes que informaron enfermedad de las encías, migración de los dientes y movilidad de los dientes fue del 29.6%, 37.4% y 30.4%, respectivamente. Conclusiones: Las enfermedades bucales y la necesidad de rehabilitación oral entre los individuos sometidos a anticoagulación oral con warfarina fue motivo de preocupación.

Hematoma de la vaina de los rectos abdominales en el curso de la COVID-19

Introducción: El hematoma espontáneo de la pared abdominal constituye una entidad clínica poco frecuente en la práctica médica. En el contexto de la COVID-19 el hematoma intraabdominal se presentó como complicación de la terapéutica impuesta y no fue tomado en consideración al realizar el diagnóstico diferencial del dolor abdominal e hipotensión arterial. Objetivo: Reportar la aparición de hematoma de la vaina de los rectos abdominales como complicación del empleo de anticoagulantes en el curso del tratamiento de la COVID-19. Caso clínico: Se presenta una paciente de 71 años de edad con la COVID-19 que se encontraba con tratamiento anticoagulante y comenzó con dolor abdominal agudo, con ecografía abdominal que no fue concluyente, se realizó laparotomía y se encontró gran hematoma en el espacio de Retzius. Evolucionó favorablemente y es dada de alta a los 7 días. Conclusiones: El diagnóstico transoperatorio conjuntamente con el drenaje del hematoma y la fluidoterapia oportuna permitió una evolución favorable y la recuperación de la paciente.

Introduction: Spontaneous abdominal wall hematoma is a rare clinical entity in medical practice. In the context of COVID-19, intra-abdominal hematoma presented as a complication of the imposed therapy and was not taken into consideration when making the differential diagnosis of abdominal pain and arterial hypotension. Objective: To report the appearance of rectus abdominis sheath hematoma as a complication of the use of anticoagulants in the course of COVID-19 treatment. Clinical case: A 71-year-old patient with COVID-19 is presented who was receiving anticoagulant treatment and began with acute abdominal pain, with abdominal ultrasound that was inconclusive, laparotomy was performed and a large hematoma was found in the abdominal Retzius space. She evolved favourably and is discharged after 7 days. Conclusions: The trans-operative diagnosis together with the drainage of the hematoma and the opportune fluid therapy allowed a favourable evolution and the recovery of the patient.

Plantar vein thrombosis: an uncommon cause of plantar foot pain / Trombose venosa plantar: uma causa incomum de dor em região plantar

INTRODUCTION: Plantar vein thrombosis is a rare condition that can lead to pain, edema, and walking difficulties. It presents a series of predisposing factors, such as recent surgeries, the use of oral contraceptives, and local trauma, among others. Imaging tests are essential for the right diagnosis, and ultrasonography is the modality of choice. As for treatment, there is no consensus in the literature. REPORT: Case of a 30-year-old patient who sought emergency medical care complaining of sudden severe pain in the plantar region of her right foot with walking difficulties. On physical examination, hyperalgesia was observed in the plantar region, irradiating to the calf, associated with swelling. Color Doppler imaging identified an acute thrombus in the medial plantar vein. Rivaroxaban was initially prescribed and replaced by acetylsalicylic acid after three months. The treatment was effective, and the patient was discharged after 11 months. CONCLUSION: Plantar vein thrombosis is a rare condition and has a wide range of differential diagnoses so physicians must maintain a high level of clinical suspicion. To improve diagnosis and treatment, it would be necessary to include plantar veins in the investigation protocols of patients suspected of having Deep Venous Thrombosis, besides additional clinical research for improving treatment.

INTRODUÇÃO: A trombose de veias plantares é uma condição rara que pode cursar com dor, edema e dificuldade na deambulação. Apresenta uma série de fatores predisponentes, como cirurgias recentes, uso de anticoncepcional oral, trauma local, entre outros. A realização de exame de imagem é essencial para o diagnóstico, sendo a ultrassonografia a modalidade de escolha. Quanto ao tratamento, não há consenso na literatura. RELATO: Relatamos o caso de uma paciente de 30 anos que procurou atendimento médico de urgência com queixa de dor de forte intensidade, súbita, em região plantar do pé direito com dificuldade de deambulação. Ao exame físico, observou-se hiperalgesia em região plantar com irradiação para panturrilha, associada a empastamento da mesma. O ecodoppler colorido identificou trombo agudo em veia plantar medial. Optou-se pela prescrição de rivaroxabana, a qual foi substituída por ácido acetilsalicílico após três meses. A paciente evoluiu bem e recebeu alta do tratamento após 11 meses. CONCLUSÃO: A trombose de veias plantares é rara e tem uma alta gama de diagnósticos diferenciais, de forma que o profissional médico deve manter um alto nível de suspeição clínica. Para aperfeiçoar seu diagnóstico e tratamento, seria necessária a inclusão das veias plantares aos protocolos de investigação de pacientes com suspeita de Trombose Venosa Profunda, e pesquisas clínicas que elucidassem os melhores métodos terapêuticos.

Fibrilación auricular una arritmia y un sindrome / Atrial fibrillation, an arrhythmia and a syndrome

Atrial Fibrillation (AF) is the most common sustained arrhythmia and is highly prevalent in elderly patients. It confers a higher risk for ischemic stroke, heart failure and death. The diagnosis and treatment of AF has been extensively studied and remain under constant revision. This article reviews the recent European guidelines and the advances observed with the introduction of direct oral anticoagulants in the last ten years. This new family of drugs has clear benefits in terms of efficacy and safety compared with traditional vitamin K antagonists. Treatment of most common comorbidities in patients with AF such as advanced age, heart failure, diabetes, renal failure, and others are also analyzed. New therapies for AF will be shortly available.

Performance of the ATRIA Bleeding Score in Predicting the Risk of In-Hospital Bleeding in Patients with ST-Elevation or Non-ST-Elevation Myocardial Infarction

ABSTRACT Introduction: A clear assessment of the bleeding risk score in patients presenting with myocardial infarction (MI) is crucial because of its impact on prognosis. The Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA score is a validated risk score to predict bleeding risk in atrial fibrillation (AF), but its predictive value in predicting bleeding after percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) patients receiving antithrombotic therapy is unknown. Our aim was to investigate the predictive performance of the ATRIA bleeding score in STEMI and NSTEMI patients in comparison to the CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines) and ACUITY-HORIZONS (Acute Catheterization and Urgent Intervention Triage strategY-Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) bleeding scores. Methods: A total of 830 consecutive STEMI and NSTEMI patients who underwent PCI were evaluated retrospectively. The ATRIA, CRUSADE, and ACUITY-HORIZONS risk scores of the patients were calculated. Discrimination of the three risk models was evaluated using C-statistics. Results: Major bleeding occurred in 52 (6.3%) of 830 patients during hospitalization. Bleeding scores were significantly higher in the bleeding patients than in non-bleeding patients (all P<0.001). The discriminatory ability of the ATRIA, CRUSADE, and ACUITY-HORIZONS bleeding scores for bleeding events was similar (C-statistics 0.810, 0.832, and 0.909, respectively). The good predictive value of all three scores for predicting the risk of bleeding was observed in NSTEMI and STEMI patients as well (C-statistics: 0.820, 0.793, and 0.921 and 0.809, 0.854, and 0.905, respectively). Conclusion: This study demonstrated that the ATRIA bleeding score is a useful risk score for predicting major in-hospital bleeding in MI patients. This good predictive value was also present in STEMI and NSTEMI patient subgroups.

Factores de riesgo cardiometabólico y tratamiento antitrombótico en población mexicana con fibrilación auricular e insuficiencia cardiaca con fracción de expulsión reducida / Cardiometabolic risk factors and antithrombotic treatment in a Mexican population with atrial fibrillation and heart failure with reduced ejection fraction

Resumen Introducción: La insuficiencia cardiaca en pacientes con fibrilación auricular no valvular (FANV) es de dos a tres veces más frecuente que en individuos sin FANV. Objetivo: Identificar los factores de riesgo cardiometabólico (FRCM) y el tratamiento antitrombótico de pacientes con FANV e insuficiencia cardiaca con fracción de expulsión reducida (IC-FEr), y determinar si existen diferencias conforme al sexo. Métodos: En forma global y de acuerdo con el sexo se analizaron FRCM, riesgo protrombótico, riesgo de sangrado y terapia antitrombótica. Resultados: De 1423 pacientes con FANV, 336 tuvieron IC-FEr. Las mujeres promediaron mayor edad que los hombres. No hubo diferencia entre los sexos respecto al tipo de FANV o uso de anticoagulantes orales directos. La hipertensión arterial sistémica fue más frecuente en mujeres. Un 3.6 % de los pacientes reportó antecedente de ataque isquémico transitorio y 10 % de evento vascular cerebral, sin diferencias en cuanto al sexo. El porcentaje de hombres con riesgo embólico elevado fue mayor, pero sin tratamiento antitrombótico, en comparación con las mujeres. Conclusiones: Se encontraron diferencias significativas de acuerdo con el sexo en pacientes con FANV e IC-FEr, tanto en FRCM y algunas comorbilidades, como en el tratamiento antitrombótico de acuerdo con el riesgo embólico y de sangrado.

Abstract Introduction: Heart failure in patients with non-valvular atrial fibrillation (NVAF) is two to three times more common than in individuals without NVAF. Objective: To identify cardiometabolic risk factors (CMRF) and antithrombotic treatment in patients with NVAF and heart failure with reduced ejection fraction (HFrEF), and to determine if there were differences according to gender. Methods: CMRF, pro-thrombotic risk, bleeding risk, and antithrombotic therapy were globally analyzed and according to gender. Results: Out of 1,423 patients with NVAF, 336 had HFrEF. On average, females were older than males. There was no difference between genders with regard to the type of NVAF or direct oral anticoagulants use. Hypertension was more common in women. History of transient ischemic attack was reported in 3.6% of the patients and cerebrovascular event in 10%, without differences in terms of gender. The percentage of men with elevated embolic risk was higher, but without antithrombotic treatment, in comparison with women. Conclusions: Significant differences were found according to gender in patients with NVAF and HFrEF, both in CMRF and some comorbidities, as well as in antithrombotic treatment according to embolic and bleeding risk.

Uso inadecuado del fármaco acenocumarol en la fibrilación auricular no valvular

Introducción: El uso del acenocumarol como anticoagulante, constituye un aporte al tratamiento de la fibrilación auricular no valvular. En la actualidad existen otros tipos de anticoagulantes que no requieren control tan exhaustivo de la prueba digital International Normaizedl Ratio y tienen menos efectos secundarios. España es uno de los pocos países de Europa que continúa indicando acenocumarol, de forma similar a la warfarina. Tanto es así, que a los médicos de atención primaria no se les permite prescribir otros anticoagulantes más eficaces y menos molestos, para el paciente al realizar la prueba digital. Objetivo: Analizar el uso inadecuado del fármaco acenocumarol en la fibrilación auricular no valvular. Métodos: Se realizó un estudio exploratorio, en un sistema de salud de atención primaria y hospitales de categoría secundaria. La población la integraron 2 650 habitantes del sureste español con fibrilación auricular no valvular, tomadores de acenocumarol con seguimiento de 12 meses. Resultados: Se consideró las variaciones y labilidad del valor International Normalized Ratio, entre 2,0-3,0 en determinaciones cada 28 días, no obstante a la enfermedad cardiovascular y cifras obtenidas respecto a las anteriores. El tiempo de seguimiento fue 12 meses y desapareció la fragilidad, se tomaron muestras cada 28 días. Antes de finalizar el estudio, desapareció la labilidad del International Normalized Ratio durante más de tres meses en 53 (97,95 %) de los pacientes. Dado que la mayoría de los enfermos que consumían acenocumarol tenían edades por encima de 65 años y estaban sometidos a régimen de poli medicación, los medicamentos que consumían, fueron motivo de evaluación. Conclusiones: El tiempo transcurrido entre la determinación del International Normaizedl Ratio y la última ingesta de alimentos y medicamentos, no fue correcto, existe tendencia a realizar determinaciones anárquicas del International Normalized Ratio, sin investigaciones relacionadas con fármacos consumidos junto al acenocumarol.

Introduction: The use of acenocoumarol as an anticoagulant represents a contribution to the treatment of non-valvular atrial fibrillation. At present, there are other types of anticoagulants that do not require such exhaustive control of the International Normalized Ratio digital test and have fewer side effects. Spain is one of the few countries in Europe that continues to prescribe acenocoumarol, which is similar to warfarin. So much so that primary care physicians are not allowed to prescribe other more effective and less troublesome anticoagulants for the patient when performing the digital test. Objective: To analyze the inappropriate use of the drug acenocoumarol in non-valvular atrial fibrillation. Methods: An exploratory study was carried out in a primary health care system and secondary category hospitals. The population consisted of 2650 inhabitants of southeastern Spain with non-valvular atrial fibrillation, taking acenocoumarol with 12 months follow-up. Results: We considered the variations and lability of the International Normalized Ratio value, between 2.0-3.0 in determinations every 28 days, regardless of cardiovascular disease and figures obtained in relation to the previous. The follow-up time was 12 months and the lability disappeared, samples were taken every 28 days. Before the end of the study, the lability of the International Normalized Ratio disappeared for more than three months in 53 (97.95%) of the patients. Since most of the patients taking acenocoumarol were over 65 years of age and on polymedication, the medications taken by each of them were evaluated. Conclusions: The time elapsed between the International Normalized Ratio determination and the last intake of food and medication was not correct, and there is a tendency to perform anarchic determinations of the International Normalized Ratio without investigations related to drugs consumed together with acenocoumarol.

Agentes antitrombóticos utilizados por pessoas idosas: prevalência e fatores associados / Antithrombotic agents used by older people: prevalence and associated factors

Resumo Objetivo Analisar os tipos e a prevalência da utilização de medicamentos antitrombóticos por pessoas idosas, e os fatores associados. Método Estudo transversal com pessoas idosas domiciliares, na cidade de Goiânia, Centro-Oeste do Brasil. A classificação farmacológica dos medicamentos antitrombóticos foi efetuada de acordo com a classificação Anatômico Terapêutico Químico (Anatomical Therapeutic Chemical - ATC). Realizada análise bivariada e múltipla com nível de significância de 5%. Resultados Participaram do estudo 212 idosos com prevalência de uso de medicamentos antitrombóticos de 27,8%. Os tipos mais utilizados foram: ácido acetilsalicílico (AAS) (n= 49; 83%), Clopidogrel (n=6; 10,1%) e Cilostazol (n=4; 6,7%). Os fatores associados foram: faixa etária de 70-79 anos (p<0,001) e a polifarmácia (p<0,001). Conclusão A proporção do uso de antitrombóticos foi alta entre os idosos, e os fármacos mais consumidos possuem risco de complicações e de interações medicamentosas. A vigilância deve ser maior naqueles com mais de 70 anos e em polifarmácia, sendo necessário empreender esforços para o acompanhamento clínico desses idosos em terapia antitrombótica farmacológica.

Abstract Objective To analyze the types and prevalence of use of antithrombotic drugs by older people and associated factors. Method A cross-sectional study of community-dwelling older people was carried out in the city of Goiânia, Midwest Brazil. The pharmacological classification of antithrombotic drugs was performed according to the Anatomical Therapeutic Chemical (ATC) classification. Bivariate and multivariate analyses were performed with a significance level of 5%. Results 212 older people participated in the study and the prevalence of antithrombotic drug use was 27.8%. The most used types were acetylsalicylic acid (ASA) (n= 49; 83%), Clopidogrel (n=6; 10.1%) and Cilostazol (n=4; 6.7%). Associated factors were the 70-79 years age group (p<0.001) and polypharmacy (p<0.001). Conclusion The proportion of antithrombotic use by the participants was high and the most used drugs posed a risk of complications and drug-drug interactions. Attention should be heightened in individuals aged >70 years and in use of polypharmacy and efforts must be made to clinically monitor these users of antithrombotic drugs therapy.

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.

Telemonitoramento de idosos usuários de anticoagulante durante a pandemia da COVID-19 / Telemonitoring of older anticoagulant users during the COVID-19 pandemic

A pandemia da COVID-19 trouxe desafios para o monitoramento de usuários de anticoagulantes, sobretudo idosos, sendo o telemonitoramento uma alternativa para dar continuidade aos cuidados para esses pacientes. O presente estudo teve como objetivo descrever a experiência do telemonitoramento de idosos usuários de anticoagulantes na pandemia da COVID-19. Trata-se de estudo referente ao serviço farmacêutico de telemonitoramento de idosos (≥60 anos) em uso de anticoagulantes orais em ambulatório de geriatria privado (Belo Horizonte). Idosos tiveram parâmetros de efetividade e segurança dos anticoagulantes monitorados mensalmente por telefone (abr-dez/2021). Problemas identificados geraram intervenções ao paciente ou equipe multiprofissional. Ao total 425 idosos foram incluídos no serviço. A maioria usava apixabana (189;41,9%), rivaroxabana (146;34,4%) e varfarina (47;11,1%). Observou-se média de idade de 82,1 anos, maioria feminina (65,2%), maioria com alto risco de vulnerabilidade (69%), e incidência de 9,9% de COVID-19. Realizou-se 219 intervenções relativas à varfarina (média de 4,6 intervenções/paciente); referiram-se à solicitação de exame de RNI (57,5%), orientações em saúde (19,6%), alteração da dose (redução - 10,5%; aumento - 5,9%; suspensão - 0,6%), ou encaminhamento (5,9%). Usuários de outros anticoagulantes não apresentaram alterações nos parâmetros acompanhados. Onze idosos sofreram quedas e 10 demandaram internação por eventos tromboembólicos ou hemorrágicos. Não houve diferença estatisticamente significativa nas proporções de internação entre usuários de varfarina ou outros anticoagulantes (p=0,314). Acompanhar idosos usuários de anticoagulantes é importante, sobretudo considerando-se o alto nível de fragilidade identificado e os riscos tromboembólicos e não-tromboembólicos que a COVID-19 traz. O telemonitoramento foi importante, permitindo realização de múltiplas intervenções.

The COVID-19 pandemic brought challenges to the monitoring of anticoagulant users, especially older adults, making telemonitoring an alternative to provide continuity of care for these patients. The present study aimed to describe the experience of telemonitoring of older anticoagulant users during the COVID-19 pandemic. This is a descriptive study concerning the telemonitoring pharmaceutical service for older adults (≥60 years old) using oral anticoagulants in a private geriatric outpatient clinic (Belo Horizonte). Older people had parameters of effectiveness and safety of anticoagulants monitored monthly by telephone (Apr-Dec/2021). Identified problems generated interventions for the patient or the multidisciplinary team. A total of 425 older adults were included in the service. Most used apixaban (189;41.9%), rivaroxaban (146;34.4%) and warfarin (47;11.1%). There was a mean age of 82.1 years, mostly female (65.2%), most at high risk of vulnerability (69%), and an incidence of 9.9% of COVID-19. There were 219 interventions related to warfarin (average of 4.6 interventions/patient); including requests for an INR test (57.5%), health guidelines (19.6%), dosage change (reduction - 10.5%; increase - 5.9%; suspension - 0.6%), or referral (5.9%). Users of other anticoagulants did not show alterations in the monitored parameters. Eleven older adults suffered falls and 10 required hospitalizations due to thromboembolic or hemorrhagic events. There was no statistically significant difference in hospitalization rates between users of warfarin or other anticoagulants (p=0.314). Monitoring older anticoagulant users is important, especially considering the high level of frailty identified and the thromboembolic and non-thromboembolic risks that COVID-19 brings. Telemonitoring was important, allowing for multiple interventions to be performed.

Análise da qualidade das evidências científicas sobre a eficácia e segurança nas bulas de anticoagulantes orais diretos comercializados no Brasil / Analysis of the quality of scientific evidence on efficacy and safety in the package leaflets of direct oral anticoagulants marketed in Brazil

Objetivo: Identificar e analisar a qualidade das evidências científicas sobre a eficácia e segurança dos anticoagulantes orais direto (DOAC) disponíveis nos ensaios clínicos referenciados nas bulas dos medicamentos comercializados no Brasil. Método: Trata-se de um descritivo documental dividido em duas etapas, sendo elas: (i) identificação e análise da disponibilidade das referências bibliográficas contidas nas bulas dos DOAC e (ii) análise da qualidade dos estudos contidos nas bulas através da ferramenta da Cochrane Risk of Bias RevMan versão 5.4. Foram analisados setes domínios de importâncias para ensino clínico, sendo que cada domínio foi classificado como alto, incerto ou baixo risco de viés, segundo a avaliação dos colaboradores. Resultados: Foram analisadas 10 bulas destinadas aos profissionais da saúde. Sendo que destas, foram avaliados 25 ensaios clínicos. A análise da qualidade das evidências científicas, referenciadas nas bulas para profissionais dos DOAC, mostrou que os estudos citados apresentaram consistência metodológica. Entretanto, na maioria dos estudos, os domínios foram classificados como viés incerto, ou seja, não foi possível identificar como esses pontos foram abordados nos estudos. Conclusão: Portanto, o presente estudo evidenciou que a qualidade dos ensaios clínicos referenciados nas bulas dos DOAC apresentou incertezas metodológicas em seus ensaios. Sugere-se a necessidade de normativas que estabeleçam atualizações do conteúdo informativo presente nas bulas profissionais e estabeleçam descrição dos métodos de forma clara e coesa (AU).

Objective: Identify and analyze the quality of scientific evidence on the efficacy and safety of direct oral anticoagulants (DOAC) available in clinical trials referenced in the package leaflets of drugs marketed in Brazil. Method: This is a descriptive documentary study divided into two stages: (i) identification and analysis of the availability of the bibliographic references contained in the package leaflets of DOACs and (ii) analysis of the quality of the studies contained in the package leaflets through the Cochrane Risk of Bias RevMan tool version 5.4. Seven domains of importance for clinical teaching were analyzed, and each domain was classified as high, uncertain or low risk of bias, according to the assessment of the collaborators. Results: Ten package leaflets intended for health professionals were analyzed. Of these, 25 clinical trials were evaluated. The analysis of the quality of the scientific evidence referenced in the package leaflets for health professionals showed that the cited studies presented methodological consistency. However, in most studies, the domains were classified as uncertain bias, i.e., it was not possible to identify how these points were addressed in the studies. Conclusion: Therefore, the present study evidenced that the quality of clinical trials referenced in the package leaflets of DOACs presented methodological uncertainties in their trials. It is suggested the need for regulations that establish updates of the information content present in the professional package inserts and establish a description of the methods in a clear and cohesive way (AU).