Association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia in patients receiving dabigatran after total knee arthroplasty / 中华创伤杂志(英文版)

PURPOSE@#Dabigatran is usually prescribed in recommended doses without monitoring of the blood coagulation for the prevention of venous thromboembolism after joint arthroplasty. ABCB1 is a key gene in the metabolism of dabigatran etexilate. Its allele variants are likely to play a pivotal role in the occurrence of hemorrhagic complications.@*METHODS@#The prospective study included 127 patients with primary knee osteoarthritis undergoing total knee arthroplasty. Patients with anemia and coagulation disorders, elevated transaminase and creatinine levels as well as already receiving anticoagulant and antiplatelet therapy were excluded from the study. The association of ABCB1 gene polymorphisms rs1128503, rs2032582, rs4148738 with anemia as the outcome of dabigatran therapy was evaluated by single-nucleotide polymorphism analysis with a real-time polymerase chain reaction assay and laboratory blood tests. The beta regression model was used to predict the effect of polymorphisms on the studied laboratory markers. The probability of the type 1 error (p) was less than 0.05 was considered statistically significant. BenjaminiHochberg was used to correct for significance levels in multiple hypothesis tests. All calculations were performed using Rprogramming language v3.6.3.@*RESULTS@#For all polymorphisms there was no association with the level of platelets, protein, creatinine, alanine transaminase, prothrombin, international normalized ratio, activated partial thromboplastin time and fibrinogen. Carriers of rs1128503 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.015) while receiving dabigatran therapy during the postoperative period compared to the CC, CT. Carriers of rs2032582 (TT) had a significant decrease of hematocrit (p = 0.001), red blood count and hemoglobin (p = 0.006) while receiving dabigatran therapy during the postoperative period compared to the GG, GT phenotypes. These differences were not observed in carriers of rs4148738.@*CONCLUSION@#It might be necessary to reconsider thromboprophylaxis with dabigatran in carriers of rs1128503 (TT) or rs2032582 (TT) polymorphisms in favor of other new oral anticoagulants. The long-term implication of these findings would be the reduction of bleeding complications after total joint arthroplasty.

Fact-Finding Survey of Information Provision and Medication Instruction on Idarucizumab for Pharmacists / 医薬品情報学

Objective: Providing patients with information and medication instruction regarding direct oral anticoagulant (DOAC)antagonists is becoming increasingly important. Comprehensive knowledge of DOAC antagonists can expedite the transportation and treatment of emergency cases, such as bleeding with antagonists, in hospitals. We investigated the awareness of idarucizumab and whether the information provided in the Risk Management Plan was reflected in the actual provision of information and medication instruction.Methods: Pharmacists in dispensing pharmacies and Kameda Medical Center were included in the survey conducted from May 2022 to June 2022. Using a web-based questionnaire, we obtained answers to questions related to idarucizumab awareness. Respondents answered a series of questions regarding idarucizumab awareness, sources of information, patient information, and medication instruction.Results: We received responses from 1,118 people. In all, 25.9% pharmacists were aware of idarucizumab, and 10.3% provided information and medication instruction on DOAC antagonists to patients. Pharmaceutical companies, books, drug information departments, workshops, and wholesalers were the sources of information on idarucizumab for 24.8, 21.0, 19.0, 10.7, and 3.1% of the pharmacists, respectively.Conclusion: Pharmacists had knowledge of DOAC antagonists and provided information and instructions to patients infrequently. Improved awareness will lead to prompt response during the occurrence of adverse events such as bleeding.

Study on population pharmacokinetics of dabigatran in elderly patients with non-valvular atrial fibrillation / 中国药房

OBJECTIVE To analyze influential factors for dabigatran exposure in elderly patients with non-valvular atrial fibrillation. METHODS The clinical information of 75 elderly patients diagnosed with non-valvular atrial fibrillation was collected from our hospital in Jan. 2019-Jun. 2020. One or two steady-state blood drug concentration samples were collected from each patient. NONMEM 7.2.0 software was used to establish a population pharmacokinetics model of dabigatran； the effects of different covariates on the apparent clearance of dabigatran were investigated， and the final model was verified by goodness of fit and Bootstrap method； NONMEM 7.2.0 software was used to analyze the drug exposure of ordinary elderly patients and elderly patients after taking dabigatran ester in different disease states. RESULTS Totally 122 blood concentration samples of dabigatran were collected. Advanced age， creatinine clearance and history of chronic heart failure were screened out as three significant covariates that influenced the clearance of dabigatran in elderly patients. The exposure of population with advanced age increased by about 50% compared with the general elderly， the exposure of population with history of chronic heart failure increased by nearly 30% compared with population without， and the exposure of population with moderate and severe renal injury increased by about 30% and 80% compared with mild. CONCLUSIONS Advanced age， renal injury and history of chronic heart failure are influential factors for elevated systemic exposure of dabigatran.

Efficacy and safety evaluation of dabigatran etexilate in the treatment of elderly non-valvular atrial fibrillation / 药学实践杂志

Objective To explore the efficacy and safety of dabigatran etexilate in the treatment of elderly patients with non-valvular atrial fibrillation (NVAF), so as to provide reference for clinical treatment and rational drug use. Methods Eighty elderly patients with NVAF in The Seventh People's Hospital of Shanghai from December 2020 to June 2021, aged 65 to 80 years, were enrolled in a self-controlled study. Dabigatran etexilate 110 mg was given orally, twice a day (one in the morning and one in the evening) for 6 months. During the follow-up visit, the coagulation function indexes including APTT, TT, FIB and D-D were observed in patients taking medicine for 1 month and 6 months. Liver function indexes including ALT, AST and TBIL, renal function indicators including UREA and eGFR, and blood routine indexes including HGB and ESR, also were observed in patients taking medicine for 1 month and 6 months. Results Patients were compared at 1 month and 6 months after treatment with dabigatran and before: the difference of coagulation function indexes as APTT and TT was statistically significant (P<0.05);There was no significant difference in liver function index, renal function index and blood routine index (P>0.05); A total of 25 adverse events occurred, and the incidence rate of adverse reactions was 31.25%, there was no adverse events such as serious hemorrhage，life threatening and organ failure hemorrhage occurred．Conclusion Dabigatran has good efficacy and safety in the treatment of the elderly NVAF.

Recomendaciones de manejo de los anticoagulantes orales directos (DOACs) anti Xa y anti IIa / Recommendations for the practical management of the direct oral anticoagulants anti Xa and anti IIa

Resumen Los anticoagulantes orales directos han surgido como una de las herramientas que ha cambiado el manejo de la enfermedad trombótica en los últimos 15 años. Sus ventajas, desde el punto de vista de la facilidad de uso y menor riesgo de sangrado, especialmente de sangrado cerebral, han posicionado a estos nuevos anticoagulantes como la primera alternativa de tratamiento en las dos indicaciones más frecuentes en que necesitamos estas drogas, la fibrilación auricular y la enfermedad tromboembólica venosa. Sin embargo, no todos los pacientes pueden recibir estos agentes, no todos los anticoagulantes directos tienen las mismas pro piedades y fundamentalmente, no todas las enfermedades con indicación de un anticoagulante pueden tratarse con ellos;con lo cual es necesario que todos los profesionales que están involucrados en el manejo de estos medicamentos estén obligados a conocerlos en profundidad, para poder decidir el mejor tratamiento en cada caso particular. Este documento de posición de expertos de diferentes especialidades de Argentina, presenta lineamientos para el uso correcto de los anticoagulantes directos en base a nueva evidencia y a la experiencia de uso de un amplio grupo de profesionales. La forma de relacionarnos con el tratamiento anticoagulante ha cambiado. Los médicos que trabajamos con ellos también debemos hacerlo.

Abstract Direct oral anticoagulants have emerged as the drugs that have changed the man agement of the antithrombotic treatment in the last 15 years. Their advantages, like a more friendly way of anticoagulation and their lower risk of bleeding, especially in the brain, have positioned these new anticoagu lants as the first drug of choice in the two most frequent indications of anticoagulation, atrial fibrillation, and the venous thromboembolic disease. However, not all the patients can receive these agents, not all the direct oral anticoagulants have the same characteristics, and most importantly, not all the diseases with an indication of an anticoagulant drug can be treated with them. Therefore, it is mandatory that all the faculties involved in the management of these drugs must know them in depth, to decide the best treatment for the patient. This position paper, from a group of experts in anticoagulation in Argentina, can help the general practitioner in the daily use of direct oral anticoagulants based on the new evidence and the experience of a wide group of professionals. The way we relate to the anticoagulant treatment has changed in the last years. The doctors who work with them must also do so.

Anticoagulantes Orales de Acción Directa y sus Implicancias en la Exodoncia: Una Revisión Sistemática

RESUMEN: El uso de Anticoagulantes Orales de Acción Directa (ACOD) ha aumentado considerablemente en el último tiempo. En procedimientos odontológicos, como la exodoncia, es crucial un manejo óptimo de la hemostasia de pacientes bajo tratamiento con ACOD, para equilibrar el riesgo de hemorragia y tromboembolismo. Aun no existe consenso sobre el protocolo a aplicar en pacientes con ACOD sometidos a exodoncias. El objetivo fue evaluar la necesidad de suspender o continuar el tratamiento con ACOD en pacientes sometidos a exodoncia en relación con la incidencia de episodios hemorrágicos y protocolos utilizados. Se realizó una revisión sistemática en base a los estamentos PRISMA, en las bases de datos Pubmed, Wiley, Scopus. La búsqueda incluyó estudios publicados entre 2010 - 2020 en inglés, realizados en humanos, en pacientes bajo terapia con ACOD sometidos a exodoncia y que evalúan la incidencia de hemorragia en este procedimiento. Se excluyeron estudios que involucran pacientes que reciben otros tratamientos antitrombótico concomitante, o procedimientos distintos a la exodoncia. La calidad de los estudios seleccionados fue evaluada de acuerdo con la clasificación del Centro Oxford de Medicina Basada en la Evidencia. Luego de la búsqueda, en base a criterios de inclusión/exclusión, 34 artículos fueron analizados a texto completo. Trece artículos relevantes fueron seleccionados. Once participaron en la revisión final, contando con ocho estudios de cohorte, dos casos-controles y uno serie de casos. Los estudios evidencian que no es necesario suspender la terapia con ACOD en pacientes sometidos a exodoncia, se sugiere que el momento de baja concentración farmacológica puede ser utilizado a favor del tratante. Sin embargo, existe una gran diversidad de protocolos y medidas aplicadas entre estudios, por lo que es necesario realizar estudios clínicos aleatorizados controlados, para determinar un protocolo estándar en el manejo odontológico de estos pacientes.

ABSTRACT: The use of Direct Acting Oral Anticoagulants (ACOD) has increased considerably in recent times. In dental procedures, such as tooth extraction, optimal management of hemostasis in patients treated with ACOD is crucial to balance the risk of bleeding and thromboembolism. There is still no consensus on the protocol to be applied in patients with ACOD in dental extraction. The aim was to evaluate the need to suspend or continue treatment with ACOD in patients submitted to dental extraction in relation to the incidence of bleeding episodes and the protocols used. A systematic review was carried out based on the PRISMA estates, in the Pubmed, Wiley, Scopus databases. The search included studies published between 2010-2020 in English conducted in humans, in patients under therapy with ACOD submitted to dental extraction and that evaluate the incidence of bleeding in this procedure. Studies involving patients receiving other concomitant antithrombotic treatments or procedures other than dental extraction were excluded. The quality of the selected studies was evaluated according to the Oxford Center for Evidence-based Medicine classification. After the search, based on inclusion/ exclusion criteria, 34 articles were analyzed in full text. 13 relevant articles were selected. 11 participated in the final review, including 8 cohort studies, 2 case-controls and 1 case series. Studies show that it is not necessary to suspend therapy with ACOD in patients who have undergone dental extraction, it is suggested that the moment of low pharmacological concentration can be used in favor of the treatment. However, there is a great diversity of protocols and measures applied between studies, so it is necessary to carry out randomized controlled clinical studies to determine a standard protocol in the dental management of these patients.

Efecto de las diferentes drogas anticoagulantes sobre el ensayo de fibrinógeno derivado del tiempo de protrombina / Effect of different anticoagulant drugs on the prothrombin time-derived fibrinogen assay

Resumen El objetivo de este trabajo fue comparar los niveles de fibrinógeno (FBG) obtenidos por el método de Clauss con los obtenidos por el método de fibrinógeno derivado del tiempo de protrombina (FBG PT-d), con dos tromboplastinas, en pacientes anticoagulados con distintas drogas. Se estudiaron pacientes anticoagulados consecutivos: 105 con antagonistas de la vitamina K (AVK), 55 con heparina no fraccionada (HNF), 58 con heparina de bajo peso molecular (HBPM), 60 con rivaroxabán, 45 con apixabán, 60 con dabigatrán y 100 controles normales (CN). El FBG se determinó por el método de Clauss y FBG PT-d utilizando tromboplastina de cerebro de conejo o recombinante humana; los niveles de heparina, rivaroxabán y apixabán por método cromogénico anti Xa; el dabigatrán con el ensayo de tiempo de trombina diluido. Existió un sesgo positivo (p<0,001) al comparar el FBG PT-d vs. FBG por Clauss: CN: 13,7%, AVK: 31,8%, rivaroxabán: 34,8% y apixabán: 20,0% cuando se utilizó tromboplastina de conejo. En el caso de las muestras que contenían HBPM se observó este desvío con ambas tromboplastinas. El sesgo porcentual en presencia de dabigatrán y heparina no fraccionada no fue estadísticamente distinto del obtenido en el grupo control. El ensayo de FBG PT-d no debe utilizarse en pacientes anticoagulados con rivaroxabán, apixabán, HBPM o AVK, ya que sobreestima los niveles de FBG. El porcentaje de sesgo depende del tipo de tromboplastina utilizado y fue mayor con la de cerebro de conejo en el sistema de detección utilizado.

Abstract The aim of this study was to compare fibrinogen (FBG) results obtained by Clauss method (FBG-C) and by the prothrombin time-derived fibrinogen assay (FBG PT-d) with two thromboplastins in patients under anticoagulation. Consecutive anticoagulated patients were studied: 105 vitamin-K antagonist (VKA), 55 unfractioned heparin, 58 LMWH, 60 rivaroxaban, 45 apixaban and 60 dabigatran, and 100 healthy controls (NC). FBG-C was performed by Clauss and FIB PT-d with rabbit brain and human recombinant thromboplastins, respectively. Heparins, rivaroxaban and apixaban levels were measured by antiXa; dabigatran by thrombin diluted assay. A positive bias of FBG PT-d vs. FBG-C with both thromboplastins were seen in NC (13.7 and 19.0 % for HS and RP, respectively), but bias with HS in rivaroxaban, apixaban and VKA patients were significantly higher compared to NC: 34.8%, 20.0 % and 31.8 %, respectively. LMWH presented higher BIAS compared to NC with both thromboplastins. Samples with unfraction heparin and dabigatran presented similar bias to NC. FBG PT-d should not be used in patients under anticoagulant treatment because of an important overestimation of FBG could be obtained in these patients. The percentage of bias depends on the type of thromboplastin used; it was higher with rabbit brain thromboplastin in the detection system used.

Resumo O objetivo deste trabalho foi comparar os níveis de fibrinogênio (FBG) obtidos pelo método de Clauss com aqueles obtidos pelo método do fibrinogênio derivado do tempo de protrombina (FBG PT-d), com duas tromboplastinas, em pacientes anticoagulados com diferentes drogas. Pacientes anticoagulados consecutivos foram estudados: 105 com antagonista da vitamina K (AVK); 55 com heparina não fracionada (UFH); 58 com heparina de baixo peso molecular (HBPM), 60 com rivaroxabana, 45 com apixabana, 60 com dabigatrana e 100 controles normais (CN). FBG foi determinado pelo método de Clauss e FBG PT-d usando tromboplastina de cérebro de coelho ou tromboplastina humana recombinante; níveis de heparina, rivaroxabana e apixabana pelo método cromogênico anti-Xa; dabigatrana com ensaio de tempo de trombina diluída. Há um viés positivo (p<0,001) ao comparar o FBG PT-d vs FBG de Clauss: CN: 13,7%; AVK: 31,8%, rivaroxabana: 34,8% e apixabana 20,0% quando foi utilizada tromboplastina de coelho. No caso das amostras contendo HBPM, esse desvio foi observado com ambas as tromboplastinas. O viés percentual na presença de dabigatrana e heparina não fracionada não foi estatisticamente diferente daquela obtida no grupo controle. O ensaio de FBG PT-d não deve ser usado em pacientes anticoagulados com rivaroxabana, apixabana, LMWH ou VKA, pois superestima os níveis de FBG. A porcentagem de viés depende do tipo de tromboplastina utilizado e foi maior com a de cérebro de coelho, no sistema de detecção utilizado.

Safety of oral anticoagulants in advanced chronic kidney disease / Seguridad de los anticoagulantes orales en enfermedad renal crónica avanzada

Abstract Background: patients who take long-term oral anticoagulants and also have CKD have a greater probability of bleeding. Methods: a retrospective, descriptive cohort study reviewing the clinical charts of anticoagulated patients with Stage 3 CKD or above seen at an anticoagulation clinic, in order to evaluate hemorrhagic events and baseline characteristics of the population over a two-year period. Results: 238 patients were included. The anticoagulants used were warfarin (45%), rivaroxaban (31.5%), apixaban (14.3%) and dabigatran (3.4%). According to the KDIGO classification, 78% of the patients had CKD G3 (37.3% G3a and 40.7% G3b), 15.9% G4 and 5.8% G5 with renal replace ment therapy (RRT). During the study period, only 20 patients (8.4%) had hemorrhagic events; of these, seven (35%) were major (four associated with warfarin, two with rivaroxaban and one with apixaban). The other 13 bleeds were minor and associated with warfarin in 46.1% of the cases. Gastrointestinal bleeding was the most common (35%), followed by soft tissues (30%). There was only one fatal bleed, which occurred in the central nervous system (CNS) in a patient with CKD G4. Conclusion: a low rate of bleeding was found, which could be related to close follow up by an anticoagulation clinic. The anticoagulant most frequently associated with bleeding was warfarin, which could be related to a low time in therapeutic range (48.8%). Due to the low rate of events, comparisons could not be made. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1945).

Resumen Antecedentes: los pacientes que toman anticoagulantes orales a largo plazo y además cursan con enfermedad renal crónica (ERC), tienen mayor probabilidad de tener sangrados. Métodos: estudio de cohorte descriptivo retrospectivo en el cual se revisaron historias clínicas de pacientes anticoagulados y con ERC 3 en adelante, atendidos en una clínica de anticoagulación con el fin de evaluar eventos hemorrágicos y características básales de la población en un periodo de dos años Resultados: se incluyeron 238 pacientes. Los anticoagulantes usados fueron warfarina (45%), rivaroxabán (31.5%), apixabán (14.3%) y dabigatrán (3.4%). Según la clasificación KDIGO 78% de los pacientes tenían ERC G3 (37.3% G3a y 40.7% G3b), 15.9% G4 y 5.8% G5 con terapia de reemplazo renal (TRR). En el periodo de estudio solo 20 pacientes (8.4%) tuvieron eventos hemo rrágicos, de estos, 7 (35%) fueron mayores (cuatro asociados a warfarina, dos rivaroxabán y uno apixabán). Los otros 13 sangrados fueron menores y asociados a warfarina en 46.1% de los casos. El sangrado digestivo fue el más frecuente (35%), seguido por tejidos blandos (30%). Sólo hubo un sangrado fatal el cual se dio en sistema nervioso central (SNC) en un paciente con ERC G4. Conclusión: se apreció una baja tasa de sangrado, lo que podría estar relacionado con el estrecho seguimiento de una clínica de anticoagulación. El anticoagulante que más frecuentemente se asoció con sangrado fue warfarina, lo cual puede estar relacionado con un bajo tiempo en rango terapéutico (48.8%). Por la baja tasa de eventos, no fue posible la realización de comparaciones. (Acta Med Colomb 2021; 46. DOI: https://doi.org/10.36104/amc.2021.1945).

Experiencia con idarucizumab como agente reversor de dabigatran / Experience with idarucizumab as a reverse agent of dabigatran

Resumen Los anticoagulantes orales directos (AOD), entre ellos dabigatrán, poseen un perfil riesgo-beneficio favorable comparados con warfarina y además no requieren monitoreo del efecto anticoagulante. Sin embargo, en ocasiones de sangrado con amenaza de vida o requerimiento de procedimiento quirúrgico de emergencia, es de gran utilidad revertir inmediatamente el efecto anticoagulante. Idarucizumab, fragmento de un anticuerpo monoclonal humanizado, revierte inmediatamente el efecto de dabigatrán y es actualmente el único agente reversor de un AOD disponible en Argentina. Presentamos una serie de 8 pacientes a los que se les administró idarucizumab para revertir el efecto de dabigatrán. Todos eran mayores de 65 años, recibían 110 o 150 mg cada 12 horas de dabigatrán y 7/8 estaban anticoagulados por fibrilación auricular; tres tenían indicación discutida para AOD y otro, una dosis mayor a la recomendada. Dos requirieron reversión debido a una cirugía de urgencia, y 6 tuvieron sangrado con amenaza de vida: tres hemorragias digestivas y tres sangrados intra-craneanos (en dos ocasiones traumático). En todos los casos se observó normalización de la hemostasia quirúrgica o control de sangrado crítico. No se observaron complicaciones trombóticas posteriores a la administración del antídoto. Dos fallecieron dentro de los 30 días de la administración por causas no relacionadas con la reversión. Ninguno de nuestros pacientes requirió administración de una segunda dosis de idarucizumab. Nuestro resultado es similar a lo informado en la literatura internacional.

Abstract Direct oral anticoagulants (DOACs), among them dabigatran, have a favorable benefit-risk profile compared with warfarin, and no monitoring of the anticoagulant effect is required. However, reversing the anticoagulant effect immediately is very useful in cases of life-threatening bleeding and emergency surgical procedure requirement. Idarucizumab, a humanized monoclonal antibody fragment, is currently the only reversal agent of a DOAC available in Argentina. Idarucizumab immediately reverse the effect of dabigatran. We present a series of 8 real-life clinical cases who received idarucizumab to reverse the effect of dabigatran. All of the patients were older than 65 years, were receiving 110 or 150 mg every 12 hours of dabigatran and 7/8 were anticoagulated because of atrial fibrillation. Three had a debatable indication for DOACs and another, a higher dose than recommended. Two required reversal due to emergency surgery, and 6 cases had life-threatening bleeding: three gastrointestinal hemorrhages and three intracranial bleeding (Two had a head trauma). In all cases normalization of surgical hemostasis or control of critical bleeding was observed. No hemorrhagic or thrombotic complications were observed after antidote administration. Two died within 30 days of administration of idarucizumab, due to causes unrelated to the reversal. None of our patients required administration of a second dose of idarucizumab. Our result is similar to that reported in international literature.

Predictive value of four score systems on the bleeding risk in atrial fibrillation patients treated with dabigatran / 中华心血管病杂志

Objective: To compare the predictive value of HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores on the bleeding risk in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran. Methods: Data of 942 NVAF patients participating a non-interventional prospective study of anticoagulant therapy with dabigatran, which was conducted in 12 centers from February 2015 to December 2017 in China, were analyzed. Complete HAS-BLED HEMORR2HAGES, ATRIA and ORBIT bleeding risk scores data and follow-up data were available in the enrolled patients. The endpoint of the study was bleeding events occurred during a 6 months follow-up. Cox proportional hazards models were constructed to analyze the associations between HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores and risk of bleeding, and the area under the curve (AUC) of receiver operating characteristics curves (ROC) of each score was used to set the predictive value for bleeding risk. Results: Among the 942 patients, the mean age was (65.3±11.2) years old, 542 (57.5%) were males. A total of 93 (9.9%) bleeding events occurred during follow up, 89 (9.4%) events were minor bleeding, and 4 (0.4%) events were major bleeding. Patients with a high-risk HAS-BLED score had a 1.87-fold increased risk of bleeding compared with low-risk patients (HR = 2.87, 95% CI:1.26-6.51, P = 0.012). There was no statistically significant difference between low-medium-high-risk grading in other scoring systems and bleeding risk (all P>0.05). The AUC (95%CI) of HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT bleeding risk scores were 0.558 (0.525-0.590), 0.520 (0.487-0.553), 0.513(0.480-0.545), 0.523(0.490-0.555), respectively. The AUC of all bleeding score systems were of ≤ 0.700. Conclusion: Among the NVAF patients taking dabigatran in China, the HAS-BLED bleeding risk score is superior to other 3 bleeding risk score on predicting the bleeding risk in these patients, but its predictive value is still relatively low.

Safety and Efficacy of Dabigatran Versus Warfarin in Asian Patients With Atrial Fibrillation

@#Introduction: Nonvalvular atrial fibrillation is a common cause of cardioembolic stroke which accounts around 50% of all cardioembolic emboli. Oral anticoagulants remain the main choice of stroke prevention in patients with atrial fibrillation. Our study is aimed to determine the safety (absence or presence of bleeding events) and efficacy (absence or presence of ischemic stroke occurrence) of dabigatran versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation. Methods: A retrospective audit study was conducted based on past data obtained from Electronic Hospital Information System (EHIS) records in Serdang Hospital. Our sample was 150 patients with nonvalvular atrial fibrillation who were at risk of getting stroke and being prescribed with oral anticoagulants either warfarin or dabigatran from the year 2013 until 2019. Results: Our study showed that there was lesser occurrence of ischemic stroke in patients from dabigatran group (1.3%) as compared to those in warfarin group (2.7%). There were also almost 2 times lesser bleeding events in dabigatran group (6.7%) as compared to those in warfarin group (14.7%). The median of CHA2DS2-VASc Score in warfarin sampled patients (median=3+/-1) was lower than dabigatran sampled patients (median=4+/-1). Conclusion: Both warfarin and dabigatran are effective in preventing stroke for patients with nonvalvular atrial fibrillation. However, dabigatran is associated with lesser bleeding events with lower incidence of major bleeds compared to warfarin.

A Case of Giant Mobile Left Atrial Thrombus during Dabigatran Therapy / 日本心臓血管外科学会雑誌

Dabigatran is a new/direct oral anticoagulant drug unlike warfarin. It is being increasingly used to prevent thromboembolism in patients with nonvalvular atrial fibrillation. We present the case of a 77-year-old woman with a giant left atrial thrombus in spite of anticoagulation therapy with dabigatran 300 mg/day. She had developed a cerebral infarction 18 months previously and was switched from warfarin to dabigatran. However, magnetic resonance imaging showed multiple new cerebral infarcts, and computed tomography scan and echocardiogram revealed a giant thrombus measuring 37×29 mm in the left atrium. Thrombectomy and left atrial appendage closure were urgently performed. Dabigatran was changed to warfarin again after the operation. She has had no recurrent thromboembolic event since then.

Cost-effectiveness of new oral anticoagulants and warfarin in atrial fibrillation from adverse events perspective / Análisis de costo-efectividad de los nuevos anticoagulantes orales y la warfarina en fibrilación auricular desde la perspectiva de los eventos adversos

Abstract Objective: new oral anticoagulants (apixaban, dabigatran and rivaroxaban) are the newest advance for stroke's risk reduction in atrial fibrillation. These are as effective as warfarin in preventing stroke/systemic embolism, but exists heterogenic outcomes as gastrointestinal hemorrhage, mortality reduction, minor and major haemorrhage (adverse events). Despite of this, there is a lack of cost-effectiveness models focused on adverse events. Methods: a cost-effectiveness analysis with a third payer perspective, interventions included were apixaban, dabigatran, warfarin and rivaroxaban. Discount rate of 3%, and 10 years of temporal horizon. The Markov model is an international, validated, and modified to assess better adverse events. Major assumptions, patients with mild and moderate stroke returns to oral anticoagulation, patients with moderate and severe hemorrhage do not returns to oral anticoagulation. Probabilities and QALYs, taken from a cost-effectiveness analysis published. Costs, information from a cohort of stroke patients. Software, TreeAge pro( and Excel(. Results: overall results, 1.48 QALYs, $17 916 USD for apixaban, 1.49 QALYs, $18 122 USD for dabigatran, 1.32 QALYs, $21 966 USD for warfarin and 1.24 QALYs, $24 547 USD for rivaroxaban. The ICER for apixaban compared to dabigatran was $12 988 USD. Negative ICER for warfarin and rivaroxaban, shows that are dominated alternatives (less benefits and more costs). Apixaban is cost-effective at 70% and dabigatran at 30% of iterations in the probabilistic sensitivity analysis. Conclusions: apixaban and dabigatran are cost-effective alternatives, apixaban is the most cost-effective alternative from adverse events perspective. Warfarin shows better results than rivaroxaban to prevent stroke in atrial fibrillation from adverse events perspective.

Resumen Introducción: los nuevos anticoagulantes orales (apixabán, dabigatrán y rivaroxabán) son el avance más reciente para la reducción del riesgo de accidente cerebrovascular en la fibrilación auricular. Estos son tan efectivos como la warfarina en la prevención del accidente cerebrovascular/embolia sistémica, pero existen resultados heterogéneos como hemorragia gastrointestinal, reducción de la mortalidad y hemorragia menor y mayor (eventos adversos). Pese a ello, se carece de modelos de costo-efectividad enfocados en eventos adversos. Materiales y métodos: se hizo un análisis de costo-efectividad con una perspectiva de tercer pagador, en el que se incluyeron intervenciones como apixabán, dabigatrán, warfarina y rivaroxabán. La tasa de descuento fue del 3% y 10 años de horizonte temporal. El modelo de Markov es internacional, validado y modificado para evaluar mejor eventos adversos. Las principales suposiciones, los pacientes con accidente cerebrovascular leve y moderado vuelven a la anticoagulación oral, los pacientes con hemorragia moderada y grave no regresan a la anticoagulación oral. Probabilidades y AVAC, tomados de un análisis de costo-efectividad publicado. Los costos, información de una cohorte de pacientes con accidente cerebrovascular. Software, TreeAge pro y Excel. Resultados: resultados generales, 1.48 QALYs, $ 17 916 USD para apixabán, 1.49 QALYs, $ 18 122USD para dabigatrán, 1.32 QALYs, $ 21 966 USD para warfarina y 1.24 QALYs, $ 24 547 USD para rivaroxabán. El ICER para apixabán en comparación con dabigatrán fue de $ 12 988 USD. El ICER negativo para warfarina y rivaroxabán muestra que son alternativas dominadas (menos beneficios y más costos). Apixabán es rentable en 70% y dabigatrán en 30% de las iteraciones en el análisis de sensibilidad probabilístico. Conclusión: apixabán y dabigatrán son costo-efectivos; apixabán es la alternativa más costo-efectiva desde la perspectiva de los eventos adversos. Warfarina mostró mejores resultados que rivaroxabán para prevenir accidentes cerebrovasculares en fibrilación auricular desde la perspectiva de los eventos adversos.

Resolution of Primary Aortic Thrombosis after Dabigatran therapy—A New Hope for the Rare and Old Disease

The primary aortic thrombosis (PAT) is an uncommon noncardiac cause of distal peripheral embolization to lower extremities. Also, this condition develops in the absence of extensive atherosclerosis of aorta or abnormal dilatation like aneurysm of the aorta. In most of the cases, there was either no or minimal atherosclerosis of the aorta. The disease can involve any part of the aorta, but in most of the cases, the thoracic aorta below the origin of the left subclavian artery followed by the infrarenal portion of the abdominal aorta was the most common site of involvement. In our case, there was extensive thrombosis starting from the lower part of the thoracic aorta extending across both the renal arteries up to the aortic bifurcation without any underlying aortic pathology or hypercoagulable disease. There are no guidelines for the management of the PAT, but our experience is based on few case series, case reports, and meta-analysis where there are variable success rate using conservative medical management, endovascular procedure, or surgical thrombectomy. Vitamin K antagonist was the drug of choice in all the cases as a part of conservative medical management or used to prevent recurrence after the endovascular or surgical procedure. We present a case of PAT where the use of dabigatran leads to complete resolution and prevented the recurrence of the disease during two-year follow-up, which is the first and unique case report of the literature.

Dabigatran and warfarin in nonvalvular atrial fibrillation or atrial flutter in outpatient clinic practice in Brazil / Dabigatrana e varfarina em pacientes com fibrilação atrial não valvar ou flutter em ambulatório especializado no Brasil

ABSTRACT Objectives: To compare warfarin and dabigatran for thromboembolic event prevention in patients with nonvalvular atrial fibrillation or atrial flutter. Methods: This was a retrospective cohort of participants with nonvalvular atrial fibrillation or atrial flutter using either warfarin or dabigatran in a reference center in Brazil. Results: There were 112 patients (mean age 65.5 years), with 55.3% using warfarin. The median duration of follow-up was 1.9 years for warfarin and 1.6 years for dabigatran (p = 0.167). Warfarin patients had a higher median of medical appointments per year (8.3 [6.8-10.4] vs 3.1 [2.3-4.2], p < 0.001) and the frequency of minor bleeding was more than four times higher (17.7% vs 4.0%, p = 0.035). Among patients with prior stroke, those using warfarin had 2.6 times more medical appointments for person-years of follow-up (8.5 vs 3.3). There was no major bleeding or embolic event during follow-up period. Conclusion: The dabigatran group had a lower frequency of minor bleeding and number of medical appointments than the warfarin group, without more embolic events or major bleeding.

RESUMO Objetivos: Comparar varfarina e dabigatrana para prevenção de eventos tromboembólicos em pacientes com fibrilação atrial não valvar ou flutter (FA). Métodos: Coorte retrospectiva de pacientes com FA em uso de varfarina ou dabigatrana em serviço especializado no Brasil. Resultados: Foram avaliados 112 pacientes (média idade 65,5), com 55,3% no grupo varfarina. A mediana do tempo de seguimento foi de 1,9 anos para o grupo varfarina e 1,6 para dabigatrana (p = 0,167). No grupo varfarina houve maior mediana de consultas médicas (CM) por ano (8,3[6,8-10,4] vs. 3,1[2,3-4,2], p < 0,001), com frequência de sangramento menor quatro vezes maior (17,7% vs. 4,0%, p = 0,035). Nos pacientes com acidente vascular cerebral isquêmico prévio, o grupo varfarina teve 2,6 vezes mais CM por pessoas-ano de seguimento (8,5 vs. 3,3). Não houve sangramento maior ou eventos embólicos no período de seguimento. Conclusão: Pacientes em uso de dabigatrana tiveram menor número de sangramento menor e CM que aqueles em uso de varfarina, sem aumentar eventos embólicos ou sangramentos maiores.

Practical guide to choosing dabigatran 150 mg twice daily or apixaban 5 mg twice daily for patients with atrial fibrillation / Journal of Rural Medicine

Based on previous reports, we propose a practical guide to choose dabigatran 150 mg twice daily or apixaban 5 mg twice daily for patients with atrial fibrillation. We recommend the use of dabigatran 150 mg twice daily for patients with atrial fibrillation who have a high risk of embolism (e.g., ischemic stroke on other oral anticoagulants, presence of left atrial appendage thrombus) and a low risk of bleeding. However, the prevalence of such patients with atrial fibrillation is considered low because patients with atrial fibrillation with a high risk of embolism usually have a high risk of bleeding. In most other patients with atrial fibrillation, the use of apixaban 5 mg twice daily should be considered.

Effect of low dose dabigatran etexilate on clinical efficacy of elderly patients with venous thromboembolism / 中国中西医结合急救杂志

Objective To observe the effect of low-dose dabigatran etexilate on the clinical efficacy of elderly patients with venous thromboembolism (VTE). Methods Seventy-five elderly (≥ 80 years old) VTE patients admitted to Cangzhou Central Hospital from October 2016 to June 2018 were enrolled, they were treated according to the VTE guidelines, and low dose dabigatran etexilate was the anticoagulant therapy selected, 110 mg once daily for 6 months. After treatment for 6 months, the thrombus regression situation with color Doppler ultrasonography;clinical efficacy was evaluated by clinical symptoms and ultrasonographic results, the changes in platelet count (PLT), coagulation parameters [international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (Fib)] before and after treatment were detected and the occurrence of adverse reactions were recorded and safety of drug was evaluated. Results There were no significant differences in PLT, INR and Fib before and after treatment [PLT (×109/L): 197.88±58.00 vs. 199.88±65.15, INR: 1.02±0.10 vs. 1.05±0.13, Fib (g/L): 2.89±0.67 vs. 2.84±0.70, all P > 0.05], the APTT after treatment was significantly prolonged compared with that before treatment (seconds:40.9±7.34 vs. 26.2±3.16), the difference being statistically significant (P < 0.05), the amount of APTT prolongation after treatment did not exceed 2 times [average (1.75±0.24) times] of the baseline value before treatment. The total effective rate of low-dose dabigatran etexilate for treatment of elderly patients with VTE for 6 months was 90.7% (68/75);no obvious adverse reactions occurred during the treatment. Conclusion Low-dose dabigatran etexilate for treatment of elderly patients with VTE is safe and effective without any obvious adverse reactions, and is worthy to be promoted for clinical use.

Trends and Current Status of Oral Anticoagulant Use in Hospitalized Patients in China / 中国药学杂志

OBJECTIVE: To investigate the trends and current status of oral anticoagulant (OAC) use in hospitalized patients. METHODS: OAC prescriptions of inpatients during 2012 to 2016 were extracted from the database of hospital prescription analysis cooperation program. The extracted prescriptions were restricted to hospitals which located in 5 major cities of China. The number of patients and cost of drugs were calculated and analyzed. RESULTS: A total of 258 276 prescriptions were extracted. The number of patients using OAC increased every year. Warfarin was the most frequently prescribed OAC, but the portion of warfarin decreased. Non vitamin-K antagonist anticoagulants (NOAC) including rivaroxaban increased rapidly. Imbalance existed between warfarin and NOAC on patient population and cost. The use of OAC differed by indications and specialists. CONCLUSION: The number of patients and cost of drugs increased every year while NOAC had taken a large portion of cost. Attention should be payed to the rationality of OAC use.

A national audit on the utilisation and documentation of dabigatran checklist for patients initiated on dabigatran

@#Background: Direct oral anticoagulants (DOACs) especially dabigatran, have gain popularity for their efficacy, fixed dosing and favourable safety profile. A dabigatran prescribing checklist has been prepared by the Ministry of Health, Malaysia (MOH) to ensure rational and safe prescribing of dabigatran. This study therefore aimed to audit the utilization and documentation of this checklist and use of dabigatran in the government healthcare facilities. Methods: This is a nationwide retrospective audit on the documentation of Dabigatran Prescribing and Dispensing Checklist for a period of two years from January 2013 till December 2014. Data from these Dabigatran Checklists (indication, dose, duration, renal function and adverse drug reactions encountered) were extracted by the pharmacist at MOH healthcare facilities. Results: A total of 52 out of 56 (92.9%) of MOH facilities complied to usage of checklist at their centres involving a total of 582 patients of which 569 (97.7%) patients were initiated on dabigatran for the approved indications. The recommended dose of dabigatran was used correctly in 501 (99.6%) of patients. Reason for switching to DOACs use was only documented in 76.7% (131/171) of patients. The most common reason for switching from warfarin was poor INR control (n=39), history of bleeding/overwarfarinisation (n=22) and unable to attend regular INR clinic (n=21). There were 75 cases of adverse events reported. The most common adverse event reported were abdominal discomfort (n=10) followed by gum bleeding (n=9) and dizziness (n=5). Conclusions: Compliance to the dabigatran check list was high with 70% of patients prescribed the appropriate dosing.