RESUMEN
OBJECTIVES: Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used. We sought to compare extracorporeal membrane oxygenation circuit thrombosis and bleeding-related outcomes in respiratory failure patients receiving either unfractionated heparin or bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation support. DESIGN: Retrospective cohort study. SETTING: Single-center, cardiothoracic ICU. PATIENTS: Consecutive patients requiring venovenous extracorporeal membrane oxygenation who were maintained on anticoagulation between 2013 and 2020. INTERNVENTIONS: IV bivalirudin or IV unfractionated heparin. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were the presence of extracorporeal membrane oxygenation in-circuit-related thrombotic complications and volume of blood products administered during extracorporeal membrane oxygenation duration. One hundred sixty-two patients receiving unfractionated heparin were compared with 133 patients receiving bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation. In patients receiving bivalirudin, there was an overall decrease in the number of extracorporeal membrane oxygenation circuit thrombotic complications (p < 0.005) and a significant increase in time to circuit thrombosis (p = 0.007). Multivariable Cox regression found that heparin was associated with a significant increase in risk of clots (Exp[B] = 2.31, p = 0.001). Patients who received bivalirudin received significantly less volume of packed RBCs, fresh frozen plasma, and platelet transfusion (p < 0.001 for each). There was a significant decrease in the number major bleeding events in patients receiving bivalirudin, 40.7% versus 11.7%, p < 0.001. CONCLUSIONS: Patients receiving bivalirudin for systemic anticoagulation on venovenous extracorporeal membrane oxygenation experienced a decrease in the number of extracorporeal membrane oxygenation circuit-related thrombotic events as well as a significant decrease in volume of blood products administered.
Asunto(s)
Anticoagulantes/uso terapéutico , Antitrombinas/uso terapéutico , Oxigenación por Membrana Extracorpórea/efectos adversos , Hemorragia/inducido químicamente , Heparina/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Trombosis/prevención & control , Adulto , Anticoagulantes/efectos adversos , Antitrombinas/efectos adversos , Transfusión de Eritrocitos , Femenino , Heparina/efectos adversos , Hirudinas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/efectos adversos , Plasma , Transfusión de Plaquetas , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Trombosis/etiologíaRESUMEN
BACKGROUND: The term Direct Oral Anticoagulants (DOACs) refers to a group of drugs that inhibit factor Xa or thrombin. Even though their use for treating different thrombotic or prothrombotic conditions is increasing recently, there is no compelling evidence indicating that those medications are safe in all antiphospholipid syndrome (APS) patients. METHODOLOGY: To address this issue, specialists from the Antiphospholipid Syndrome Committee of the Brazilian Society of Rheumatology performed a comprehensive review of the literature regarding DOACs use in APS to answer the three following questions: (1) potential mechanisms of action of these drugs that could be relevant to APS pathogenesis, (2) DOACs interference on lupus anticoagulant testing, and (3) the efficacy of DOACs in APS. POSITION STATEMENT: After critically reviewing the relevant evidence, the authors formulated 8 Position Statements about DOACs use in APS. CONCLUSION: DOACs should not be routinely used in APS patients, especially in those with a high-risk profile (triple positivity to aPL, arterial thrombosis, and recurrent thrombotic events). In addition, DOACs interferes with LA testing, leading to false-positive results in patients investigating APS.
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Comités Consultivos , Síndrome Antifosfolípido/tratamiento farmacológico , Antitrombinas/uso terapéutico , Consenso , Administración Oral , Antitrombinas/efectos adversos , Antitrombinas/farmacología , Brasil , Contraindicaciones de los Medicamentos , Interacciones Farmacológicas , Sustitución de Medicamentos , Humanos , Inhibidor de Coagulación del Lupus/análisis , Estudios Observacionales como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Reumatología , Sociedades Médicas , Trombosis/tratamiento farmacológico , Resultado del TratamientoAsunto(s)
Aneurisma Coronario/terapia , Síndrome Mucocutáneo Linfonodular/complicaciones , Infarto del Miocardio/terapia , Anticoagulantes/uso terapéutico , Antitrombina III/análisis , Antitrombina III/uso terapéutico , Antitrombinas/uso terapéutico , Biomarcadores/sangre , Niño , Toma de Decisiones Clínicas , Protocolos Clínicos , Aneurisma Coronario/etiología , Fibrinógeno/análisis , Fibrinolíticos/uso terapéutico , Heparina/uso terapéutico , Humanos , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
INTRODUCTION: The interaction between anticoagulants and platelet function is complex. Previous publications showed mixed results regarding the role of heparins in platelet aggregation. On the other hand, the direct thrombin inhibitor (DTI) dabigatran might enhance the risk of myocardial infarction in patients with atrial fibrillation, which could be related to increased platelet aggregability. METHODS: This was a prospective, interventional study of patients with chronic coronary artery disease (CAD) taking low-dose aspirin. The objective of the current study was to compare the effects of dabigatran versus enoxaparin on platelet aggregability. Subjects initially were on orally administered dabigatran for 5 days followed by subcutaneously administered enoxaparin after a 30-day washout period. Platelet function was assessed at baseline and after each intervention by multiple electrode aggregometry (MEA-ASPI) (primary endpoint), serum thromboxane B2 (TXB2), VerifyNow Aspirin™, and coagulation tests (secondary endpoints). RESULTS: Compared to baseline MEA-ASPI values, dabigatran increased platelet aggregation while enoxaparin decreased platelet aggregation (+ 5 U ± 24.1 vs - 6 U ± 22.2, respectively, p = 0.012). The TXB2 assay showed the same pattern (+ 2 pg/ml for dabigatran vs - 13 pg/ml for enoxaparin, p = 0.011). None of the additional tests showed significant differences between the groups. Individually, compared to baseline TXB2 results, enoxaparin significantly decreased platelet activation [33 (16.5-95) pg/mL vs 20 (10-52) pg/mL, respectively, p = 0.026], but no significant differences were observed with dabigatran. CONCLUSIONS: DTI and anti-Xa drugs exert opposite effects on platelet function. A significant decrease in platelet activation through COX1 (also known as prostaglandin G/H synthase 1) was observed with enoxaparin, but no significant differences in platelet function were observed with dabigatran. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02389582.
Asunto(s)
Antitrombinas/uso terapéutico , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Dabigatrán/uso terapéutico , Enoxaparina/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Agregación Plaquetaria/efectos de los fármacos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Tecnologia: Inibidores Diretos do Fator Xa (IDFXa) Rivaroxabana, Apixabana, Edoxabana e Inibidores Diretos da Trombina (IDT) Dabigatrana todos são anticoagulantes orais diretos (DOAC). Indicação: tratamento e prevenção de fenômenos tromboembólicos. Pergunta: Para tratamento de tromboembolismo pulmonar (TEP) e trombose venosa profunda (TVP), os DOAC são mais eficazes e seguros que a anticoagulação tradicional com heparina e varfarina? Métodos: Levantamento bibliográfico na base de dados Pubmed seguindo estratégias de buscas predefinidas. Avaliação da qualidade metodológica das revisões sistemáticas com a ferramenta Assessing the Methodological Quality of Systematic Reviews (AMSTAR). Resultados: Foram selecionadas e incluídas 4 revisões sistemáticas. Conclusão: Na maioria dos estudos incluídos, os DOAC demonstraram eficácia e segurança similar à anticoagulação tradicional com heparina e varfarina para tratamento de TEP e TVP. Em um estudo, o risco de TVP recorrente foi menor no tratamento de IDFXa (por menos 3 meses de tratamento) e de episódios de sangramento maior foi menor no tratamento de IDT e IDFXa (por mais 3 meses de tratamento)
Technology: Direct Factor Xa Inhibitors (DFXaI) - Rivaroxaban, Apixaban, Edoxaban and Direct Thrombin Inhibitors (DTI) - Dabigatran - all are direct oral anticoagulants (DOAC). Indication: treatment and prevention of thromboembolic phenomena. Question: For treatment of pulmonary thromboembolism (PTE) and deep vein thrombosis (DVT), are DOACs more effective and safer than traditional anticoagulation with heparin and warfarin? Methods: Bibliographic survey in the Pubmed database following predefined search strategies. Evaluation of the methodological quality of systematic reviews with the tool Assessing the Methodological Quality of Systematic Reviews (AMSTAR). Results: 4 systematic reviews were selected and included. Conclusion: In most of the included studies, DOAC demonstrated similar efficacy and safety to traditional anticoagulation with heparina and warfarin for the treatment of PTE and DVT. In one study, the risk of recurrent DVT was lower in the treatment of DFXaI (for at least 3 months of treatment) and of major bleeding episodes was lower in the treatment of DTI and DFXaI (for another 3 months of treatment)
Asunto(s)
Humanos , Embolia Pulmonar/tratamiento farmacológico , Warfarina/uso terapéutico , Heparina/uso terapéutico , Trombosis de la Vena/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéutico , Anticoagulantes/uso terapéutico , Trombina/uso terapéutico , Antitrombinas/uso terapéutico , Resultado del Tratamiento , Rivaroxabán/uso terapéutico , Dabigatrán/uso terapéuticoRESUMEN
BACKGROUND: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with high rates of death, ischemic stroke and systemic embolism (SE). There is scarce information about clinical characteristics and use of anti-thrombotic therapies in Chilean patients with non-valvular AF. AIM: To describe the characteristics and 1-year outcomes of patients with recently diagnosed AF recruited in Chile into the prospective global GARFIELD-AF registry. MATERIAL AND METHODS: Between 2011-2016, we prospectively registered information of 971 patients recruited at 15 centers, 85% of them from the public system and 15% from the private sector. Demographics, clinical characteristics and use of antithrombotic therapies were recorded for all patients. Adverse clinical outcomes were analyzed in 711 patients with 1-year follow-up. RESULTS: The mean age was 71.5 years (66-79), 50% were men. Mean CHAD2S2 Vasc and HAS BLED scores for stroke risk were 3.3 (2.0-4.0) and 1.5 (1.0-2.0) respectively. Oral anticoagulants were prescribed in 82% of patients. Seventy percent received Vitamin K antagonists, 10% novel direct anticoagulants or antiplatelet therapy and only 8% did not receive any antithrombotic therapy. Mean time in optimal therapeutic range (an international normalized ratio of 2 to 3), was achieved in only 40.7% (23.0-54.8) of patients receiving Vitamin K antagonists. One year rates of death, stroke/systemic embolism and bleeding were 4.75 (3.36-6.71), 2.40 (1.47-3.92) and 1.64% (0.91-2.97) per 100 person-years. Ischemic stroke occurred in 1.8% and hemorrhagic stroke in 0.8% of patients at 1-year of follow up. CONCLUSIONS: Although the use of vitamin K antagonists at baseline was high, the mean time in optimal therapeutic range was low. Mortality and stroke rates are higher than those reported in other contemporary registries.
Asunto(s)
Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Fibrinolíticos/uso terapéutico , Anciano , Antitrombinas/uso terapéutico , Fibrilación Atrial/complicaciones , Chile/epidemiología , Inhibidores del Factor Xa/uso terapéutico , Femenino , Humanos , Masculino , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Estudios Prospectivos , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Factores de Tiempo , Vitamina K/antagonistas & inhibidoresRESUMEN
Resumen: Los anticoagulantes orales clásicos del tipo cumarinas han estado disponibles para uso clínico por más de medio siglo. Tienen gran eficacia para tratar o prevenir trombosis y tromboembolias, y son drogas cuyo uso ha aumentado con el mejor conocimiento clínico, el aumento de los factores de riesgo y el envejecimiento de la población. Entre sus desventajas se incluyen la alta variabilidad de su efecto en cada sujeto y entre individuos, la influencia del nivel de ingesta de vitamina K, la necesidad de control periódico del nivel de anticoagulación, su interacción con múltiples drogas. Si bien, el rango terapéutico está estandarizado, es estrecho, haciendo que el tiempo en rango terapéutico sea de ≈ 60%. Por estas limitaciones, se han creado nuevos anticoagulantes orales (NACOs), siendo progresivamente aprobados para uso clínico por agencias internacionales. Genéricamente, son de 2 tipos: inhibidores selectivos de trombina (dabigatrán) o de FXa (rivaroxabán, apixabán, edoxabán y betrixabán). Los NACOs se caracterizan por su dosificación una o dos veces al día, rapidez de acción, corta vida media en la circulación, predictibilidad de su efecto, dosis preestablecidas, sin necesidad de control periódico y con escasa o nula interacción con otras drogas. Estas ventajas no se han traducido en la mayoría de los ensayos en un superior efecto antitrombótico o menor riesgo de sangrado, y en su mayoría (salvo dabigatrán) carecen de antídoto específico demostrado.
Abstracts: Vitamin K inhibitors, coumarins, have been used for more than 50 years with no dispute by other drugs. Coumarins have demonstrated great efficacy in the treatment and prophylaxis of thrombotic and thromboembolic disorders, and their use has increased progressively with the advance of clinical knowledge as well as the increase of risk factors and aging of the population. Limitations of coumarins include great variability intra and inter-individuals, the influence of foods rich in vitamin K, the need for periodical assessment of the anticoagulant level and drug interactions. The therapeutic range is standardized using the INR (International Normalized Ratio). However, the therapeutic window is narrow, with frequent periods of either over or under-dosing, with the concomitant increase of bleeding and thrombotic risks, respectively. Long-term accredited anticoagulant clinics and clinical trials report that, at best, only ≈60% of time in treatment the patients are within the therapeutic range. These limitations have created the need for new oral anticoagulants (NOACs), and several of them have been approved for clinical use by international agencies after exhaustive and specific clinical trials. Generically, NACOs are belong in two types: selective inhibitors of thrombin (dabigatran) or FXa (rivaroxaban, apixaban, edoxaban and betrixaban). NOACs are prescribed once or twice daily, the onset of action is very fast, have a low T1/2 in the circulation, their effects are highly predictable, doses are pre-established, do not need laboratory control and have a low rate of interaction with other drugs. Despite these advantages most clinical trials have shown NOACs to be not inferior with respect to coumarin. However, NOACs have no clear advantages over warfarin in antithrombotic effect or bleeding reduction. Furthermore, most of them (except dabigatran) have no specific antidotes yet.
Asunto(s)
Humanos , Antitrombinas/administración & dosificación , Inhibidores del Factor Xa/administración & dosificación , Anticoagulantes/administración & dosificación , Antitrombinas/uso terapéutico , Administración Oral , Inhibidores del Factor Xa/uso terapéutico , Anticoagulantes/uso terapéuticoRESUMEN
Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with high rates of death, ischemic stroke and systemic embolism (SE). There is scarce information about clinical characteristics and use of anti-thrombotic therapies in Chilean patients with non-valvular AF. Aim: To describe the characteristics and 1-year outcomes of patients with recently diagnosed AF recruited in Chile into the prospective global GARFIELD-AF registry. Material and Methods: Between 2011-2016, we prospectively registered information of 971 patients recruited at 15 centers, 85% of them from the public system and 15% from the private sector. Demographics, clinical characteristics and use of antithrombotic therapies were recorded for all patients. Adverse clinical outcomes were analyzed in 711 patients with 1-year follow-up. Results: The mean age was 71.5 years (66-79), 50% were men. Mean CHAD2S2 Vasc and HAS BLED scores for stroke risk were 3.3 (2.0-4.0) and 1.5 (1.0-2.0) respectively. Oral anticoagulants were prescribed in 82% of patients. Seventy percent received Vitamin K antagonists, 10% novel direct anticoagulants or antiplatelet therapy and only 8% did not receive any antithrombotic therapy. Mean time in optimal therapeutic range (an international normalized ratio of 2 to 3), was achieved in only 40.7% (23.0-54.8) of patients receiving Vitamin K antagonists. One year rates of death, stroke/systemic embolism and bleeding were 4.75 (3.36-6.71), 2.40 (1.47-3.92) and 1.64% (0.91-2.97) per 100 person-years. Ischemic stroke occurred in 1.8% and hemorrhagic stroke in 0.8% of patients at 1-year of follow up. Conclusions: Although the use of vitamin K antagonists at baseline was high, the mean time in optimal therapeutic range was low. Mortality and stroke rates are higher than those reported in other contemporary registries.
Asunto(s)
Humanos , Masculino , Femenino , Anciano , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/epidemiología , Fibrinolíticos/uso terapéutico , Pronóstico , Fibrilación Atrial/complicaciones , Factores de Tiempo , Vitamina K/antagonistas & inhibidores , Inhibidores de Agregación Plaquetaria/uso terapéutico , Chile/epidemiología , Sistema de Registros , Antitrombinas/uso terapéutico , Estudios Prospectivos , Factores de Riesgo , Medición de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/epidemiología , Inhibidores del Factor Xa/uso terapéuticoRESUMEN
Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.
Asunto(s)
Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Antitrombinas/uso terapéutico , Heparina/efectos adversos , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Trombosis/prevención & control , Anticoagulantes/inmunología , Heparina/inmunología , Humanos , Factor Plaquetario 4/inmunología , Trombocitopenia/inmunología , Trombosis de la Vena/prevención & controlRESUMEN
La trombocitopenia inducida por heparina (TIH) es una reacción adversa inmunológica mediada por la formación de anticuerpos contra el complejo heparina-factor plaquetario 4 (FP4), caracterizada por la presencia de trombocitopenia y la asociación paradojal de trombosis arterial o venosa. Es una complicación poco frecuente pero grave del uso de cualquier tipo de heparina. En tratados con procedimientos cardiovasculares como intervención coronaria percutánea y cirugía de revascularización cardiaca, la prevalencia de anticuerpos es significativamente mayor que en otros escenarios clínicos. El reconocimiento de las características clínicas y de laboratorio permite la suspensión inmediata de la heparina y la instauración de tratamiento anticoagulante alternativo, para evitar la progresión y formación de nuevos trombos y sus complicaciones. En la presente revisión se resumen las diferentes alternativas terapéuticas para la TIH, en particular los anticoagulantes orales directos (DOACS) como el dabigatran, rivaroxaban y apixaban que pueden proporcionar una nueva opción para el tratamiento de TIH.
Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.
Asunto(s)
Humanos , Trombocitopenia/inducido químicamente , Trombocitopenia/tratamiento farmacológico , Heparina/efectos adversos , Antitrombinas/uso terapéutico , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Trombocitopenia/inmunología , Trombosis/prevención & control , Factor Plaquetario 4/inmunología , Heparina/inmunología , Trombosis de la Vena/prevención & control , Anticoagulantes/inmunologíaAsunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antitrombinas/efectos adversos , Dabigatrán/efectos adversos , Inhibidores del Factor Xa/efectos adversos , Factor Xa/uso terapéutico , Hemorragia/tratamiento farmacológico , Pirazoles/efectos adversos , Piridinas/efectos adversos , Piridonas/efectos adversos , Proteínas Recombinantes/uso terapéutico , Rivaroxabán/efectos adversos , Tiazoles/efectos adversos , Administración Oral , Anticuerpos Monoclonales Humanizados/farmacología , Antitrombinas/uso terapéutico , Pérdida de Sangre Quirúrgica/prevención & control , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/terapia , Ensayos Clínicos como Asunto , Dabigatrán/antagonistas & inhibidores , Dabigatrán/inmunología , Dabigatrán/uso terapéutico , Aprobación de Drogas , Urgencias Médicas , Factor Xa/farmacología , Inhibidores del Factor Xa/uso terapéutico , Hemorragia/inducido químicamente , Humanos , Pirazoles/antagonistas & inhibidores , Pirazoles/uso terapéutico , Piridinas/antagonistas & inhibidores , Piridinas/uso terapéutico , Piridonas/antagonistas & inhibidores , Piridonas/uso terapéutico , Proteínas Recombinantes/farmacología , Rivaroxabán/antagonistas & inhibidores , Rivaroxabán/uso terapéutico , Tiazoles/antagonistas & inhibidores , Tiazoles/uso terapéutico , Estados Unidos , United States Food and Drug AdministrationRESUMEN
Atrial fibrillation (AF) is associated with an increased risk of stroke. AF-related strokes cause greater disability and mortality than those in patients without AF, and are associated with a significant clinical and economic burden in Mexico. Antithrombotic therapy reduces stroke risk in patients with AF and is recommended for all patients except those classified as having a low stroke risk. However, its use is suboptimal all around the world; one study showed that only 4 % of Mexican patients with AF who presented with ischemic stroke were in the therapeutic range for anticoagulation. Vitamin K antagonists (VKAs) such as warfarin or acenocoumarin have long been the only oral anticoagulants for stroke prevention in AF. Although effective, VKAs have disadvantages, including the need for regular coagulation monitoring and dose adjustment. Interactions with numerous common medications and foods contribute to the risk of serious bleeding and thrombotic events in VKA-treated patients. Thus novel oral anticoagulants (NOACs), more properly called direct oral anticoagulants (DOACs), such as dabigatran etexilate, rivaroxaban, apixaban, and edoxaban (not available in Mexico), have been developed. These offer the convenience of fixed-dose treatment without the need for monitoring, and have few drug or food interactions. Pivotal phase III trials have demonstrated that these agents are at least as effective as warfarin in preventing stroke and are associated with a reduced risk of intracranial hemorrhage. With apixaban approved in Mexico in April 2013, clinicians now have the choice of three novel DOACs as alternatives to warfarin. However, it is yet to be established which of these agents should be the first choice, and treatment decisions are likely to depend on the individual patient's characteristics.
Asunto(s)
Anticoagulantes/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Medicina Basada en la Evidencia , Medicina de Precisión , Accidente Cerebrovascular/prevención & control , Administración Oral , Anticoagulantes/administración & dosificación , Anticoagulantes/efectos adversos , Antitrombinas/administración & dosificación , Antitrombinas/efectos adversos , Antitrombinas/uso terapéutico , Fibrilación Atrial/fisiopatología , Dabigatrán/administración & dosificación , Dabigatrán/efectos adversos , Dabigatrán/uso terapéutico , Esquema de Medicación , Drogas en Investigación/administración & dosificación , Drogas en Investigación/efectos adversos , Drogas en Investigación/uso terapéutico , Humanos , México , Guías de Práctica Clínica como Asunto , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Piridinas/administración & dosificación , Piridinas/efectos adversos , Piridinas/uso terapéutico , Piridonas/administración & dosificación , Piridonas/efectos adversos , Piridonas/uso terapéutico , Factores de Riesgo , Rivaroxabán/administración & dosificación , Rivaroxabán/efectos adversos , Rivaroxabán/uso terapéutico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Tiazoles/administración & dosificación , Tiazoles/efectos adversos , Tiazoles/uso terapéutico , Vitamina K/antagonistas & inhibidores , Vitamina K/metabolismoRESUMEN
OBJECTIVES: Dabigatran is a direct thrombin inhibitor shown to be an effective alternative to warfarin in patients with non-valvular atrial fibrillation (AF). We evaluated the use of dabigatran in patients with bioprosthetic mitral and/or aortic valve replacement and AF. METHODS: We selected 34 and randomized 27 patients in a 1:1 ratio to receive dabigatran or warfarin. The primary endpoint was the presence of a new intracardiac thrombus at 90 days, by transesophageal echocardiogram (TEE). Secondary endpoints included the development of dense spontaneous echo contrast (SEC) and incidence of stroke (ischemic or hemorrhagic), myocardium infarction, valve thrombosis and peripheral embolic events. RESULTS: The trial was terminated prematurely because of low enrollment. There were 27 patients in total: 15 patients placed in the dabigatran group and 12 in the warfarin group. After 90 days, one patient (8.3 %) in the warfarin group and none in the dabigatran group had developed a new intracardiac thrombus. In the dabigatran group, two patients (13.3 %) developed dense SEC versus one patient (8.3 %) in the warfarin group. In the warfarin group, one patient (8.3 %) presented ischemic stroke, and none did in the dabigatran group. We observed no cases of hemorrhagic stroke, valve thrombosis, embolic events or myocardial infarction in either group throughout the study. However, one patient (6.7 %) in the dabigatran group had a fully recovered transient ischemic attack and one patient in the warfarin group died of heart failure. CONCLUSIONS: The use of dabigatran appears to be similar to warfarin in preventing the formation of intracardiac thrombus. TRIAL REGISTRATION: Clinicaltrials.gov NCT01868243.
Asunto(s)
Antitrombinas/uso terapéutico , Dabigatrán/uso terapéutico , Cardiopatías/tratamiento farmacológico , Trombosis/tratamiento farmacológico , Warfarina/uso terapéutico , Adolescente , Adulto , Antitrombinas/administración & dosificación , Antitrombinas/efectos adversos , Fibrilación Atrial/tratamiento farmacológico , Bioprótesis , Anuloplastia de la Válvula Cardíaca , Dabigatrán/administración & dosificación , Dabigatrán/efectos adversos , Femenino , Cardiopatías/fisiopatología , Cardiopatías/terapia , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Trombosis/fisiopatología , Trombosis/terapia , Resultado del Tratamiento , Warfarina/administración & dosificación , Warfarina/efectos adversos , Adulto JovenRESUMEN
The results of randomized trials and observational studies make a strong argument for the use of bivalirudin rather than heparin plus systematic glycoprotein (GP) IIb/IIIa inhibitors for the great majority of patients undergoing percutaneous coronary interventions (PCI). However, there is no doubt that the benefit observed with bivalirudin was achieved because of the major bleeding complications with heparin plus GP IIb/IIIa inhibitors. Therefore, if we diminish bleeding complications by eliminating the systematic utilization of GP IIb/IIIa inhibitors, there would be a lesser benefit with the use of bivalirudin. When this latter drug was compared with unfractionated heparin alone there was no benefit in ischemic complications but a decrease in major bleeding complications with bivalirudin. However, a very recent meta-analysis shed more insights on the utilization of bivalirudin versus heparin regimens during PCI. Findings from this meta-analysis suggest that routine use of bivalirudin offers little advantage over heparin among PCI patients. In a detailed analysis of some randomized trials and observational studies with bivalirudin in non-ST-segment elevation acute coronary syndrome patients done by myself and published almost 4 years ago in this journal, I rendered some reflections on the future widespread use of bivalirudin. "In the setting of PCI and in the absence of GP IIb/IIIa inhibitors, bivalirudin did not offer any beneficial effect in the incidence of the composite end points when compared with heparin. For now, in real world practice, one would probably choose a well-known cheaper drug that has already passed the test of time, heparin. There may be reinforcement in the sole utilization of heparin confining GP IIb/IIIa inhibitors and other intravenous antithrombotics to bailout therapy for periprocedural PCI complications in acute coronary syndrome patients." Therefore, is it the beginning of a new era with bivalirudin or is it a welcome back to an old friend, heparin? Indeed, after more than two decades, it is always good to welcome back an old friend, unfractionated heparin.
Asunto(s)
Síndrome Coronario Agudo/terapia , Anticoagulantes/uso terapéutico , Antitrombinas/uso terapéutico , Heparina/uso terapéutico , Fragmentos de Péptidos/uso terapéutico , Intervención Coronaria Percutánea/métodos , Hirudinas , Humanos , Proteínas Recombinantes/uso terapéuticoRESUMEN
BACKGROUND: Dabigatran is a novel oral anti-coagulant (NOAC) that reduces risk of stroke in patients with non-valvular atrial fibrillation (NVAF). It does not require routine monitoring with laboratory testing which may have an adverse impact on adherence. We aimed to describe adherence to dabigatran in the first year after initiation and assess the association between non-adherence to dabigatran and clinical outcomes in a large integrated healthcare system. METHODS: We studied a national cohort of 5,376 patients with NVAF, initiated on dabigatran between October-2010 and September-2012 at all Veterans Affairs hospitals. Adherence to dabigatran was calculated as proportion of days covered (PDC) and association between PDC and outcomes was assessed using standard regression techniques. RESULTS: Mean age of the study cohort was 71.3 ± 9.7 years; 98.3% were men and mean CHADS2 score was 2.4 ± 1.2 (mean CHA2DS2VASc score 3.2 ± 1.4). Median PDC was 94% (IQR 76%-100%; mean PDC 84% ± 22%) over a median follow-up of 244 days (IQR 140-351). A total of 1,494 (27.8%) patients had a PDC <80% and were classified as non-adherent. After multivariable adjustment, lower adherence was associated with increased risk for combined all-cause mortality and stroke (HR 1.13, 95% CI 1.07-1.19 per 10% decrease in PDC). Adherence to dabigatran was not associated with non-fatal bleeding or myocardial infarction. CONCLUSIONS: In the year after initiation, adherence to dabigatran for a majority of patients is very good. However, 28% of patients in our cohort had poor adherence. Furthermore, lower adherence to dabigatran was associated with increased adverse outcomes. Concerted efforts are needed to optimize adherence to NOACs.
Asunto(s)
Antitrombinas/uso terapéutico , Bencimidazoles/uso terapéutico , Cumplimiento de la Medicación/estadística & datos numéricos , Infarto del Miocardio/prevención & control , Accidente Cerebrovascular/prevención & control , beta-Alanina/análogos & derivados , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Estudios de Cohortes , Dabigatrán , Femenino , Hemorragia/inducido químicamente , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Resultado del Tratamiento , Estados Unidos , United States Department of Veterans Affairs , beta-Alanina/uso terapéuticoRESUMEN
Dabigatran is an oral anticoagulant from the class of the direct thrombin inhibitors, indicated for prevention of thromboembolic events in patients with non valvular atrial fibrillation. Unlike warfarin, dabigatran has no known antidote. Hemodialysis has been suggested as a method for removing dabigatran and thereby reducing its anticoagulant effect. We report the case of a patient with a known history of atrial fibrillation, treated with dabigatran, who was admitted for emergency abdominal surgery. At six hours after the last dose received, coagulation studies were altered. In absence of an antidote to reverse its effects, it was decided to perform hemodialysis. After three hours of dialysis coagulation parameters were improved and the patient underwent surgery without showing abnormal bleeding during surgery or in the postoperative period.
Asunto(s)
Antitrombinas/sangre , Bencimidazoles/sangre , Diverticulitis/cirugía , Urgencias Médicas , Diálisis Renal , beta-Alanina/análogos & derivados , Anciano de 80 o más Años , Antitrombinas/uso terapéutico , Fibrilación Atrial/sangre , Fibrilación Atrial/tratamiento farmacológico , Bencimidazoles/uso terapéutico , Pruebas de Coagulación Sanguínea , Dabigatrán , Diverticulitis/sangre , Humanos , Masculino , beta-Alanina/sangre , beta-Alanina/uso terapéuticoRESUMEN
El dabigatrán es un nuevo inhibidor directo de la trombina, de administración oral, empleado para la prevención de eventos tromboembólicos en pacientes con fibrilación auricular no valvular. A diferencia de la warfarina, no se dispone de un antídoto conocido. La hemodiálisis ha sido sugerida como un método para remover el dabigatrán y reducir el efecto anticoagulante. Se presenta el caso de un paciente con antecedente de fibrilación auricular y medicado con dabigatrán, que fue admitido en el hospital para una cirugía abdominal de urgencia. A las seis horas de la última dosis recibida, los estudios de coagulación mostraban alteración. Ante la falta de antídoto para revertir los efectos, se decidió realizar hemodiálisis. Luego de tres horas de diálisis los parámetros de coagulación tendieron a normalizarse y el paciente fue operado sin presentar hemorragias anormales durante la cirugía o en el postoperatorio.
Dabigatran is an oral anticoagulant from the class of the direct thrombin inhibitors, indicated for prevention of thromboembolic events in patients with non valvular atrial fibrillation. Unlike warfarin, dabigatran has no known antidote. Hemodialysis has been suggested as a method for removing dabigatran and thereby reducing its anticoagulant effect. We report the case of a patient with a known history of atrial fibrillation, treated with dabigatran, who was admitted for emergency abdominal surgery. At six hours after the last dose received, coagulation studies were altered. In absence of an antidote to reverse its effects, it was decided to perform hemodialysis. After three hours of dialysis coagulation parameters were improved and the patient underwent surgery without showing abnormal bleeding during surgery or in the postoperative period.
Asunto(s)
Anciano de 80 o más Años , Humanos , Masculino , Antitrombinas/sangre , Bencimidazoles/sangre , Diverticulitis/cirugía , Urgencias Médicas , Diálisis Renal , beta-Alanina/análogos & derivados , Antitrombinas/uso terapéutico , Fibrilación Atrial/sangre , Fibrilación Atrial/tratamiento farmacológico , Pruebas de Coagulación Sanguínea , Bencimidazoles/uso terapéutico , Dabigatrán , Diverticulitis/sangre , beta-Alanina/sangre , beta-Alanina/uso terapéuticoRESUMEN
BACKGROUND: Chronic anticoagulation with vitamin K antagonists (VKAs) prevents ischaemic stroke and systemic embolism in people with non-valvular atrial fibrillation (AF) but dose adjustment, coagulation monitoring and bleeding limits its use. Direct thrombin inhibitors (DTIs) are under investigation as potential alternatives. OBJECTIVES: To assess (1) the comparative efficacy of long-term anticoagulation using DTIs versus VKAs on vascular deaths and ischaemic events in people with non-valvular AF, and (2) the comparative safety of chronic anticoagulation using DTIs versus VKAs on (a) fatal and non-fatal major bleeding events including haemorrhagic strokes, (b) adverse events other than bleeding and ischaemic events that lead to treatment discontinuation and (c) all-cause mortality in people with non-valvular AF. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (July 2013), the Cochrane Central Register of Controlled Trials (CENTRAL), (The Cochrane Library, May 2013), MEDLINE (1950 to July 2013), EMBASE (1980 to October 2013), LILACS (1982 to October 2013) and trials registers (September 2013). We also searched the websites of clinical trials and pharmaceutical companies and handsearched the reference lists of articles and conference proceedings. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing DTIs versus VKAs for prevention of stroke and systemic embolism in people with non-valvular AF. DATA COLLECTION AND ANALYSIS: All three review authors independently performed data extraction and assessment of risk of bias. Primary analyses compared all DTIs combined versus warfarin. We performed post hoc analyses excluding ximelagatran because this drug was withdrawn from the market owing to safety concerns. MAIN RESULTS: We included eight studies involving a total of 27,557 participants with non-valvular AF and one or more risk factors for stroke; 26,601 of them were assigned to standard doses groups and included in the primary analysis. The DTIs: dabigatran 110 mg twice daily and 150 mg twice daily (three studies, 12,355 participants), AZD0837 300 mg once per day (two studies, 233 participants) and ximelagatran 36 mg twice per day (three studies, 3726 participants) were compared with the VKA warfarin (10,287 participants). Overall risk of bias and statistical heterogeneity of the studies included were low.The odds of vascular death and ischaemic events were not significantly different between all DTIs and warfarin (odds ratio (OR) 0.94, 95% confidence interval (CI) 0.85 to 1.05). Sensitivity analysis by dose of dabigatran on reduction in ischaemic events and vascular mortality indicated that dabigatran 150 mg twice daily was superior to warfarin although the effect estimate was of borderline statistical significance (OR 0.86, 95% CI 0.75 to 0.99). Sensitivity analyses by other factors did not alter the results. Fatal and non-fatal major bleeding events, including haemorrhagic strokes, were less frequent with the DTIs (OR 0.87, 95% CI 0.78 to 0.97). Adverse events that led to discontinuation of treatment were significantly more frequent with the DTIs (OR 2.18, 95% CI 1.82 to 2.61). All-cause mortality was similar between DTIs and warfarin (OR 0.91, 95% CI 0.83 to 1.01). AUTHORS' CONCLUSIONS: DTIs were as efficacious as VKAs for the composite outcome of vascular death and ischaemic events and only the dose of dabigatran 150 mg twice daily was found to be superior to warfarin. DTIs were associated with fewer major haemorrhagic events, including haemorrhagic strokes. Adverse events that led to discontinuation of treatment occurred more frequently with the DTIs. We detected no difference in death from all causes.
Asunto(s)
Antitrombinas/uso terapéutico , Fibrilación Atrial/complicaciones , Embolia/prevención & control , Accidente Cerebrovascular/prevención & control , Vitamina K/antagonistas & inhibidores , Amidinas/uso terapéutico , Antitrombinas/efectos adversos , Azetidinas/efectos adversos , Azetidinas/uso terapéutico , Bencimidazoles/uso terapéutico , Bencilaminas/efectos adversos , Bencilaminas/uso terapéutico , Dabigatrán , Esquema de Medicación , Embolia/etiología , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Retirada de Medicamento por Seguridad , Accidente Cerebrovascular/etiología , Warfarina/uso terapéutico , beta-Alanina/análogos & derivados , beta-Alanina/uso terapéuticoRESUMEN
For more than a decade, the only treatments available for the prevention of recurrent venous thromboembolism, were vitamin K inhibitors, or low molecular weight heparins (LMWH). Both have been very useful for this purpose; however, with the inconvenience of required frequent laboratory tests and the risk of provoking major hemorrhages. LMWH also carry the risk for immune reactions and the high cost of using it for an extended period of time. With the advent of the new anticoagulants, there is no need for laboratory tests, but there is no way to individualize the dose, or to neutralize their effect. They are also very expensive. Several recent articles have shown that aspirin, as the only treatment for the prevention of recurrent venous thromboembolism, gave good results in comparison to placebo. It has also been found that, after hip replacement surgery, the frequency of thromboembolism was similar in those patients treated with aspirin and those treated with LMWH. These results could open a new path in the search for the ideal treatment for the prevention of recurrent venous thromboembolism.