The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation.

The current manuscript is the second update of the original Practical Guide, published in 2013 [Heidbuchel et al. European Heart Rhythm Association Practical Guide on the use of new oral anticoagulants in patients with non-valvular atrial fibrillation. Europace 2013;15:625-651; Heidbuchel et al. Updated European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist anticoagulants in patients with non-valvular atrial fibrillation. Europace 2015;17:1467-1507]. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF) and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to coordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are as follows i.e., (1) Eligibility for NOACs; (2) Practical start-up and follow-up scheme for patients on NOACs; (3) Ensuring adherence to prescribed oral anticoagulant intake; (4) Switching between anticoagulant regimens; (5) Pharmacokinetics and drug-drug interactions of NOACs; (6) NOACs in patients with chronic kidney or advanced liver disease; (7) How to measure the anticoagulant effect of NOACs; (8) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (9) How to deal with dosing errors; (10) What to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (11) Management of bleeding under NOAC therapy; (12) Patients undergoing a planned invasive procedure, surgery or ablation; (13) Patients requiring an urgent surgical intervention; (14) Patients with AF and coronary artery disease; (15) Avoiding confusion with NOAC dosing across indications; (16) Cardioversion in a NOAC-treated patient; (17) AF patients presenting with acute stroke while on NOACs; (18) NOACs in special situations; (19) Anticoagulation in AF patients with a malignancy; and (20) Optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA website (www.NOACforAF.eu).

Circulating small-sized endothelial microparticles as predictors of clinical outcome after chemotherapy for breast cancer: an exploratory analysis.

PURPOSE: Therapeutic exploitation of angiogenesis in breast cancer has been limited by the lack of reliable biomarkers. Circulating small-sized endothelial microparticles (sEMP) are likely to play a significant role as messengers of angiogenesis. Higher levels of EMP have been observed in cancer patients, but their prognostic value in breast cancer is unknown. Our aim was to determine the value of circulating sEMP as a marker of response to chemotherapy in breast cancer. METHODS: We included patients with breast cancer treated with neoadjuvant or first-line chemotherapy. Baseline and post-treatment circulating sEMP (CD144+) were quantified using a flow cytometer approach specifically designed for analysis of small-sized particles (0.1-0.5 µm). Small-sized EMP response was defined as a post-treatment decrease of sEMP larger than the median decrease of sEMP after chemotherapy. Baseline and post-chemotherapy VEGFA levels were determined with ELISA. RESULTS: Forty-four breast cancer patients were included (19 with metastatic and 25 with locally advanced disease). Median levels of sEMP decreased after chemotherapy (P = 0.005). Response to chemotherapy showed a non-significant trend to associate with sEMP response (P = 0.056). A sEMP response was observed in 51% of patients and was associated with better overall survival (HR 0.18; 95% CI 0.04-0.87; P = 0.02) and progression free survival (HR 0.30; 95% CI 0.09-0.99; P = 0.04) in the group of women with metastatic disease. Post-chemotherapy decrease of VEGFA levels was not associated with breast cancer prognosis. CONCLUSIONS: Our results did not support sEMP as a marker of response to chemotherapy. However, our exploratory analysis suggests that in patients with metastatic breast cancer, the decrease of sEMP levels after chemotherapy is associated with better overall and disease free survival and might be superior to VEGFA levels as an angiogenesis-related prognostic marker.

The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: executive summary.

The current manuscript is the Executive Summary of the second update to the original Practical Guide, published in 2013. Non-vitamin K antagonist oral anticoagulants (NOACs) are an alternative for vitamin K antagonists (VKAs) to prevent stroke in patients with atrial fibrillation (AF), and have emerged as the preferred choice, particularly in patients newly started on anticoagulation. Both physicians and patients are becoming more accustomed to the use of these drugs in clinical practice. However, many unresolved questions on how to optimally use these agents in specific clinical situations remain. The European Heart Rhythm Association (EHRA) set out to co-ordinate a unified way of informing physicians on the use of the different NOACs. A writing group identified 20 topics of concrete clinical scenarios for which practical answers were formulated, based on available evidence. The 20 topics are (i) eligibility for NOACs; (ii) practical start-up and follow-up scheme for patients on NOACs; (iii) ensuring adherence to prescribed oral anticoagulant intake; (iv) switching between anticoagulant regimens; (v) pharmacokinetics and drug-drug interactions of NOACs; (vi) NOACs in patients with chronic kidney or advanced liver disease; (vii) how to measure the anticoagulant effect of NOACs; (viii) NOAC plasma level measurement: rare indications, precautions, and potential pitfalls; (ix) how to deal with dosing errors; (x) what to do if there is a (suspected) overdose without bleeding, or a clotting test is indicating a potential risk of bleeding; (xi) management of bleeding under NOAC therapy; (xii) patients undergoing a planned invasive procedure, surgery or ablation; (xiii) patients requiring an urgent surgical intervention; (xiv) patients with AF and coronary artery disease; (xv) avoiding confusion with NOAC dosing across indications; (xvi) cardioversion in a NOAC-treated patient; (xvii) AF patients presenting with acute stroke while on NOACs; (xviii) NOACs in special situations; (xix) anticoagulation in AF patients with a malignancy; and (xx) optimizing dose adjustments of VKA. Additional information and downloads of the text and anticoagulation cards in different languages can be found on an EHRA web site (www.NOACforAF.eu).

Management of antithrombotic drugs in association with endoscopic procedures.

The use of antithrombotic drugs (anticoagulants and antiplatelets) has increased significantly with our understanding of cardiovascular risk. Encountering patients on these therapies who require an endoscopic procedure is therefore increasingly common. At decision making the endoscopist must rely on other specialists (basically cardiologists and hematologists) as risk not only lies among increased bleeding odds but also in the possibility of thrombosis following dose discontinuation or change. Understanding the pharmacology, indications, and risks of endoscopic procedures is therefore essential if sound decisions are to be made. The efforts of four scientific societies have been brought together to provide clinical answers on the use of antiplatelets and anticoagulants, as well as action algorithms and a practical protocol proposal for endoscopy units.

[The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: executive summary]. / The 2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation: executive summary.

Ponizszy tekst jest streszczeniem drugiej aktualizacji oryginalnego praktycznego przewodnika opublikowanego w 2013 roku. Leki przeciwkrzepliwe niebedace antagonistami witaminy K (NOAC) stanowia cenna alternatywe dla antagonistów witaminy K (VKA) w zapobieganiu udarom u pacjentów z migotaniem przedsionków (AF) i uznano je za leki preferowane, szczególnie dla osób rozpoczynajacych leczenie przeciwkrzepliwe. Zarówno lekarze, jak i pacjenci przyzwyczajaja sie do ich stosowania w praktyce klinicznej, istnieje jednak wiele nierozwiazanych kwestii dotyczacych optymalnego stosowania tych leków w okreslonych sytuacjach klinicznych. Europejskie Stowarzyszenie Zaburzen Rytmu Serca (EHRA, European Heart Rhythm Association) podjelo sie koordynacji opracowania jednolitego sposobu komunikowania sie z lekarzami na temat stosowania róznych preparatów NOAC. Grupa okreslila 20 tematów zawierajacych konkretne scenariusze kliniczne, w odniesieniu do których sformulowano praktyczne wskazówki na podstawie dostepnych dowodów. Do problemów klinicznych naleza: 1) odpowiednia kwalifikacja pacjentów do leczenia; 2) praktyczne schematy rozpoczynania oraz monitorowania terapii za pomoca NOAC; 3) zagwarantowanie przestrzegania zalecen przyjmowania doustnych leków przeciwkrzepliwych; 4) zmiana schematów leczenia przeciwkrzepliwego; 5) farmakokinetyka oraz interakcje lekowe; 6) stosowanie NOAC u osób z przewlekla choroba nerek i zaawansowana choroba watroby; 7) sposoby pomiaru efektu przeciwkrzepliwego NOAC; 8) pomiar stezenia NOAC w surowicy: rzadkie wskazania, srodki ostroznosci, potencjalne "pulapki"; 9) postepowanie w przypadku pomylki w dawkowaniu; 10) postepowanie w przypadku (podejrzenia) przedawkowania bez krwawienia lub badania krzepniecia wskazujace na potencjalne ryzyko krwawienia; 11) postepowanie w przypadku krwawienia w trakcie terapii za pomoca NOAC; 12) postepowanie u pacjentów poddanych planowym zabiegom chirurgicznym, procedurom inwazyjnym czy ablacji; 13) postepowanie u pacjentów wymagajacych pilnej interwencji chirurgicznej; 14) pacjenci z AF oraz choroba wiencowa; 15) unikanie pomylek w dawkowaniu NOAC w róznych wskazaniach; 16) kardiowersja u pacjenta leczonego NOAC; 17) AF u pacjentów z ostrym udarem mózgu leczonych NOAC; 18) NOAC w sytuacjach szczególnych; 19) leczenie przeciwkrzepliwe w przypadku AF u pacjentów z nowotworami zlosliwymi; 20) optymalizacja leczenia za pomoca VKA. Dodatkowe informacje oraz materialy do pobrania, jak równiez karty leczenia przeciwkrzepliwego w kilku jezykach mozna znalezc na stronie internetowej EHRA (www.NOACforAF.eu).

[Pharmacodynamic and pharmacokinetic characteristics. Mechanism of action of the new oral anticoagulants]. / Características farmacodinámicas y farmacocinéticas. Mecanismo de acción de los nuevos anticoagulantes orales.

Thromboembolic disease, both arterial and venous, is a major cause of morbidity and mortality in developed countries. The new anticoagulants exert their action by selective, direct and reversible inhibition of a single coagulation factor. Although the results of several phase III trials have demonstrated the safety and efficacy of these drugs, their mechanism of action, as well as the pharmacodynamics and pharmacokinetics of these drugs, need to be understood for their correct use. The present review discusses the features of the new anticoagulants whose clinical development is more advanced, both those designed to block active factor X, such as rivaroxaban or apixaban, and those designed to block thrombin (also active factor II): dabigatran.

Manejo de los fármacos antitrombóticos asociados a los procedimientos endoscópicos / No disponible

Los fármacos antitrombóticos (anticoagulantes y antiagregantes) han experimentado un importante incremento de su uso derivado de los conocimientos sobre el riesgo cardiovascular. Por ello, es cada vez más frecuente encontrarnos con pacientes con estos tratamientos a los que hay que realizar procedimientos endoscópicos. En el acto de la toma de decisiones el endoscopista debe apoyarse en otros especialistas (básicamente cardiólogos y hematólogos) pues el riesgo no sólo se encuentra en las posibilidades aumentadas de sangrado, sino también en la posibilidad de trombosis ante la suspensión o variación de las dosis de dichos fármacos. Por ello es esencial conocer su farmacología, sus indicaciones y el riesgo de los procedimientos endoscópicos para poder tomar decisiones correctas. Se han aunado los esfuerzos de cuatro sociedades científicas para aportar respuestas clínicas con respecto al uso de antiagregantes y anticoagulantes, elaborando algoritmos de actuación, así como una propuesta práctica de un protocolo para las unidades de endoscopia (AU)

No disponible

Características farmacodinámicas y farmacocinéticas. Mecanismo de acción de los nuevos anticoagulantes orales / Pharmacodynamic and pharmacokinetic characteristics. Mechanism of action of the new oral anticoagulants

La enfermedad tromboembólica, tanto arterial como venosa, constituye una de las principales causas de morbimortalidad en el mundo occidental. Los nuevos anticoagulantes tienen un efecto selectivo en un único factor de la coagulación, actuando de forma directa y reversible. Al margen de los resultados de diversos ensayos en fase III que han demostrado la seguridad y eficacia de estos fármacos, es importante conocer el mecanismo de acción, así como la farmacodinamia y farmacocinética para un correcto uso. A lo largo de esta revisión, repasaremos dichos aspectos de los nuevos anticoagulantes cuyo desarrollo está más avanzado, tanto los destinados a bloquear el factor X activo: rivaroxaban, apixaban, como la trombina (o factor II activo): dabigatran (AU)

Thromboembolic disease, both arterial and venous, is a major cause of morbidity and mortality in developed countries. The new anticoagulants exert their action by selective, direct and reversible inhibition of a single coagulation factor. Although the results of several phase III trials have demonstrated the safety and efficacy of these drugs, their mechanism of action, as well as the pharmacodynamics and pharmacokinetics of these drugs, need to be understood for their correct use. The present review discusses the features of the new anticoagulants whose clinical development is more advanced, both those designed to block active factor X, such as rivaroxaban or apixaban, and those designed to block thrombin (also active factor II): dabigatran (AU)

Marcadores de hipercoagulabilidad y daño endotelial en pacientes con disfunción sistólica de origen isquémico / Thrombogenic and Endothelial Damage Markers in Patients with Ischemic Systolic Impairment

Introducción. En raras ocasiones se indica el tratamiento anticoagulante en pacientes con disfunción sistólica de origen isquémico, en ritmo sinusal. Sin embargo, teóricamente podrían estar presentes los 3 brazos que inician el proceso trombótico (tríada de Virchow): estasis sanguínea, lesión del endotelio y marcadores protrombóticos. El objetivo de nuestro estudio ha sido analizar estos dos últimos brazos. Pacientes y método. Estudiamos a 82 pacientes con cardiopatía isquémica demostrada, en ritmo sinusal, y se compararon con 32 sujetos controles de similar edad y sexo. El estudio se realizó al menos 3 meses después de un acontecimiento coronario agudo o descompensación hemodinámica. Determinamos la concentración plasmática de factor von Willebrand como marcador de daño endotelial, y de dímero D y fibrinógeno como marcadores protrombóticos. Mediante ecocardiografía definimos como disfunción sistólica una fracción de acortamiento inferior al 29 por ciento. Resultados. Los pacientes con cardiopatía isquémica demostraron valores estadísticamente superiores de factor von Willebrand (109,2 ñ 31,9 por ciento frente a 85,5 ñ 32,6 por ciento; p < 0,01), no así de dímero D ni fibrinógeno. De los 82 pacientes estudiados, 26 cumplieron criterios de disfunción sistólica. Los pacientes con disfunción sistólica tuvieron valores más elevados de dímero D (0,36 ñ 0,22 frente a 0,26 ñ 0,10 µg/ml, p = 0,04) y fibrinógeno (386 ñ 118 frente a 322 ñ 102 mg/dl, p = 0,03), sin diferencias con los valores de factor von Willebrand. Conclusiones. Los pacientes con cardiopatía isquémica, una vez transcurrido el acontecimiento agudo, presentan datos de daño endotelial, pero no de hipercoagulabilidad. Sin embargo, aquellos con disfunción sistólica presentan un estado hipercoagulable (AU)