Clinical value of a tool for managing oral anticoagulation in nonvalvular atrial fibrillation in primary health care. Randomized clinical trial.

INTRODUCTION AND OBJECTIVES: The management of atrial fibrillation is complex and requires improvement at strategic points, such as in the control of patients treated with vitamin K antagonists. The aim of this study was to evaluate the impact on health outcomes of a nonvalvular atrial fibrillation decision support tool based on visualization of the time in therapeutic range in primary care. METHODS: The present randomized clinical trial was conducted in 2018 with a 1-year follow-up in 325 primary care centers in Catalonia. In the intervention centers, the decision support tool was installed to control the time in therapeutic range of patients treated with vitamin K antagonists. The tool was not visualized in the control group. This clinical trial was registered with ClinicalTrials.gov (NCT03367325). RESULTS: In total, 44 556 patients were studied. The intervention protected against admission for stroke (adjusted odds ratio [OR], 0.70; 95% confidence interval [95%CI], 0.55-0.88). The number needed to treat was 3502 (95%CI, 3305-3725) while the number of admissions for stroke avoided was 12.63 (95%CI, 11.88-13.38). The intervention also protected against mortality (adjusted OR, 0.78; 95%CI, 0.67-0.90), with a number needed to treat of 13 687 (95%CI, 10 789-18 714) and number of deaths avoided of 3.23 (95%CI, 2.36-4.10). CONCLUSIONS: The decision support tool was associated with slight reductions in the numbers of admissions for ischemic stroke and mortality. Although the follow-up time was short and the effect of the intervention was small, the results are valuable and could improve implementation of the tool.

[Direct-acting oral anticoagulants in antiphospholipid syndrome: A systematic review]. / Anticoagulantes de acción directa en el síndrome antifosfolípido. Revisión sistemática.

The objective of the systematic review is to analyze the efficacy of direct-acting oral anticoagulants (DOAC) in the prophylaxis of thrombosis in antiphospholipid syndrome (APS). We searched for clinical trials, cohort studies and meta-analyses published from January 1, 2012 to September 30, 2022. Articles that analyzed the efficacy of DOAC in the prevention of thrombosis recurrence, with or without comparison with antivitamin K (VKA) drugs, were selected. DOACs, specifically rivaroxaban and apixaban, were significantly less effective than VKAs in preventing recurrence of thrombosis in patients with APS and prior arterial thrombosis or the concomitant presence of two or three different antiphospholipid antibodies. The proportion of patients with severe bleeding as side effect are similar in those treated with DOAC and with VKA. The results argue against the use of DOAC in the treatment of patients with thrombotic APS.

Uso inadecuado del fármaco acenocumarol en la fibrilación auricular no valvular

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

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

Estudio del desempeño analítico del dispositivo portátil microINR en pacientes anticoagulados con acenocumarol / Analytical performance of the microINR portable device in acenocoumarol anticoagulated patients

Resumen La razón internacional normalizada (RIN) se utiliza para controlar a los pacientes anticoagulados con antagonistas de la vitamina K. El objetivo de este estudio fue evaluar el desempeño del nuevo dispositivo portátil microINR, que utiliza tromboplastina recombinante, en pacientes anticoagulados con acenocumarol. Grupo 1: los pacientes proporcionaron muestras de sangre venosa y capilar para realizar pruebas paralelas que permitieron comparar microINR con cinco combinaciones diferentes de reactivo/sistema de detección: tromboplastina de cerebro de conejo con detección nefelométrica, foto-óptica y por viscosidad y tromboplastina humana recombinante con detección nefelométrica y fotoóptica. Todas las tromboplastinas tenían un índice de sensibilidad internacional (ISI) específico de equipo informado por el fabricante menor de 1,10. Grupo 2: los resultados de microINR se compararon con CoaguChek como dispositivo preestablecido. La precisión se evaluó utilizando materiales de control líquidos. El coeficiente de variación del material de control en microINR fue de 6,2%. El análisis de regresión de Passing-Bablok y Bland-Altman mostró un coeficiente de correlación superior a 0,92 y un pequeño sesgo cercano a cero para todas las comparaciones de microINR con cada método tradicional realizado con sangre venosa. Ambos dispositivos portátiles tuvieron un muy buen coeficiente de correlación (r=0,98) y un pequeño sesgo de 0,02. Los resultados muestran un acuerdo clínico del 100% con un grado de concordancia Kappa mayor de 0,63 para todos los métodos tradicionales y de 0,82 para la comparación con Coagu- Chek. De acuerdo a los resultados obtenidos, el microINR es adecuado para el control de pacientes anticoagulados con acenocumarol.

Abstract The international normalised ratio (INR) is used to monitor vitamin K antagonist anticoagulated patients. The aim of this study was to evaluate the performance of the microINR portable device in acenocoumarol anticoagulated patients. Group 1: patients provided capillary and venous blood samples for parallel testing comparing microINR with five different pairs of reagent/clot detection systems: brain rabbit thromboplastin with nephelometric, photooptic and viscocity clot detection and recombinant human thromboplastin with nephelometric and photooptical detection. All thromboplastins have an instrument-specific International Sensitivity Index (ISI) lower than 1.10 reported by the manufacturer. Group 2: microINR results were compared with CoaguChek as an established device. Precision was assessed using liquid control materials. The control material coefficient of variation obtained in microINR device was 6.2%. The Passing-Bablok and Bland-Altman regression analysis showed a correlation coefficient greater than 0.92 and a small bias close to zero for all comparisons of microINR with each traditional coagulation method performed on venous blood samples. Both portable devices had a good correlation (r=0.98) and a very low bias of 0.02. The results show clinical agreement of 100% with a Kappa greater than 0.63 for different traditional INR and greater than 0.83 for CoaguChek. The performance microINR is suitable for the anticoagulation control of patients taking acenocumarol.

Resumo A razão normalizada internacional (INR) é utilizada para monitorar pacientes anticoagulados com antagonistas da vitamina K. O objetivo deste estudo foi avaliar o desempenho do dispositivo portátil microINR, um novo dispositivo que utiliza tromboplastina recombinante, em pacientes anticoagulados com acenocumarol. Grupo 1: os pacientes forneceram amostras de sangue venoso e capilar para testes paralelos que permitiram a comparação do microINR com cinco combinações diferentes de reagente/ sistema de detecção: tromboplastina de cérebro de coelho com detecção nefelométrica, foto-óptica e de viscosidade. Tromboplastina humana recombinante com detecção nefelométrica e foto-óptica. Todas as tromboplastinas tinham o Índice de Sensibilida de Internacional (ISI) específico do kit relatado pelo fabricante inferior a 1,10. Grupo 2: os resultados do microINR foram comparados com o CoaguChek como dispositivo padrão. A precisão foi avaliada usando materiais de controle líquidos. O coeficiente de variação do material de controle em microINR foi de 6,2%. A análise de regressão de Passing-Bablok e Bland-Altman mostrou um coeficiente de correlação maior que 0,92 e um pequeno viés próximo a zero para todas as variáveis. sangue. Ambos os wearables tiveram um coeficiente de correlação muito bom (r=0,98) e um pequeno viés de 0,02. Os resultados mostram 100% de concordância clínica com grau de concordância Kappa maior que 0,63 para todos os métodos tradicionais e 0,82 para a comparação com CoaguChek. De acordo com os resultados obtidos, o microINR é adequado para o controle de pacientes anticoagulados com acenocumarol.

Paciente con incumplimiento terapéutico en situación vulnerable. Intervención coordinada de una farmacia comunitaria y del equipo de atención primaria / Patient with therapeutic non-compliance in a vulnerable situation. Coordinated intervention of a community pharmacy and the primary care team

PRESENTACIÓN DEL CASO / ANTECEDENTES: mujer francesa de 81 años, afincada en Tenerife, que no habla español, Es una paciente polimedicada, tratada con Acenocumarol y Bromazepam, que en la farmacia refiere sufrir frecuentes hemorragias, así como aturdimiento y caídas frecuentes.EVALUACIÓN: la farmacéutica entrevistó a la paciente, detectando la toma de Bromazepam en el desayuno, cuando estaba prescrita en la noche, lo que podría explicar el aturdimiento y las caídas. Se detectó que la paciente no comprendía los símbolos de la pauta de acenocumarol, ni las instrucciones escritas en español por su médico. Su pauta estaba caducada y se comprobó que la paciente no asistía a los controles del índice INR. El incumplimiento en la frecuencia de dichos controles eleva el riesgo de hemorragias, según se describe en la bibliografía.INTERVENCIÓN: en visita presencial en el Centro de Salud, su médico, la farmacéutica y paciente acordaron utilizar Sistemas Personalizados de Dosificación (SPD) y prestar apoyo a la paciente para que asistiera a los controles de INR. Las pautas de acenocumarol se entregaron por parte del médico directamente a la farmacia por correo electrónico.RESULTADO / SEGUIMIENTO: en las primeras semanas se detectó una mejoría del estado general de la paciente. Sin embargo, tres semanas después apareció hemorragia digestiva, infección de orina, confusión y trastorno de conducta. Las hemorragias gastrointestinales constituyen el principal efecto adverso de los anticoagulantes, habiéndose descrito que los sangrados menores aumentan el riesgo de aparición de hemorragias mayores. (AU)

Acenocumarol: uso, adherencia y conocimiento del usuario. Oportunidades para la Atención Farmacéutica / Acenocumarol: use, adherence and knowledge. Opportunities for Pharmaceutical Care

Objetivo: El acenocumarol se mantiene como terapia anticoagulante (TAO) de primera elección. El objetivo de este estudio es valorar y mejorar el conocimiento que sobre el medicamento tienen sus usuarios y favorecer la personalización de la Atención Farmacéutica. Método: 60 pacientes usuarios de acenocumarol de 6 farmacias de Tenerife han participado en una encuesta anónima para valorar el uso, la adherencia y el conocimiento del fármaco. Resultados: 16% de los usuarios desconoce la indicación para la que se les prescribe el anticoagulante, un 32% son pacientes sin adherencia terapéutica y existe un alto grado de desconocimiento (47%) sobre cómo actuar en caso de olvido de una toma. La duplicidad de dosis es un PRM (Problema Relacionado con el Medicamento) real para el 12% de los pacientes. El 87% usa otros tratamientos junto con el acenocumarol (antihipertensivos (24%), antihipercolesterolémicos (11%), ansiolíticos/sedantes (13%) y antiulcerosos (13%)) destacando el uso conjunto de acenocumarol y analgésicos/antiinflamatorios en el 11% de nuestros usuarios de acenocumarol lo que se identifica como un riesgo potencial grave de PRM por interacción. El 35% de los pacientes desconoce las interacciones del acenocumarol, un 70% afirma haber recibido información sobre el fármaco y sólo un 42% de los pacientes manifiesta no haber leído el prospecto. Conclusiones: Se pone de manifiesto la necesidad de mejorar el conocimiento sobre este fármaco por parte del paciente. La intervención farmacéutica mediante la dispensación activa e informada y el seguimiento fármaco terapéutico personalizado permitiría la detección y prevención de PRM durante el uso de acenocumarol.(AU)

Aims: Acenocoumarol remains the first-line anticoagulant therapy (OAT). The objective of this study is to assess and improve the knowledge that users have about this drug and advance in the personalization of pharmaceutical care. Method: 60 acenocoumarol patients from 6 Tenerife pharmacies have participated in an anonymous survey to assess the use, adherence and knowledge of the drug. Results: 16% of acenocoumarol users do not know the indication for which the anticoagulant is prescribed, 32% are patients without therapeutic adherence and there is a high degree of ignorance (47%) about how to act in case of forgetting a dose. Duplication of doses is a real DRP (Drug Related Problem) for 12% of patients. 87% of those surveyed use other treatments together with acenocoumarol (antihypertensive (24%), antihypercholesterolemic (11%), anxiolytic / sedative (13%) and antiulcer (13%)), highlighting the joint use of acenocoumarol and analgesic/anti-inflammatory in 11% of our acenocoumarol users this is identified as a potential serious risk of DRP by interaction. 35% of the patients admit that they are unaware of the possible interactions of acenocoumarol, 70% of the patients affirm that they have received information about the drug, and only 42% of the patients state that they have not read the package leaflet. Conclusions: The need to improve knowledge about this drug by the patient is highlighted. Pharmaceutical intervention through active and informed dispensing and personalized therapeutic drug monitoring would allow the detection and prevention of DRP during the use of acenocoumarol.(AU)

Análisis farmacogenético retrospectivo de una paciente pediátrica en tratamiento anticoagulante: caso clínico / Retrospective pharmacogenetic analysis of a pediatric patient under anticoagulant treatment: Clinical case

Se presenta el caso clínico de una paciente de 10 años diagnosticada con miocardiopatía dilatada, quien registró valores en el índice internacional normalizado (International Normalized Ratio, INR) superiores a 10 con la dosis estándar de acenocumarol, además de otros valores que indicaban el estado incoagulable, lo que obligó a suspender y reiniciar el tratamiento en varias ocasiones. Después de más de 30 días de tratamiento, sorprendentemente se lograron los niveles esperados y estables en el INR con la mitad de la dosis recomendada para una paciente de su edad y peso.Se decidió hacer un análisis farmacogenético retrospectivo del caso mediante RT-PCR con sondas TaqMan™ que incluyó cinco polimorfismos de un solo nucleótido y distinto grado de asociación con la dosis-respuesta a los fármacos antivitamínicos K (AVK): rs2108622 (gen CYP4F2), rs9923231, rs7294 (gen VKORC1), rs1799853 y rs1057910 (gen CYP2C9). La paciente resultó ser homocigota para el rs9923231 (VKORC1) y heterocigota para el rs2108622 (CYP4F2). Se ha evidenciado a nivel nacional e internacional que este perfil genético está fuertemente asociado con una necesidad de dosis menores de antivitamínicos K.En conclusión, el análisis farmacogenético confirmó que la condición genética de la paciente, la cual conlleva una baja expresión de la enzima VKORC1 (blanco terapéutico de los antivitamínicos K), hacía predecible la necesidad de una dosis menor a la establecida según los protocolos clínicos recomendados por la Food and Drug Administration (FDA) y PharmGKB™ para los fármacos cumarínicos. El análisis genotípico previo de la paciente hubiese permitido alcanzar el rango terapéutico más prontamente, evitando potenciales riesgos de hemorragia, lo que demuestra la importancia de los análisis farmacogenéticos en tratamientos de gran variabilidad y estrecho rango terapéutico.

Abstract We present the clinical case of a 10-year-old patient diagnosed with dilated cardiomyopathy who registered INR values above 10 upon receiving standard doses of acenocoumarol, as well as other values reported as uncoagulable, forcing the discontinuation and restart of treatment more than once. Expected and stable INR levels were achieved after more than 30 days of treatment, surprisingly with half the recommended dose for a patient of her age and weight. We decided to conduct a retrospective pharmacogenomic analysis including nucleotide genetic polymorphisms (SNPs) with different degrees of association with the dose/response to antivitamin K (AVK) drugs: rs2108622 (gene CYP4F2), rs9923231, rs7294 (gene VKORC1), rs1799853, and rs1057910 (CYP2C9 gene) using TaqMan® RT-PCR. The patient was homozygous for rs9923231 (VKORC1) and heterozygous for rs2108622 (CYP4F2), a genetic profile strongly associated with a requirement of lower AVK doses as shown by national and international evidence. In conclusion, the pharmacogenetic analysis confirmed that this patient's genetic conditions, involving low expression of the VKA therapeutic target, required a lower dose than that established in clinical protocols as recommended by the Food and Drug Administration (FDA) and the PharmGKB® for coumarin drugs. A previous genotypic analysis of the patient would have allowed reaching the therapeutic range sooner, thus avoiding potential bleeding risks. This shows the importance of pharmacogenetic analyses for highly variable treatments with a narrow therapeutic range.

Calcifilaxis: factores de riesgo y hallazgos histológicos en una serie de casos de un hospital terciario / Calciphylaxis: Risk Factors and Histologic Findings in a Case Series From a Tertiary Care Referral Hospital

En los últimos años se han producido importantes avances en el conocimiento de la calcifilaxis, al haberse identificado nuevos factores de riesgo para su desarrollo, y hallazgos histológicos que podrían ser de ayuda al diagnóstico. Nuestro propósito al realizar este estudio ha sido revisar retrospectivamente los casos de calcifilaxis atendidos en nuestro hospital en los últimos 13 años, con especial atención a los aspectos más novedosos de esta patología. Se incluyó un total de 16 pacientes, 62,5% mujeres, con edad media de 67,9 años. Entre los factores asociados destacaron, aparte de la enfermedad renal avanzada (75%), los tratamientos relacionados con el metabolismo fosfocálcico (75%) y la anticoagulación (62,5%), en su mayoría con fármacos antagonistas de la vitamina K. En el estudio histológico se hallaron alteraciones en las fibras elásticas solo en un 25% de las biopsias. Once de los pacientes han fallecido, siendo la sepsis la primera causa de muerte (AU)

Recent years have seen important advances in our understanding of calciphylaxis, especially regarding newly identified risk factors and histologic findings that may aid diagnosis. This retrospective study of cases of calciphylaxis treated in our hospital in the last 13 years focuses on newly revealed aspects of this disease. We describe 16 patients (62.5% women; mean age, 67.9 years). In addition to advanced kidney disease (in 75% of our patients), other factors associated with the presence of calciphylaxis were a history of treatments related to phosphorus and calcium metabolism (75%) and anticoagulation (62.5%), usually with vitamin-K antagonists. Histology showed alterations in elastic fibers in only 25% of the biopsy specimens. Eleven of the patients died: sepsis was most often the cause (AU)

Calciphylaxis: Risk Factors and Histologic Findings in a Case Series From a Tertiary Care Referral Hospital. / Calcifilaxis: factores de riesgo y hallazgos histológicos en una serie de casos de un hospital terciario.

Recent years have seen important advances in our understanding of calciphylaxis, especially regarding newly identified risk factors and histologic findings that may aid diagnosis. This retrospective study of cases of calciphylaxis treated in our hospital in the last 13 years focuses on newly revealed aspects of this disease. We describe 16 patients (62.5% women; mean age, 67.9 years). In addition to advanced kidney disease (in 75% of our patients), other factors associated with the presence of calciphylaxis were a history of treatments related to phosphorus and calcium metabolism (75%) and anticoagulation (62.5%), usually with vitamin-K antagonists. Histology showed alterations in elastic fibers in only 25% of the biopsy specimens. Eleven of the patients died: sepsis was most often the cause.

IgA vasculitis induced by acenocoumarol. / Vasculitis IgA inducida por acenocumarol.

We present the case of a 73-year-old man with IgA vasculitis after administration of acenocoumarol, confirmed by anatomopathological study. He had cutaneous, joint and renal involvement. With the reintroduction of the drug, the clinical manifestations worsened. They were completely resolved with its suspension, without additional maintenance treatment.

After failure with acenocoumarol, rivaroxaban in antiphospholipid syndrome: A report of 2 cases. / Rivaroxabán en síndrome antifosfolipídico tras fracaso con acenocumarol: a propósito de 2 casos.

Antiphospholipid syndrome is characterized by abortions or thrombotic phenomena associated with specific antibodies. Anticoagulant therapy is based on vitamin K antagonists. We present two cases in which the use of rivaroxaban achieved control of the disease after the failure of acenocoumarol.

Rotura espontánea de bazo en paciente tratado con acenocumarol / Spontaneous rupture of spleen in a patient treated with acenocoumarol

Aunque la causa más frecuente de rotura esplénica es la traumática, podemos encontrar roturas sin relación a un traumatismo previo. Se está objetivando un aumento de roturas espontáneas en relación con tratamiento anticoagulante. Presentamos el caso de un hombre en tratamiento con acenocumarol que presentó una rotura espontánea esplénica que requirió esplenectomía urgente. La rotura de bazo es una entidad grave que debe considerarse ante todo paciente con un abdomen agudo. Aunque las causas más frecuentes de rotura esplénica atraumática son las complicaciones neoplásicas e infecciosas, se han objetivado varios casos asociados a terapias antiagregantes y anticoagulantes. Dado el aumento de población que precisa anticoagulación oral, la sobredosificación con acenocumarol debe considerarse como una posible causa de rotura esplénica. Debemos sospechar esta entidad ante todo paciente en tratamiento con anticoagulación oral con un abdomen agudo.

The splenic rupture is most commonly related to trauma, but spontaneus ruptures have also been described with increasing frequency. We present a case of a male patient with spontaneous splenic rupture due to oral anticoagulant overdose that required urgent splenectomy. The spontaneous splenic rupture is a life-threatening condition that must be considered in patients with acute abdomen. Although most ruptures are associated with to neoplastic and infectious complications , recent reports have related rupture with anticoagulant and antiaggregant therapies. Moreover, since the number of patients undergoing oral anticoagulant therapies is growing, overdose of anticoagulant drugs must be considered as a possible ethiology of spontaneous splenic rupture and suspect this association in patient with acute abdomen undergoing anticoagulant therapy.

Factors associated with poor anticoagulation control with vitaminK antagonists among outpatients attended in Internal Medicine and Neurology. The ALADIN study. / Factores asociados al mal control de la anticoagulación con antivitaminaK en pacientes con fibrilación auricular no valvular atendidos en consultas de Medicina Interna y Neurología. Estudio ALADIN.

OBJECTIVE: To identify factors associated with poor anticoagulation control with vitaminK antagonists (VKA) among outpatients with nonvalvular atrial fibrillation (NVAF) attended in Neurology and Internal Medicine in Spain. METHODS: Cross-sectional and multicenter study, from the ALADIN database, of outpatients with NVAF treated with VKA and attended in Internal Medicine and Neurology in Spain. Rates of anticoagulation control were determined with the direct and Rosendaal methods, considering data from the 6months before the inclusion. RESULTS: Out of 1,337 patients included in the ALADIN study, 750 were taking VKA, and complete information about INR values in the last 6months was available in 383 patients. Mean scores of Charlson Index, CHADS2, CHA2DS2-VASc and HAS-BLED were 1.94±1.54; 3.10±1.26; 4.63±1.54, and 2.20±0.90, respectively. 46.2% and 47.0% of patients had an adequate anticoagulation control according to the direct and Rosendaal methods, respectively. Inadequate anticoagulation control according to the direct method was associated with diabetes (OR: 2.511; 95%CI: 1.144-5.659), prior labile INR (OR: 35.371; 95%CI: 15.058-83.083) and the determination of >6INR controls in the last 6months (OR: 4.747; 95%CI: 2.094-10.759), and according to the Rosendaal method, with prior labile INR (P<.001) and HAS-BLED score (OR: 3.991; 95%CI: 2.520-6.319). CONCLUSIONS: Despite the high thromboembolic risk, only a little more than a half of patients were well controlled. Factors associated with poor anticoagulation control were diabetes, labile INR, >6INR controls and HAS-BLED.

Prognostic factors and analysis of mortality due to brain haemorrhages associated with vitamin K antagonist oral anticoagulants. Results from the TAC registry. / Factores pronósticos y análisis de la mortalidad de las hemorragias cerebrales asociadas a anticoagulantes orales antagonistas de la vitamina K. Resultados del Estudio TAC Registry.

INTRODUCTION: Intracranial haemorrhages (ICH) represent a severe and frequently lethal complication in patients treated with vitamin K antagonists (VKA). The purpose of our study is to describe the factors and clinical features associated with mortality in these patients. METHODS: We conducted an observational, retrospective, multi-centre study based on prospective stroke registries in Spain. We included all patients admitted to neurology departments during a one-year period who met the following inclusion criteria: being 18 or older, having a diagnosis of ICH, and receiving VKA. Clinical and radiological parameters and 3-month outcomes were analysed. RESULTS: A total of 235 patients from 21 hospitals were included. Mortality rate at 90 days was 42.6%. Bivariate analysis showed a significant association between death and the following factors: median NIHSS score at admission (5 [IQR = 9] vs 17 [IQR = 14] points, P<.01) and presence of an extensive hemispheric haemorrhage (4.9% vs 35%, P < .01; χ2). Extensive hemispheric haemorrhages, in addition to being the most lethal type, were associated with a shorter time to death (mean of 16.5 days; 95% CI: 7.1-26). A logistic regression model showed that only baseline NIHSS scores independently predicted death (odds ratio=1.13 [95% CI: 1.08-1.17] for each point in the scale). CONCLUSION: ICH in patients treated with VKA is associated with high mortality rates; mortality in these patients is mainly and independently associated with the clinical situation at stroke onset.

Pharmacogenetic Variation in Over 100 Genes in Patients Receiving Acenocumarol.

Coumarins are widely prescribed worldwide, and in Mexico acenocumarol is the preferred form. It is well known that despite its efficacy, coumarins show a high variability for dose requirements. We investigated the pharmacogenetic variation of 110 genes in patients receiving acenocumarol using a targeted NGS approach. We report relevant population differentiation for variants on CYP2C8, CYP2C19, CYP4F11, CYP4F2, PROS, and GGCX, VKORC1, CYP2C18, NQO1. A higher proportion of novel-to-known variants for 10 genes was identified on 41 core pharmacogenomics genes related to the PK (29), PD (3), of coumarins, and coagulation proteins (9) including, CYP1A1, CYP3A4, CYP3A5, and F8, and a low proportion of novel-to-known variants on CYP2E1, VKORC1, and SULT1A1/2. Using a Bayesian approach, we identified variants influencing acenocumarol dosing on, VKORC1 (2), SULT1A1 (1), and CYP2D8P (1) explaining 40-55% of dose variability. A collection of pharmacogenetic variation on 110 genes related to the PK/PD of coumarins is also presented. Our results offer an initial insight into the use of a targeted NGS approach in the pharmacogenomics of coumarins in Mexican Mestizos.

Conocimientos sobre el tratamiento y baja adhesión terapéutica de los pacientes anticoagulados / Knowledge about treatments and low adherence to therapy of anticoagulated patients

The main objective of this study is to measure health literacy in patients treated with oral anticoagulants and their knowledge about their treatment, and to analyze the relationships between health literacy, knowledge of their treatment, adherence, the occurrence of adverse drug reactions and several demographic and socioeconomic factors. The studied population consisted of patients going to a pharmacy with a medical prescription for oral anticoagulants. We used the abbreviated questionnaire of the European Project of Health Literacy HLS-EU-Q16 to measure health literacy and structured interviews in order to measure general knowledge about the treatment. From 133 patients in treatment with anticoagulants, 49.6% were male and the mean age was 69.72 ± 12.66 years. The levels of health literacy were in accordance with those reported by recent literature, with 51.1% of the sample having an adequate level of health literacy, 33.8% a problematic level and 15% an insufficient level. One in two patients had limited health literacy. Health literacy levels and patient knowledge were poor, and there was a relationship between them. Both decrease with age and increase with formal educational level and perceived socioeconomic status. We found no relationship between self-reported compliance or self-reported complications and health literacy or knowledge. Strategies should be implemented to promote empowerment, especially in chronic patients and those populations with fewer competencies in health information management

El objetivo principal de este trabajo es medir la alfabetización en salud en pacientes anticoagulados y sus conocimientos sobre el tratamiento que están utilizando, y analizar su relación con la adhesión, la aparición de complicaciones derivadas del medicamento y distintos factores sociodemográficos. La población en estudio consistió en pacientes que acuden a la Oficina de Farmacia con prescripción de anticoagulantes orales. Empleamos el cuestionario abreviado del Proyecto Europeo de Alfabetización en Salud HLS-EU-Q16 y realizamos entrevistas para medir los conocimientos sobre el tratamiento. De los 133 pacientes en tratamiento, 49.6% eran hombres y la media de edad era 69.72 ± 12.66 años. Los niveles de alfabetización en salud están en consonancia con los informados en la literatura reciente, de forma que el 51.1% presentaba un nivel de alfabetización en salud suficiente; el 33.8%, problemática, y el 15%, insuficiente. Uno de cada dos pacientes tenía un nivel limitado de alfabetización en salud. Los niveles de alfabetización en salud y el conocimiento de los pacientes son bajos, están relacionados entre sí y disminuyen con la edad, aumentan con el nivel educativo y socioeconómico. No encontramos elación entre la adhesión terapéutica y la aparición de complicaciones con alfabetización en salud o el conocimiento. Es necesario implementar estrategias para favorecer el empoderamiento, especialmente en los enfermos crónicos y los colectivos que presentan menos competencias a la hora de desenvolverse en el manejo de la información en salud

Safety of transradial diagnostic cardiac catheterization in patients under oral anticoagulant therapy.

BACKGROUND: Cardiac catheterization in anticoagulated patients is usually performed after the anticoagulation has been withdrawn, at least in the previous 48h, and sometimes bridging therapy with heparin is used. METHODS: A prospective observational study including 489 patients undergoing transradial catheterization was conducted. A total of 140 patients were under acenocoumarol (group A) and they were compared with the remainder (group B) for complications after the procedure (bleeding and vascular access complications). RESULTS: Patients in group A were older (74±12 years vs. 68±17 years, p<0.01) and the main indication for anticoagulation was atrial fibrillation (58.6%). No complications occurred during the procedures. There were no acute bleedings just after the bandage removal. During the first 24h, only 3 (2.1%) radial occlusions in group A and 2 (0.6%) in group B (p=0.14) were recorded. Hematomas between 5 and 10cm appeared in 5% of the group A vs. 4.6% in group B. During the 1-month follow-up period, one more radial occlusion in each group was recorded and there were 4 (1.1%) additional mild hematomas in group B and none in group A (p=0.48). CONCLUSIONS: Performing a transradial diagnostic cardiac catheterization without removal of the oral chronic anticoagulation appears safe in patients under acenocumarol therapy.

Emergency Surgery in a Critically Ill Patient with Major Drug-Induced Bleeding and Severe Ischaemic Heart Failure.

INTRODUCTION: Anticoagulant overdose frequently occurs in elderly populations especially in remote areas where medical services are scarce. When emergency surgery is required, such patients offer major anaesthetic challenges. CASE PRESENTATION: We describe the case of an elderly patient admitted to a surgical ward with acute abdominal pain, on dual anti-platelet therapy and acenocoumarol for a recent acute myocardial infarction treated percutaneously with two drug-eluting stents. Laboratory tests showed severe anticoagulant overdose with uncoagulable INR. The decision was made to use of both light transmission aggregometry [LTA] for platelet function testing and thromboelastography to aid in the management of perioperative haemostasis in order to prevent both severe bleeding and stent thrombosis. Surgery revealed haemoperitoneum, volvulus of the ileum and a venous mesenteric infarction. Intraoperative blood loss was minimal and no blood products were administered. Postoperative course was uneventful without either thrombotic or haemorrhagic complications and the patient was discharged from the Postanaesthesia Care Unit on postoperative day two. CONCLUSION: The use of aggregometry and thrombography helped in both evaluation and management of haemostasis of a high-risk patient by goal-directed administration of pro-and anti-coagulants.

[Level of control and treatment adherence of anticoagulation with acenocoumarol in Primary Care]. / Grado de control y cumplimiento terapéutico de la anticoagulación con acenocumarol en Atención Primaria.

OBJECTIVES: To determine the level of control in treatment compliance in a sample of patients who were treated with acenocoumarol attended in Primary Care settings. MATERIAL AND METHODS: Cross-sectional study. Patients with non-valvular atrial fibrillation treated with acenocoumarol were included. The sample size was calculated based on previous studies. Data of patients who possessed International Normalized Ratio (INR) values in last 6 months in medical consult were collected. It was considered that the INR control was inadequate when the percentage of INR values within the therapeutic range was less than 60% in the last 6 months. Assessment of compliance by telephone interview was conducted by the Morisky-Green Test. RESULTS: One hundred and ninety-one patients, 110 women (57.6%) with an average age of 76.5±9.4 years were included. Seventy-six patients (39.8%) were in therapeutic range (INR: 2-3) and 115 patients (60.2%) were out of range (below 2 the 20.9% and above 3 the 39.3%). Poor control of INR increased to the age of 85 years (<75 years: 57.8%; 75-85 years: 67.6%;>85 years: 61.5%). Ninety patients responded to the compliance questionnaire (78.3%), being compliant 74 (82.2%) and non-compliant 16 (17.8%). CONCLUSIONS: Six of 10 patients undergoing treatment with acenocoumarol are out of range and nearly 2 of each 10 patients out of range does not accomplish the treatment. We call attention to the need to make a systematically review of adherence in anticoagulated patients attended in Primary Care settings.