Causas y predictores de muerte de los pacientes con fibrilación auricular que inician tratamiento con anticoagulantes orales directos / Causes and predictors of death in atrial fibrillation patients initiating treatment with direct oral anticoagulants

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Puntuación SAMe-TT 2R2: ¿es útil en todos los pacientes con fibrilación auricular no valvular? Respuesta / SAMe-TT 2R2 score: Useful in all patients with nonvalvular atrial fibrillation? Response

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La puntuación SAMe-TT2R2 no predice el tiempo en rango terapéutico tras un ingreso por insuficiencia cardiaca aguda en pacientes con fibrilación auricular / SAMe-TT2R2 score does not predict time in therapeutic range in atrial fibrillation patients after hospitalization for acute decompensated heart failure

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Repercusiones en la posología de los anticoagulantes orales no antagonistas de la vitamina K por las variaciones de la función renal de los pacientes con fibrilación auricular e insuficiencia cardiaca aguda reciente / Impact of variations in kidney function on nonvitamin k oral anticoagulant dosing in patients with atrial fibrillation and recent acute heart failure

Introducción y objetivos: El deterioro de la función renal y las fluctuaciones de esta son frecuentes en los pacientes recientemente hospitalizados por insuficiencia cardiaca aguda que presentan fibrilación auricular. El objetivo de este estudio es evaluar la necesidad hipotética de ajustes de dosis (según las fluctuaciones de la función renal) de dabigatrán, rivaroxabán y apixabán durante los 6 meses siguientes al alta hospitalaria a los pacientes con fibrilación auricular e insuficiencia cardiaca concomitantes. Métodos: Se llevó a cabo un estudio observacional en 162 pacientes con fibrilación auricular no valvular después de una hospitalización por insuficiencia cardiaca aguda descompensada a los que se practicaron determinaciones de creatinina durante el seguimiento. Se determinaron las posologías hipotéticas recomendadas de dabigatrán, rivaroxabán y apixabán según la función renal al alta. Se identificaron las variaciones aparecidas en la creatinina sérica y el aclaramiento de creatinina y los consiguientes cambios en las dosis recomendadas de estos fármacos durante 6 meses de seguimiento. Resultados: De la población total del estudio, el 44% de los pacientes habría necesitado un ajuste de la posología de dabigatrán durante el seguimiento; el 35%, la de rivaroxabán y el 29%, la de apixabán. Hubo mayor proporción de pacientes con aclaramiento de creatinina < 60 ml/min o de edad avanzada (≥ 75 años) que habrían necesitado ajuste de la dosis durante el seguimiento. Conclusiones: La necesidad de un ajuste de la posología de los anticoagulantes orales no antagonistas de la vitamina K durante el seguimiento es frecuente en los pacientes con fibrilación auricular después de una insuficiencia cardiaca aguda descompensada, sobre todo los de mayor edad y con deterioro de la función renal. Se necesitan nuevos estudios para esclarecer la importancia clínica de estas necesidades de ajuste de la dosis de los fármacos y la pauta idónea de seguimiento de la función renal de los pacientes con insuficiencia cardiaca y otros subgrupos de pacientes con fibrilación auricular (AU)

Introduction and objectives: Renal impairment and fluctuations in renal function are common in patients recently hospitalized for acute heart failure and in those with atrial fibrillation. The aim of the present study was to evaluate the hypothetical need for dosage adjustment (based on fluctuations in kidney function) of dabigatran, rivaroxaban and apixaban during the first 6 months after hospital discharge in patients with concomitant atrial fibrillation and heart failure. Methods: An observational study was conducted in 162 patients with nonvalvular atrial fibrillation after hospitalization for acute decompensated heart failure who underwent creatinine determinations during follow-up. The hypothetical recommended dosage of dabigatran, rivaroxaban and apixaban according to renal function was determined at discharge. Variations in serum creatinine and creatinine clearance and consequent changes in the recommended dosage of these drugs were identified during 6 months of follow-up. Results: Among the overall study population, 44% of patients would have needed dabigatran dosage adjustment during follow-up, 35% would have needed rivaroxaban adjustment, and 29% would have needed apixaban dosage adjustment. A higher proportion of patients with creatinine clearance < 60 mL/min or with advanced age (≥ 75 years) would have needed dosage adjustment during follow-up. Conclusions: The need for dosage adjustment of nonvitamin K oral anticoagulants during follow-up is frequent in patients with atrial fibrillation after acute decompensated heart failure, especially among older patients and those with renal impairment. Further studies are needed to clarify the clinical importance of these needs for drug dosing adjustment and the ideal renal function monitoring regime in heart failure and other subgroups of patients with atrial fibrillation (AU)

Impact of Variations in Kidney Function on Nonvitamin K Oral Anticoagulant Dosing in Patients With Atrial Fibrillation and Recent Acute Heart Failure.

INTRODUCTION AND OBJECTIVES: Renal impairment and fluctuations in renal function are common in patients recently hospitalized for acute heart failure and in those with atrial fibrillation. The aim of the present study was to evaluate the hypothetical need for dosage adjustment (based on fluctuations in kidney function) of dabigatran, rivaroxaban and apixaban during the first 6 months after hospital discharge in patients with concomitant atrial fibrillation and heart failure. METHODS: An observational study was conducted in 162 patients with nonvalvular atrial fibrillation after hospitalization for acute decompensated heart failure who underwent creatinine determinations during follow-up. The hypothetical recommended dosage of dabigatran, rivaroxaban and apixaban according to renal function was determined at discharge. Variations in serum creatinine and creatinine clearance and consequent changes in the recommended dosage of these drugs were identified during 6 months of follow-up. RESULTS: Among the overall study population, 44% of patients would have needed dabigatran dosage adjustment during follow-up, 35% would have needed rivaroxaban adjustment, and 29% would have needed apixaban dosage adjustment. A higher proportion of patients with creatinine clearance < 60 mL/min or with advanced age (≥ 75 years) would have needed dosage adjustment during follow-up. CONCLUSIONS: The need for dosage adjustment of nonvitamin K oral anticoagulants during follow-up is frequent in patients with atrial fibrillation after acute decompensated heart failure, especially among older patients and those with renal impairment. Further studies are needed to clarify the clinical importance of these needs for drug dosing adjustment and the ideal renal function monitoring regime in heart failure and other subgroups of patients with atrial fibrillation.

Comparación de las ecuaciones de filtrado glomerular estimado para determinar la posología de los nuevos anticoagulantes orales para pacientes con fibrilación auricular / Comparison of estimated glomerular filtration rate equations for dosing new oral anticoagulants in patients with atrial fibrillation

Introducción y objetivos: Los nuevos anticoagulantes orales requieren ajuste de la posología según la función renal. El objetivo de este estudio es determinar la discrepancia existente entre la hipotética posología recomendada de estos fármacos empleando diferentes ecuaciones de filtrado glomerular estimado en pacientes con fibrilación auricular. Métodos: Análisis transversal de 910 pacientes con fibrilación auricular e indicación de anticoagulación oral. Se estimó el filtrado glomerular con las ecuaciones de Cockcroft-Gault, Modification of Diet in Renal Disease y Chronic Kidney Disease Epidemiology Collaboration. Para dabigatrán, rivaroxabán y apixabán, se identificaron discrepancias de la dosis cuando no coincidían con las dosis recomendadas según se usara una u otra ecuación. Resultados: En el conjunto de la población, respecto a la ecuación de Cockcroft-Gault, la discrepancia de la posología de dabigatrán fue del 11,4% con la ecuación Modification of Diet in Renal Disease y del 10 con la Chronic Kidney Disease Epidemiology Collaboration; las discrepancias de la posología de rivaroxabán fueron del 10% y el 8,5% respectivamente. La menor discrepancia se observó con apixabán: el 1,4% con la primera y el 1,5% con la segunda. En los pacientes con un valor según la ecuación de Cockcroft-Gault < 60 ml/min o en los pacientes ancianos, las discrepancias en las posologías de dabigatrán y rivaroxabán fueron superiores, entre el 13,2 y el 30,4%. La discrepancia en cuanto a la posología de apixabán se mantuvo en un valor < 5% en estos pacientes. Conclusiones: La discrepancia en las posologías de los nuevos anticoagulantes orales empleando ecuaciones distintas es frecuente, sobre todo en los pacientes ancianos con deterioro de la función renal. Esta discrepancia fue mayor para las posologías de dabigatrán y rivaroxabán que para la de apixabán. Se necesitan nuevos estudios para esclarecer la importancia clínica de estas discrepancias y determinar la posología óptima de los anticoagulantes según la ecuación que se use para estimar la función renal (AU)

Introduction and objectives: New oral anticoagulants require dosing adjustment according to renal function. We aimed to determine discordance in hypothetical recommended dosing of these drugs using different estimated glomerular filtration rate equations in patients with atrial fibrillation. Methods: Cross-sectional analysis of 910 patients with atrial fibrillation and an indication for oral anticoagulation. The glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations. For dabigatran, rivaroxaban, and apixaban we identified dose discordance when there was disagreement in the recommended dose based on different equations. One-hundred samples from 54 patients with virologic breakthrough during entecavir, lamivudine or adefovir treatment and 21 samples from 21 nucleoside-naïve patients were tested by direct sequencing and an updated line probe assay (Innogenetics, HBV DR v.3) which incorporates probes that can detect mutations at 11 positions of the reverse transcriptase region of the HBV polymerase gene. Results: Among the overall population, relative to Cockcroft-Gault, discordance in dabigatran dosage was 11.4% for Modification of Diet in Renal Disease and 10% for Chronic Kidney Disease Epidemiology Collaboration, discordance in rivaroxaban dosage was 10% for Modification of Diet in Renal Disease and 8.5% for the Chronic Kidney Disease Epidemiology Collaboration. The lowest discordance was observed for apixaban: 1.4% for Modification of Diet in Renal Disease and 1.5% for the Chronic Kidney Disease Epidemiology Collaboration. In patients with Cockcroft-Gault < 60 mL/min or elderly patients, discordances in dabigatran and rivaroxaban dosages were higher, ranging from 13.2% to 30.4%. Discordance in apixaban dosage remained < 5% in these patients. Conclusions: Discordance in new oral anticoagulation dosages using different equations is frequent, especially among elderly patients with renal impairment. This discordance was higher in dabigatran and rivaroxaban dosages than in apixaban dosages. Further studies are needed to clarify the clinical importance of these discordances and the optimal anticoagulant dosages depending on the use of different equations to estimate renal function (AU)

Comparison of estimated glomerular filtration rate equations for dosing new oral anticoagulants in patients with atrial fibrillation.

INTRODUCTION AND OBJECTIVES: New oral anticoagulants require dosing adjustment according to renal function. We aimed to determine discordance in hypothetical recommended dosing of these drugs using different estimated glomerular filtration rate equations in patients with atrial fibrillation. METHODS: Cross-sectional analysis of 910 patients with atrial fibrillation and an indication for oral anticoagulation. The glomerular filtration rate was estimated using the Cockcroft-Gault, Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations. For dabigatran, rivaroxaban, and apixaban we identified dose discordance when there was disagreement in the recommended dose based on different equations. RESULTS: Among the overall population, relative to Cockcroft-Gault, discordance in dabigatran dosage was 11.4% for Modification of Diet in Renal Disease and 10% for Chronic Kidney Disease Epidemiology Collaboration, discordance in rivaroxaban dosage was 10% for Modification of Diet in Renal Disease and 8.5% for the Chronic Kidney Disease Epidemiology Collaboration. The lowest discordance was observed for apixaban: 1.4% for Modification of Diet in Renal Disease and 1.5% for the Chronic Kidney Disease Epidemiology Collaboration. In patients with Cockcroft-Gault<60mL/min or elderly patients, discordances in dabigatran and rivaroxaban dosages were higher, ranging from 13.2% to 30.4%. Discordance in apixaban dosage remained<5% in these patients. CONCLUSIONS: Discordance in new oral anticoagulation dosages using different equations is frequent, especially among elderly patients with renal impairment. This discordance was higher in dabigatran and rivaroxaban dosages than in apixaban dosages. Further studies are needed to clarify the clinical importance of these discordances and the optimal anticoagulant dosages depending on the use of different equations to estimate renal function.

TWEAK and NT-proBNP levels predict exercise capacity in hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate hypertrophy, myocyte disarray and increased interstitial fibrosis. The tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a cell surface cytokine with biological activities including stimulation of cell growth, induction of inflammatory cytokines and stimulation of apoptosis. There are controversial data about the potential role of TWEAK in different cardiovascular pathologies. NT-proBNP is an established biomarker of myocardial wall stress, associated with poor functional class in HCM. We hypothesized that effort capacity in patients with HCM could be related to serum levels of these biomarkers. MATERIALS AND METHODS: We included 40 haemodynamic stable HCM patients and 53 healthy controls with similar sex and age. We studied exercise capacity by maximal oxygen consumption in a limited treadmill exercise test. TWEAK and NT-proBNP were assayed by ELISA method and automated Elecsys® platform, respectively. We obtained 46 samples of myocardial tissues by septal myectomy in patients with HCM and evaluated myocardial fibrosis, immunoreaction with TWEAK antibody and apoptosis with TUNEL assay. RESULTS: We found raised TWEAK and NT-proBNP serum levels in patients when compared with control levels (both P < 0.001). In a multivariate analysis, TWEAK and NT-proBNP levels, as well as sex, remained independently associated with the effort capacity (all P < 0.05). We found an association between immunoreaction degree and the degree of myocardial fibrosis (P = 0.021), as well as apoptosis (P = 0.002) in the tissue samples from patients undergoing septal myectomy. CONCLUSIONS: TWEAK and NT-proBNP levels are biomarkers of disease severity independently associated with the effort capacity in patients with HCM.

Beta-trace protein and cystatin c as predictors of major bleeding in non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. We assessed the ability of both to predict major bleeding (MB) in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), compared to other renal function parameters and clinical risk scores. METHODS AND RESULTS: We included 273 patients. Blood samples were obtained within 24h of admission. The endpoint was MB. During a follow-up of 760 days (411-1,098 days), 25 patients (9.2%) had MB. Patients with MB had higher concentrations of BTP (0.98 mg/L; 0.71-1.16 mg/L vs. 0.72 mg/L, 0.60-0.91 mg/L, P=0.002), CysC (1.05 mg/L; 0.91-1.30 mg/L vs. 0.90 mg/L, 0.75-1.08 mg/L, P=0.003), higher CRUSADE score (39 ± 16 points vs. 29 ± 15 points, P=0.002) and lower estimated glomerular filtration rate (eGFR; 66 ± 27 vs. 80 ± 30 ml·min(-1)·1.73 m(-2), P=0.02) than patients without MB; there was no difference in creatinine level between the groups (P=0.14). After multivariable adjustment, both were predictors of MB, while eGFR and creatinine did not achieve statistical significance. Among subjects with eGFR >60 ml·min(-1)·1.73 m(-2), those with elevated concentrations of both biomarkers had a significantly higher risk for MB. Net reclassification indexes from the addition of BTP and CysC to CRUSADE risk score were 38% and 21% respectively, while the relative integrated discrimination indexes were 12.5% and 3.8%. CONCLUSIONS: Among NSTE-ACS patients, BTP and CysC were superior to conventional renal parameters for predicting MB, and improved clinical stratification for hemorrhagic risk.