Relative performance evaluation of four bleeding risk scores in atrial fibrillation patients. What does the new DOAC score provide?

BACKGROUND: Recently, the direct oral anticoagulant (DOAC) score was developed and better predicted major bleeding in DOAC-treated patients with atrial fibrillation (AF) than HASBLED did. Little is known on the new score's performance regarding other bleeding risk in AF. METHODS: We studied 14,672 patients diagnosed with AF between 2014 and 2018. During follow-up, we assessed the performance of DOAC score compared with the HASBLED, ORBIT and SWISS scores at predicting major bleeding in DOACs and non-DOACs users. Discrimination, calibration and decision curve analysis (DCA) were used to assess the risk scorer's performance. RESULTS: There were 1484 (10.1%) patients on DOACs, 9730 on vitamin K antagonist (VKA), and 3458 on non-oral anticoagulants. Over a median of 3.5 years of follow-up, 79 major bleedings occurred in the DOAC patients, and 486 in the VKA patients (cumulative incidences = 7.4 and 13.9 per 100 patient-years, respectively). Amongst the DOAC patients, the DOAC score discrimination was moderate (C-statistic = 0.711), but significantly higher than HASBLED (C = 0.640; p = 0.03), ORBIT (C = 0.660; p = 0.04), and SWISS scores (C = 0.637; p = 0.002). The DCA showed higher net benefit using DOAC score compared with the remaining scores. In the VKA patients, DOAC score showed the highest discrimination (c-statistic = 0.709), followed by ORBIT (C = 0.692; p = 0.07), HASBLED and SWISS (C = 0.635 and 0.624, respectively; p < 0.01). All risk scores calibrated well, although HASBLED showed relatively poor calibration. CONCLUSIONS: The new DOAC bleeding risk score is a valid and reasonable predictor of major bleeding over a median of 3.5 years of follow-up. Physicians can be reassured about the applicability of DOAC score for bleeding risk stratification in AF patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04364516.

Liver fibrosis and outcomes of atrial fibrillation: the FIB-4 index.

BACKGROUND AND AIMS: Liver diseases play an important role in the development and progression of atrial fibrillation (AF). The Fibrosis-4 (FIB-4) index is a non-invasive score recommended for detecting liver fibrosis. Since the association between liver fibrosis and outcomes of AF patients is still not well defined, we aim to analyze prognosis impact of FIB-4 index in those patients. METHODS: A retrospective population-based cohort study was performed with 12,870 unselected patients from a single health area in Spain with AF from 2014 to 2019. Cox regression models were used to estimate the association of FIB-4 index with mortality. The association with ischemic stroke (IS), major bleeding (MB), acute myocardial infarction (AMI), and heart failure (HF) was assessed by competing risk analysis. RESULTS: A total of 61.1%, 22.0%, and 16.9% were classified as low, moderate and high risk of liver fibrosis according to FIB-4 index, respectively. During a mean follow-up of 4.5 ± 1.7 years, FIB-4 index was associated with mortality (adjusted HR 1.04; 95% CI 1.01-1.06; p = 0.002), MB and HF (adjusted sHR 1.03, 95% CI 1.01-1.04; p = 0.004), but not with IS or with AMI. The association between FIB-4 and MB was only found in patients treated with vitamin K antagonists, not in patients on direct oral anticoagulants. CONCLUSIONS: The FIB-4 index, a non-invasive scoring method for evaluating liver fibrosis, is independently associated with all-cause mortality, MB and HF in patients with AF, suggesting that it may be useful as a risk assessment tool to identify adverse outcomes in patients with AF.

Predictive value of bleeding risk scores in elderly patients with atrial fibrillation and oral anticoagulation.

BACKGROUND: The predictive value of bleeding risk scores for atrial fibrillation in older patients is not as well known. The goal of this study was to evaluate the predictive value of HASBLED, ORBIT and ATRIA for major bleeding (MB) and intracranial hemorrhage (ICH) in patients ≥ 75 years with atrial fibrillation and oral anticoagulation (OAC). METHODS: A retrospective unicenter study including patients ≥ 75 years with atrial fibrillation (AF) and OAC. A total of 7613 patients ≥ 75 years with AF and OAC included between 2014 and 2018 (registry: NCT04364516). We analyzed the discriminative value of HASBLED, ATRIA and ORBIT scores for bleeding endpoints (major bleeding as primary endpoint and intracerebral hemorrhage as secondary). Cox regression was used to predict major bleeding with each scale and also for searching other variables potentially predictor of major bleeding. Model discrimination was assessed using Harrell's C-statistic. Calibration was assessed with goodness-of-fit test proposed by Gronnesby and Borgan. RESULTS: During a mean follow up of 4.0 years (IQR: 2.4-5.7 years), 729 patients developed MB (2.61 per 100 patients/year) and 243 patients developed ICH (0.85 per 100 patients/year). Three scores showed a low discrimination for major bleeding, being ORBIT the best (HASBLED C statistic = 0.557; ATRIA C statistic = 0.568; ORBIT C statistic = 0.595) and also a low discrimination for ICH (HASBLED C statistic = 0.509; ATRIA C statistic = 0.522; ORBIT C statistic = 0.526). Among the variables that are part of the scores and other baseline characteristics, after multivariable adjustment only sex (male), dementia, prior admission for bleeding, anemia and liver disease were found as a predictors of MB. CONCLUSIONS: In older patients under oral anticoagulation with atrial fibrillation, the risk scores HASBLED, ATRIA and ORBIT showed a weak discrimination for major bleeding and intracranial hemorrhage. Therefore, other better alternatives should be evaluated for this purpose.

Riesgo hemorrágico y embólico de los pacientes con fibrilación auricular y cáncer / Bleeding and embolic risk in patients with atrial fibrillation and cancer

Introducción y objetivos El impacto del cáncer en los eventos de los pacientes con fibrilación auricular (FA) no está claro. El objetivo de este estudio es evaluar cómo el cáncer influye en el riesgo de eventos embólicos y hemorrágicos de los pacientes con FA. Métodos Conformaron la población del estudio 16.056 pacientes de un área sanitaria española diagnosticados de FA entre 2014 y 2018. De ellos, 1.137 (7,1%) tenían antecedentes de cáncer. Durante una mediana de seguimiento de 4,9 años, se evaluó mediante un análisis de riesgos competitivos la relación entre el cáncer y las embolias y hemorragias. Resultados No se detectó asociación entre un mayor riesgo de eventos embólicos y cáncer en general (sHR=0,73; IC95%, 0,41-1,26). Sin embargo, el cáncer se asoció con un mayor riesgo hemorrágico, aunque solo en pacientes con cáncer activo (sHR=1,42; IC95%, 1,20-1,67) o radioterapia previa (sHR=1,40; IC95%, 1,19-1,65). Las escalas CHA2DS2-VASc y HAS-BLED mostraron un rendimiento subóptimo para predecir el riesgo, respectivamente, embólico y hemorrágico (estadístico c <0,50) de los pacientes no anticoagulados con cáncer activo. La relación entre el aumento de las hemorragias y la disminución de las embolias con anticoagulación fue similar en pacientes con y sin cáncer (5,6 frente a 7,8; p <0,001). Conclusiones El cáncer no se asoció con un mayor riesgo de eventos embólicos en pacientes con FA, solo con un mayor riesgo de hemorragia. Sin embargo, el cáncer activo empeoró la capacidad predictiva de las escalas CHA2DS2-VASc y HAS-BLED para predecir eventos en pacientes no anticoagulados (AU)

Introduction and objectives The impact of cancer on clinical outcomes in patients with atrial fibrillation (AF) is unclear. The aim of this study was to assess how cancer influences the prediction and risk of embolic and hemorrhagic events in patients with AF. Methods The study population comprised 16 056 patients from a Spanish health area diagnosed with AF between 2014 and 2018. Of these, 1137 (7.1%) had a history of cancer. During a median follow-up of 4.9 years, we assessed the relationship between cancer and bleeding and embolic events by competing risk analysis, considering death as a competing risk. Results No association was detected between an increased risk of embolic events and cancer overall (sHR, 0.73; 95%CI, 0.41-1.26), active cancer, or any subgroup of cancer. However, cancer was associated with an increased risk of bleeding, although only in patients with active cancer (sHR, 1.42; 95%CI, 1.20-1.67) or prior radiotherapy (sHR, 1.40; 95%CI, 1.19-1.65). Both the CHA2DS2-VASc and HAS-BLED scores showed suboptimal performance to predict embolic and bleeding risk (c-statistic <0.50), respectively, in nonanticoagulated patients with active cancer. The ratio between the increase in bleeding and the decrease in embolisms with anticoagulation was similar in patients with and without cancer (5.6 vs 7.8; P <.001). Conclusions Cancer was not associated with an increased risk of embolic events in AF patients, only with an increased risk of bleeding. However, active cancer worsened the ability of the CHA2DS2-VASc and HAS-BLED scores to predict embolic and bleeding events, respectively, in nonanticoagulated patients (AU)

Comparison of Stroke and Bleeding Risk Profile in Patients With Atrial Fibrillation and Chronic Kidney Disease.

Clinical decision making on anticoagulation in patients with chronic kidney disease with atrial fibrillation (AF) is challenging. The current strategies are based on small observational studies with conflicting results. This study explores the impact of glomerular filtration rate (GFR) in the embolic-hemorrhagic balance among a large cohort of patients with AF. The study cohort included 15,457 patients diagnosed with AF between January 2014 and April 2020. The risk of ischemic stroke and major bleeding was determined by competing risk regression. During a mean follow-up of 4.29 ± 1.82 years, 3,678 patients (23.80%) died, 850 (5.50%) had an ischemic stroke, and 961 (6.22%) had a major bleeding. The incidence of stroke and bleeding increased as baseline GFR decreased. Interestingly, in GFR <30 ml/min/1.73 m2, the bleeding risk was clearly higher than the embolic risk. As GFR decreased, anticoagulation was associated with an increased bleeding risk (subdistribution hazard ratio 1.700, 95% confidence interval [CI] 1.13 to 2.54, p = 0.009 for patients with GFR 30 to 59 ml/min/1.73 m2 and 2.00, 95% CI 0.77 to 5.21, p = 0.156 for subjects with <30 ml/min/1.73 m2 compared with those with GFR >60 ml/min/1.73 m2, respectively), but it was not associated with a decrease in embolic risk in patients with GFR <30 ml/min/1.73 m2 (subdistribution hazard ratio 1.91, 95% CI 0.73 to 5.04, p = 0.189) In GFR <30 ml/min/1.73 m2, the increase of major bleeding risk was higher than the increase of ischemic stroke risk, with a negative anticoagulation balance (greater increase in bleeding than reduction in embolism).

Bleeding and embolic risk in patients with atrial fibrillation and cancer.

INTRODUCTION AND OBJECTIVES: The impact of cancer on clinical outcomes in patients with atrial fibrillation (AF) is unclear. The aim of this study was to assess how cancer influences the prediction and risk of embolic and hemorrhagic events in patients with AF. METHODS: The study population comprised 16 056 patients from a Spanish health area diagnosed with AF between 2014 and 2018. Of these, 1137 (7.1%) had a history of cancer. During a median follow-up of 4.9 years, we assessed the relationship between cancer and bleeding and embolic events by competing risk analysis, considering death as a competing risk. RESULTS: No association was detected between an increased risk of embolic events and cancer overall (sHR, 0.73; 95%CI, 0.41-1.26), active cancer, or any subgroup of cancer. However, cancer was associated with an increased risk of bleeding, although only in patients with active cancer (sHR, 1.42; 95%CI, 1.20-1.67) or prior radiotherapy (sHR, 1.40; 95%CI, 1.19-1.65). Both the CHA2DS2-VASc and HAS-BLED scores showed suboptimal performance to predict embolic and bleeding risk (c-statistic <0.50), respectively, in nonanticoagulated patients with active cancer. The ratio between the increase in bleeding and the decrease in embolisms with anticoagulation was similar in patients with and without cancer (5.6 vs 7.8; P <.001). CONCLUSIONS: Cancer was not associated with an increased risk of embolic events in AF patients, only with an increased risk of bleeding. However, active cancer worsened the ability of the CHA2DS2-VASc and HAS-BLED scores to predict embolic and bleeding events, respectively, in nonanticoagulated patients.

Comparison of Outcomes in Patients With Atrial Fibrillation Under Oral Anticoagulation Therapy Analyzed by Body Weight (<60, 60 to 100, and >100 kg).

There is limited knowledge regarding the efficacy and safety of fixed-dose oral anticoagulants in overweight patients because of the possible increased risk of embolism and hemorrhage. This study aimed to evaluate embolic, hemorrhagic, and mortality events in anticoagulated patients, administered both antivitamin K and direct oral anticoagulants based on the body weight (<60 kg, 60 to 100 kg and >100 kg). A retrospective registry-based cohort study including all consecutive patients with a diagnosis of atrial fibrillation between January 2014 and January 2018 in the health area of Vigo (Galicia, Spain) was used (CardioCHUVI-AF registry; ClinicalTrials.gov identifier: NCT04364516). The final cohort comprised 11,821 AF patients. The cohort was classified into 3 categories: low body weight ([LBW], <60 kg, 924 patients); middle body weight (60 to 100 kg, 9,546 patients); and high body weight ([HBW], >100 kg, 958 patients). Outcomes were predicted using the Fine and Gray model and Cox proportional hazards model when appropriate. Middle body weight was the reference group. No association was found between the weight and major bleeding in the univariate analyses: LBW with a sub-distribution hazard ratio (sHR) of 1.13 (95% confidence interval [CI] 0.92 to 1.41), and HBW with an sHR of 1.02 (95% CI 0.83 to 1.26). Stroke/systemic embolism events occurred in 817 patients (6.6%). In the univariate analyses, we found an association between weight and risk of stroke/systemic embolism: LBW sHR 1.37 (95% CI 1.09 to 1.72), and HBW sHR 0.66 (95% CI 0.49 to 0.89) but no association was found in the multivariable model. The same situation was observed with all-cause death: in the univariable model, LBW presented a hazard ratio of 1.48 (95% CI 1.31 to 1.68) and the HBW group presented a hazard ratio of 0.53 (95%CI 0.44 to 0.63) whereas no significant association was found in the multivariable model. We conclude that in our registry, extreme weights were not related to more events during follow-up.

Nutrition status, obesity and outcomes in patients with atrial fibrillation.

INTRODUCTION AND OBJECTIVES: A paradoxical protective effect of obesity has been previously reported in patients with atrial fibrillation (AF). The aim of this study was to determine the impact of nutritional status and body mass index (BMI) on the prognosis of AF patients. METHODS: We conducted a retrospective population-based cohort study of patients with AF from 2014 to 2017 from a single health area in Spain. The CONUT score was used to assess nutritional status. Cox regression models were used to estimate the association of BMI and CONUT score with mortality. The association with embolism and bleeding was assessed by a competing risk analysis. RESULTS: Among 14 849 AF patients, overweight and obesity were observed in 42.6% and 46.0%, respectively, while malnutrition was observed in 34.3%. During a mean follow-up of 4.4 years, 3335 patients died, 984 patients had a stroke or systemic embolism, and 1317 had a major bleeding event. On univariate analysis, BMI was inversely associated with mortality, embolism, and bleeding; however, this association was lost after adjustment by age, sex, comorbidities, and CONUT score (HR for composite endpoint, 0.98; 95%CI, 0.95-1.01; P=.719). Neither obesity nor overweight were predictors of mortality, embolism, and bleeding events. In contrast, nutritional status-assessed by the CONUT score-was associated with mortality, embolism and bleeding after multivariate analysis (HR for composite endpoint, 1.15; 95%CI, 1.14-1.17; P<.001). CONCLUSIONS: BMI was not an independent predictor of events in patients with AF in contrast to nutritional status, which showed a strong association with mortality, embolism, and bleeding. The study was registered at ClinicalTrials.gov (Identifier: NCT04364516).

Prevalence and Prognostic Significance of Malnutrition in Patients With Acute Coronary Syndrome.

BACKGROUND: Malnutrition is associated with poor prognosis in a wide range of illnesses. However, its prognostic impact in patients with acute coronary syndrome (ACS) is not well known. OBJECTIVES: This study sought to report the prevalence, clinical associations, and prognostic consequences of malnutrition in patients with ACS. METHODS: In this study, the Controlling Nutritional Status (CONUT) score, the Nutritional Risk Index (NRI), and the Prognostic Nutritional Index (PNI) was applied to 5,062 consecutive patients with ACS. The relationships between malnutrition risk and all-cause mortality and major cardiovascular events (MACEs) (cardiovascular mortality, reinfarction, or ischemic stroke) were examined. RESULTS: According to the CONUT score, NRI, and PNI, 11.2%, 39.5%, and 8.9% patients were moderately or severely malnourished, respectively; 71.8% were at least mildly malnourished by at least 1 score. Although worse scores were most strongly related to lower body mass index, between 8.4% and 36.7% of patients with a body mass index of ≥25 kg/m2 were moderately or severely malnourished, depending on the nutritional index used. During a median follow-up of 3.6 years (interquartile range: 1.3 to 5.3 years), 830 (16.4%) patients died, and 1,048 (20.7%) had MACEs. Compared with good nutritional status, malnutrition was associated with significantly increased risk for all-cause death (adjusted hazard ratio for moderate and severe degrees of malnutrition, respectively: 2.02 [95% confidence interval (CI): 1.65 to 2.49] and 3.65 [95% CI: 2.41 to 5.51] for the CONUT score, 1.40 [95% CI: 1.17 to 1.68] and 2.87 [95% CI: 2.17 to 3.79] for the NRI, and 1.71 [95% CI: 1.37 to 2.15] and 1.95 [95% CI: 1.55 to 2.45] for the PNI score; p values <0.001 for all nutritional indexes). Similar results were found for the CONUT score and PNI regarding MACEs. All risk scores improve the predictive ability of the GRACE (Global Registry of Acute Coronary Events) risk score for both all-cause mortality and MACEs. CONCLUSIONS: Malnutrition is common among patients with ACS and is strongly associated with increased mortality and cardiovascular events. Clinical trials are needed to prospectively evaluate the efficacy of nutritional interventions on outcomes in patients with ACS.

Relación de la composición corporal medida por DEXA con el estilo de vida y la satisfacción con la imagen corporal en estudiantes universitario / Relationship of body composition measured by DEXA with lifestyle and satisfaction with body image in university students

Introducción: el índice de masa corporal (IMC) es una medida subrogada de la adiposidad corporal, por lo que puede infradiagnosticar sobrepeso y obesidad, lo que hace necesario definir variables más adecuadas para su correcto diagnóstico. Objetivo: comparar la categorización de sobrepeso y obesidad según el porcentaje de grasa medido con absorciometría de rayos X de energía dual (DEXA) con el IMC y la fórmula Clínica Universidad de Navarra - Body Adiposity Estimator (CUN-BAE), así como su relación con la adherencia a la dieta mediterránea, la actividad física y la satisfacción con la imagen corporal. Sujetos y métodos: estudio descriptivo transversal llevado a cabo en una muestra de 64 estudiantes de Medicina. Se determinaron peso, talla, perímetro de cintura, porcentaje de grasa medido con DEXA, adherencia a la dieta mediterránea, nivel de actividad física y satisfacción con la imagen corporal. Resultados: el IMC infradiagnostica sobrepeso respecto al porcentaje de grasa medido por DEXA mientras que la ecuación CUN-BAE presenta una buena correlación. El porcentaje de grasa se asocia inversamente con la satisfacción con la imagen corporal con mayor fuerza que el IMC. Conclusión: se necesitan nuevas herramientas capaces de distinguir los casos con IMC normal cuyo porcentaje de grasa corporal está elevado. Sería útil estudiar si el empleo de un cuestionario de satisfacción con la imagen corporal en personas clasificadas como normopeso podría distinguir a aquellas con una mayor probabilidad de exceso de grasa y así emplear estudios más exhaustivos en este colectivo

Introduction: body mass index (BMI) can under-diagnose overweight and obesity as it is a surrogate measure of central adiposity, making it necessary to define more adequate variables for its correct diagnosis. Objective: to compare the categorization of overweight and obesity according to the percentage of fat measured with dual-energy X-ray absorptiometry (DEXA) with the BMI and the Clínica Universidad de Navarra - Body Adiposity Estimator (CUN-BAE) formula, as well as their relationship with adherence to the Mediterranean diet, physical activity and satisfaction with body image. Subjects and methods: cross-sectional study conducted in 64 medical students. We determined weight, height, waist circumference, percentage of fat measured with DEXA, adherence to the Mediterranean diet, level of physical activity and degree of satisfaction with body image. Results: BMI underdiagnoses overweight with respect to the percentage of fat measured by DEXA while CUN-BAE has a good correlation. Percentage of fat is inversely associated with satisfaction with body image more strongly than the BMI. Conclusion: the limitations of BMI to diagnose excess body fat pose the need for new tools to distinguish patients with normal BMI whose percentage of body fat is high. It would be useful to assess whether the use of a questionnaire of satisfaction with body image in people classified as normal weight could distinguish individuals with a higher probability of excess of fat, and thus, employ more accurate study methods in this group

[Relationship of body composition measured by DEXA with lifestyle and satisfaction with body image in university students]. / Relación de la composición corporal medida por DEXA con el estilo de vida y la satisfacción con la imagen corporal en estudiantes universitarios.

INTRODUCTION: Introduction: body mass index (BMI) can under-diagnose overweight and obesity as it is a surrogate measure of central adiposity, making it necessary to define more adequate variables for its correct diagnosis. Objective: to compare the categorization of overweight and obesity according to the percentage of fat measured with dual-energy X-ray absorptiometry (DEXA) with the BMI and the Clínica Universidad de Navarra - Body Adiposity Estimator (CUN-BAE) formula, as well as their relationship with adherence to the Mediterranean diet, physical activity and satisfaction with body image. Subjects and methods: cross-sectional study conducted in 64 medical students. We determined weight, height, waist circumference, percentage of fat measured with DEXA, adherence to the Mediterranean diet, level of physical activity and degree of satisfaction with body image. Results: BMI underdiagnoses overweight with respect to the percentage of fat measured by DEXA while CUN-BAE has a good correlation. Percentage of fat is inversely associated with satisfaction with body image more strongly than the BMI. Conclusion: the limitations of BMI to diagnose excess body fat pose the need for new tools to distinguish patients with normal BMI whose percentage of body fat is high. It would be useful to assess whether the use of a questionnaire of satisfaction with body image in people classified as normal weight could distinguish individuals with a higher probability of excess of fat, and thus, employ more accurate study methods in this group.

INTRODUCCIÓN: Introducción: el índice de masa corporal (IMC) es una medida subrogada de la adiposidad corporal, por lo que puede infradiagnosticar sobrepeso y obesidad, lo que hace necesario definir variables más adecuadas para su correcto diagnóstico. Objetivo: comparar la categorización de sobrepeso y obesidad según el porcentaje de grasa medido con absorciometría de rayos X de energía dual (DEXA) con el IMC y la fórmula Clínica Universidad de Navarra - Body Adiposity Estimator (CUN-BAE), así como su relación con la adherencia a la dieta mediterránea, la actividad física y la satisfacción con la imagen corporal. Sujetos y métodos: estudio descriptivo transversal llevado a cabo en una muestra de 64 estudiantes de Medicina. Se determinaron peso, talla, perímetro de cintura, porcentaje de grasa medido con DEXA, adherencia a la dieta mediterránea, nivel de actividad física y satisfacción con la imagen corporal. Resultados: el IMC infradiagnostica sobrepeso respecto al porcentaje de grasa medido por DEXA mientras que la ecuación CUN-BAE presenta una buena correlación. El porcentaje de grasa se asocia inversamente con la satisfacción con la imagen corporal con mayor fuerza que el IMC. Conclusión: se necesitan nuevas herramientas capaces de distinguir los casos con IMC normal cuyo porcentaje de grasa corporal está elevado. Sería útil estudiar si el empleo de un cuestionario de satisfacción con la imagen corporal en personas clasificadas como normopeso podría distinguir a aquellas con una mayor probabilidad de exceso de grasa y así emplear estudios más exhaustivos en este colectivo.