Comparison between beta-blockers and calcium channel blockers in patients with atrial fibrillation according to renal function.

BACKGROUND: Rate control is the most commonly employed first-line management strategy for atrial fibrillation (AF) in patients with chronic kidney disease (CKD). Principal agents used to control heart rate (HR) include beta-blockers (BB) and nondihydropyridine calcium channel blockers (ND-CCB). However, there is a paucity of published studies of the differences between those drugs in CKD patients. HYPOTHESIS: The present study aimed to investigate the differences, in terms of hospitalizations due to a poor HR control, in patients with AF under a rate-control strategy according to glomerular filtration rate (GFR). METHODS: The study cohort included 2804 AF patients under rate-control regime (BB or ND-CCB) between January 2014 and April 2020. The end point, determined by competing risk regression, was hospitalizations for AF with rapid ventricular response (RVR), slow ventricular response (SVR), and need for pacemaker. RESULTS: On multivariate analysis, there were no statistical differences between ND-CCB and BB for subjects with GFR > 60 mL/min/1.73 m2 (subdistribution heart rate [sHR] 0.850, 95% confidence interval [CI]: 0.61-1.19; p = .442) and GFR 30-59 mL/min/1.73 m2 (sHR 1.242, 95% CI: 0.80-1.63; p = .333), while in patients with GFR < 30 mL/min/1.73 m2, ND-CCB therapy was associated with increased hospitalizations due to poor HR control (sHR 4.53, 95% CI: 1.19-17.18; p = .026). CONCLUSION: In patients with GFR ≥ 30 mL/min/1.73 m2, the choice of ND-CCB or BB had no impact on hospitalizations due to poor HR control, while in GFR < 30 mL/min/1.73 m2, a possible association was detected. The effects of these drugs on GFR < 30 mL/min/1.73 m2 would require further investigation.

Is pre-diabetes a predictor of events in patients with atrial fibrillation?

BACKGROUND: Diabetes mellitus (DM) increases the probability of presenting atrial fibrillation (AF) and it is a predictor of its ischemic stroke. There is limited information of the association between glycated hemoglobin (HbA1c) levels and ischemic, embolic or bleeding events in patients with pre-DM and AF. METHODS: To investigate whether the presence of pre-DM in patients with AF predicts ischemic or bleeding events, myocardial infarction or mortality, we performed a retrospective study with a final cohort of 2993 non-diabetic patients with AF and data of glycated hemoglobin (HbA1c). We divided the cohort in two groups: those with normal glucose (n = 1351) and those with pre-diabetes (n = 1642). Incidence rates were calculated as the number of events per 100 person-years and were then compared between groups. Competitive hazard regression analysis for non-fatal events(death as the competing event) and conventional Cox regression for mortality were performed. RESULTS: There was not difference between groups for incidence rates of the different events per 100 person-years. Even considering HbA1c as continuous variable, the unadjusted analysis showed no relation between levels of HbA1c and more risk of events. This association remained not significant after adjustment for CHA2DS2-VASc score, HAS-BLED score and anticoagulation therapy. CONCLUSION: In this study of 2993 non-diabetic patients with new-onset AF, we have not found an association between HbA1c and worse prognosis when it is in the range of pre-diabetes.

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.

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.

Validation of Embolic and Bleeding Risk Scores in Patients With Atrial Fibrillation and Cancer.

Little is known about the prediction of atrial fibrillation (AF) risk scores in patients with cancer. The aim of this study was to assess the predictive ability of the CHA2DS2-VASc and HAS-BLED scores in patients with AF and cancer. Overall, 16,056 patients with AF diagnosed between 2014 and 2018 from a Spanish health area, including 1,137 patients with cancer, were observed during a median follow-up of 4.9 years. Although discrimination was similar between patients with cancer and patients without cancer who were treated with anticoagulation therapy (0.56 and 0.58), in patients with cancer who were not treated with anticoagulation therapy, c-statistic of CHA2DS2-VASc was poor and significantly lower than in the patients without cancer (0.42 vs 0.65). The overall precision of the CHA2DS2-VASc score was good throughout the follow-up (Brier score < 0.1), in patients with and without cancer. Regarding the HAS-BLED score, calibration and discrimination were poor in patients with cancer (c-statistic 0.51), similar to those in patients without cancer (c-statistic 0.53). In patients with cancer who were not treated with anticoagulation therapy, the embolic risk CHA2DS2-VASc score = 1 was similar to CHA2DS2-VASc score ≥ 2. Only patients with AF and cancer and CHA2DS2-VASc score = 0 presented a low risk of embolic events (negative predictive value 100%). A HAS-BLED score > 3 was not associated with higher bleeding risk in patients with cancer (p > 0.05). In summary, in patients with cancer and with AF, neither the CHA2DS2-VASc score nor the HAS-BLED score was useful for predicting embolic and hemorrhagic events, respectively. However, a CHA2DS2-VASc score 0 is useful to identify patients with AF and cancer who are at low embolic risk.

Incidence and Predictors of Bleeding in Patients With Cancer and Atrial Fibrillation.

Despite patients with cancer having a higher incidence of atrial fibrillation (AF), little is known about the predictors of outcomes in this population. This study aimed to assess the incidence and predictors of bleeding in patients with AF and cancer. The study population comprised 16,056 patients from a Spanish health area diagnosed with AF between 2014 and 2018 (1,137 with cancer). Competing risk analysis were used to evaluate the association of cancer and bleeding. Discrimination and calibration of bleeding risk scores were assessed by the concordance statistic and the Brier score, respectively. During a median follow-up of 4.9 years, the incidence of bleeding in patients with cancer was 13.2 per 100 patients/year. After multivariate adjustment, a significant association between cancer and bleeding was detected (subdistribution hazard ratio [sHR] 1.18, 95% CI 1.07 to 1.30, p = 0.001), specifically in patients with active cancer or previous radiotherapy. Early age, male gender, diabetes, and anticoagulation were independent predictors of bleeding. However, only anticoagulation with vitamin K antagonist (sHR 1.36, 95% CI 1.03 to 1.78, p = 0.026), not with direct oral anticoagulants (sHR 1.25, 95% CI 0.84 to 1.85, p = 0.270), was associated with bleeding. Discrimination and calibration of Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly, and Drugs/alcohol concomitantly (HAS-BLED), AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA), and Hepatic or renal disease, Ethanol abuse, Malignancy, Older (age ≥75 years), Reduced platelet count or function, Rebleeding risk, Hypertension, Anaemia, Genetic factors, Excessive fall risk and Stroke (HEMORR2HAGES) scores were poor in patients with cancer (concordance statistic <0.6 and Brier score >0.1). In summary, cancer was associated with an increased risk of bleeding in patients with AF. The predictive ability of bleeding risk scores was poor in this population. Anticoagulation with vitamin K antagonist but not with direct oral anticoagulants, was an independent predictor of bleeding in patients with cancer.