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.

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.

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.

Effect of mitral regurgitation on stroke risk in patients with non-rheumatic atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) carries a thrombotic risk related to blood stasis in the left atrium. In patients with rheumatic valve disease and AF, the presence of severe mitral regurgitation (MR) has been shown to reduce the risk of atrial thrombosis and stroke. However, in patients without rheumatic disease, the results are controversial. AIM: To analyse the association between MR and the incidence of stroke in patients with non-rheumatic AF. METHODS: We analysed data from the retrospective CardioCHUVI-AF registry, which includes 15,720 patients with AF (without mechanical prostheses or rheumatic valvular disease) in the Vigo area of Spain, during 2014-2018. We grouped the patients according to MR grades: 0-2 (n=15,194) and 3-4 (n=526). We performed univariate and multivariable competitive risk analyses to analyse the association between MR and stroke, with death as the competitive event. RESULTS: During a median (interquartile range [IQR]) follow-up of 4.9 (2.8-4.9) years, 859 patients (5.5%) suffered a stroke. The stroke incidence was 1.3 per 100 person-years (95% confidence interval [95% CI]: 1.2-1.4), with no difference between the MR groups. In univariate analysis, no relationship was observed between MR grade and stroke (subdistribution hazard ratio [sHR]: 1.12, 95% CI: 0.79-1.60; P=0.53); likewise after multivariable analysis (sHR: 0.98, 95% CI: 0.68-1.41; P=0.90). This same relationship was evaluated in subgroups of interest (patients with and without: oral anticoagulation, CHA2DS2-VASc≥2, prior heart failure, aortic valve disease, left ventricular ejection fraction≤40%, and moderate-severe left atrial dilation), with results consistent with the overall population. CONCLUSION: In our large registry of patients with non-rheumatic AF, we did not find a protective effect of grade 3-4 MR on the risk of stroke.

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.