BackgroundTherapeutic decisions in atrial fibrillation (AF) are often influenced by assessment of bleeding risk. However, existing bleeding risk scores have limitations.ObjectivesWe sought to develop and validate a novel bleeding risk score using routinely available clinical information to predict major bleeding in a large, community-based AF population.MethodsWe analysed data from Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF), a prospective registry that enrolled incident and prevalent AF patients at 176 US sites. Using Cox proportional hazards regression, we identified factors independently associated with major bleeding among patients taking oral anticoagulation (OAC) over a median follow-up of 2 years (interquartile range = 1.6–2.5). We also created a numerical bedside risk score that included the five most predictive risk factors weighted according to their strength of association with major bleeding. The predictive performance of the full model, the simple five-item score, and two existing risk scores (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile INR, elderly, drugs/alcohol concomitantly, HAS-BLED, and anticoagulation and risk factors in atrial fibrillation, ATRIA) were then assessed in both the ORBIT-AF cohort and a separate clinical trial population, Rivaroxaban Once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET-AF).ResultsAmong 7411 ORBIT-AF patients taking OAC, the rate of major bleeding was 4.0/100 person-years. The full continuous model (12 variables) and five-factor ORBIT risk score (older age [75+ years], reduced haemoglobin/haematocrit/history of anaemia, bleeding history, insufficient kidney function, and treatment with antiplatelet) both had good ability to identify those who bled vs. not (C-index 0.69 and 0.67, respectively). These scores both had similar discrimination, but markedly better calibration when compared with the HAS-BLED and ATRIA scores in an external validation population from the ROCKET-AF trial.ConclusionsThe five-element ORBIT bleeding risk score had better ability to predict major bleeding in AF patients when compared with HAS-BLED and ATRIA risk scores. The ORBIT risk score can provide a simple, easily remembered tool to support clinical decision making.

BACKGROUND Classification of chronic heart failure (HF) is based on criteria that may not adequately capture disease heterogeneity. Improved phenotyping may help inform research and therapeutic strategies. OBJECTIVE This study used cluster analysis to explore clinical phenotypes in chronic HF patients. METHODS A cluster analysis was performed on 45 baseline clinical variables from 1,619 participants in HF-ACTION (Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training), evaluating exercise training versus usual care in chronic systolic HF. Association between identified clusters and clinical outcomes was performed using Cox proportional hazards modeling. Differential associations between clinical outcomes and exercise testing were examined using interaction testing. RESULTS Ranging in size from 248 to 773, four clusters were identified whose patients varied considerably along measures of age, sex, race, symptoms, comorbidities, HF etiology, socioeconomic status, quality of life, cardiopulmonary exercise testing parameters, and biomarker levels. Differential associations were observed for hospitalization and mortality risks between and within clusters. To illustrate, compared with cluster 1, risk of all-cause mortality/all-cause hospitalization ranged from 0.65 (0.54 to 0.78) for cluster 4 to 1.02 (0.87 to 1.19) for cluster 3. However, for all-cause mortality, cluster 3 had disproportionately lower risk 0.61 (0.44 to 0.86). Evidence suggested differential effects of exercise treatment on changes in peak VO2 and clinical outcomes between clusters (p for interaction <0.04). CONCLUSIONS Cluster analysis of clinical variables identified 4 distinct phenotypes of chronic HF. Our findings underscore the high degree of disease heterogeneity that exists within chronic HF patients and a need for improved phenotyping.

Among patients with atrial fibrillation who had experienced an acute ischemic stroke, inadequate therapeutic anticoagulation preceding the stroke was prevalent. Therapeutic anticoagulation was associated with lower odds of moderate or severe stroke and lower odds of in-hospital mortality.

No abstract