Performance of the HEMORR2HAGES, ATRIA, and HAS-BLED Bleeding Risk-Prediction Scores in Patients With Atrial Fibrillation Undergoing Anticoagulation: The AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) Study

Study Questions:

What is the relative predictive value of three validated risk estimation tools derived in cohorts of atrial fibrillation patients to predict bleeding risk associated with anticoagulation?


The authors presented an analysis of data from the AMADEUS (Evaluating the Use of SR34006 Compared to Warfarin or Acenocoumarol in Patients With Atrial Fibrillation) trial, a multicenter, randomized, open label noninferiority study comparing idraparinux with adjusted-dose oral vitamin K antagonist therapy in patients with atrial fibrillation. The study principal safety outcome was a composite of major bleeding plus clinically relevant nonmajor bleeding. The prognostic value of three risk scores derived in anticoagulated atrial fibrillation patient populations (HEMORR2HAGES, ATRIA, and HAS-BLED) was determined using Cox proportional hazards analysis. Net reclassification improvement and decision-curve analysis quantified the clinical usefulness of each prediction model.


The HAS-BLED score had the highest net reclassification improvement for predicting clinically relevant bleeding (10.3% and 13% improvement compared with HEMORR2HAGES and ATRIA, respectively). The HAS-BLED score also performed best by receiver-operating characteristic (ROC) analysis (C-indices: 0.60 vs. 0.55 and 0.50 for HAS-BLED vs. HEMORR2HAGES and ATRIA, respectively). The HAS-BLED was superior to the other two scores on decision-curve analysis, and was the only score that significantly predicted intracranial hemorrhage (C-index, 0.75; p = 0.03).


The authors concluded that all three bleeding risk-prediction scores demonstrated only modest performance in predicting any clinically relevant bleeding, although the HAS-BLED score performed better than the HEMORR2HAGES and ATRIA scores, based on ROC analysis, reclassification analysis, and decision-curve analysis. The authors observed that only HAS-BLED demonstrated a significant predictive performance for intracranial hemorrhage. The authors opined that both its simplicity and improved performance may make the HAS-BLED score an attractive method for estimating oral anticoagulant-related bleeding risk in clinical practice, as recommended in international guidelines.


Although much has been written about the importance of estimating thromboembolism or stroke risk in atrial fibrillation in order to determine the potential benefit from anticoagulation, too little attention has been paid to the other side of the clinical decision-making equation: estimating individual bleeding risk associated with anticoagulation in atrial fibrillation. The HAS-BLED score appears to provide clinicians with the best clinical estimate of bleeding risk associated with warfarin use in atrial fibrillation, in spite of only modest predictive performance (C-index, 0.60). Both the European Society of Cardiology and Canadian guidelines recommend the use of the HAS-BLED score in atrial fibrillation management guidelines. The current study should provide evidence to support that recommendation. It seems downright illogical not to use this tool, along with stroke risk tools, to estimate both risk and benefit of warfarin anticoagulation during clinical decision-making in atrial fibrillation.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Risk, Oligosaccharides, Warfarin, Canada, Fibrinolytic Agents, Thromboembolism, Blood Coagulation, Intracranial Hemorrhages, Cardiology, Atrial Fibrillation, Hemorrhage, Oral Hemorrhage

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