OBJECTIVES
The objective of this study was to compare the predictive performance of bleeding risk-estimation tools in a cohort of patients with atrial fibrillation (AF) undergoing anticoagulation.
BACKGROUND
Three bleeding risk-prediction schemes have been derived for and validated in patients with AF: HEMORR(2)HAGES (Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke), ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation), and HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, Drugs/Alcohol). Τhe relative predictive values of these bleeding scores have not previously been compared.
METHODS
We analyzed the dataset 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 that compared fixed-dose idraparinux with adjustable-dose oral vitamin K antagonist therapy in patients with AF. The principal safety outcome was any clinically relevant bleeding event, which was a composite of major bleeding plus clinically relevant nonmajor bleeding.
RESULTS
The HAS-BLED score performed best in predicting any clinically relevant bleeding, reflected both in net reclassification improvement (10.3% and 13% improvement compared with HEMORR(2)HAGES and ATRIA, respectively) and receiver-operating characteristic (ROC) analyses (c-indexes: 0.60 vs. 0.55 and 0.50 for HAS-BLED vs. HEMORR(2)AGES and ATRIA, respectively). Using decision-curve analysis, the HAS-BLED score demonstrated superior performance compared with ATRIA and HEMORR(2)HAGES at any threshold probability for clinically relevant bleeding. HAS-BLED was the only score that demonstrated a significant predictive performance for intracranial hemorrhage (c-index: 0.75; p = 0.03). An ATRIA score >3 was not significantly associated with the risk for any clinically relevant bleeding on Cox regression or on ROC analysis (c-index: 0.50; p = 0.87).
CONCLUSIONS
All 3 tested bleeding risk-prediction scores demonstrated only modest performance in predicting any clinically relevant bleeding, although the HAS-BLED score performed better than the HEMORR(2)HAGES and ATRIA scores, as reflected by ROC analysis, reclassification analysis, and decision-curve analysis. Only HAS-BLED demonstrated a significant predictive performance for intracranial hemorrhage. Given its simplicity, the HAS-BLED score may be an attractive method for the estimation of oral anticoagulant-related bleeding risk for use in clinical practice, supporting recommendations in international guidelines.
[1]
D. Stott,et al.
RCPE UK Consensus Conference on 'approaching the comprehensive management of atrial fibrillation: evolution or revolution?'.
,
2012,
The journal of the Royal College of Physicians of Edinburgh.
[2]
N. Cook.
Use and Misuse of the Receiver Operating Characteristic Curve in Risk Prediction
,
2007,
Circulation.
[3]
P. Loewen,et al.
Risk of bleeding with oral anticoagulants: an updated systematic review and performance analysis of clinical prediction rules
,
2011,
Annals of Hematology.
[4]
Gregory Y H Lip,et al.
A novel user-friendly score (HAS-BLED) to assess 1-year risk of major bleeding in patients with atrial fibrillation: the Euro Heart Survey.
,
2010,
Chest.
[5]
Stanley Nattel,et al.
Focused 2012 update of the Canadian Cardiovascular Society atrial fibrillation guidelines: recommendations for stroke prevention and rate/rhythm control.
,
2012,
The Canadian journal of cardiology.
[6]
S. Lévy,et al.
Comparison of idraparinux with vitamin K antagonists for prevention of thromboembolism in patients with atrial fibrillation: a randomised, open-label, non-inferiority trial
,
2008,
The Lancet.
[7]
G. Lip,et al.
Relation of the HAS-BLED Bleeding Risk Score to Major Bleeding, Cardiovascular Events, and Mortality in Anticoagulated Patients With Atrial Fibrillation
,
2012,
Circulation: Arrhythmia and Electrophysiology.
[8]
P. Kirchhof,et al.
Bleeding risk assessment and management in atrial fibrillation patients
,
2011,
Thrombosis and Haemostasis.
[9]
M. Rich,et al.
Clinical classification schemes for predicting hemorrhage: results from the National Registry of Atrial Fibrillation (NRAF).
,
2006,
American heart journal.
[10]
D. Singer,et al.
A new risk scheme to predict warfarin-associated hemorrhage: The ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) Study.
,
2011,
Journal of the American College of Cardiology.