Journal of the American College of Cardiology Vol. 62, No.

23, 2013
 2013 by the American College of Cardiology Foundation ISSN 0735-1097/$36.00
Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2013.08.1623

Heart Rhythm Disorders

The HAS-BLED Score Has Better Prediction

Accuracy for Major Bleeding Than CHADS2
or CHA2DS2-VASc Scores in Anticoagulated
Patients With Atrial Fibrillation
Vanessa Roldán, MD, PHD,* Francisco Marín, MD, PHD,y Sergio Manzano-Fernández, MD, PHD,y
Pilar Gallego, MD,* Juan Antonio Vílchez, PHD,y Mariano Valdés, MD, PHD,y
Vicente Vicente, MD, PHD,* Gregory Y. H. Lip, MDz
Murcia, Spain; and Birmingham, United Kingdom

Objectives The aim of this study was to test the hypothesis that a specific bleeding risk score, HAS-BLED (hypertension,
abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly,
drugs/alcohol concomitantly), was better at predicting major bleeding compared with CHADS2 (congestive heart
failure, hypertension, 75 years of age or older, diabetes mellitus, and previous stroke or transient ischemic attack)
and CHA2DS2-VASc (congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus, previous
stroke or transient ischemic attack, vascular disease, 65 to 74 years of age, female) in anticoagulated atrial
fibrillation (AF) patients.

Background The CHADS2 and CHA2DS2-VASc scores are well-validated stroke risk prediction scores for AF, but are also
associated with increased bleeding and mortality.

Methods We recruited 1,370 consecutive AF patients (49% male; median age, 76 years) receiving oral anticoagulation
therapy from our outpatient anticoagulation clinic, all of whom were receiving acenocoumarol and had an
international normalized ratio between 2.0 and 3.0 during the preceding 6 months. During follow-up, major bleeding
events were identified by the 2005 International Society on Thrombosis and Haemostasis criteria.
Model performance was evaluated by calculating the C-statistic, and the improvement in predictive accuracy
was evaluated by calculating the net reclassification improvement and integrated discrimination improvement.

Results After a median follow-up of 996 (range, 802 to 1,254) days, 114 patients (3.0%/year) presented with a major
bleeding event; 31 of these events were intracranial hemorrhages (0.8%/year). Based on the C-statistic, HAS-
BLED had a model performance superior to that of both CHADS2 and CHA2DS2-VASc (both p < 0.001).
Both net reclassification improvement and integrated discrimination improvement analyses also show that
HAS-BLED was more accurately associated with major bleeding compared with CHADS2 and CHA2DS2-VASc
scores.

Conclusions In anticoagulated AF patients, a validated specific bleeding risk score, HAS-BLED, should be used for assessing
major bleeding. The practice of using CHADS2 and CHA2DS2-VASc as a measure of high bleeding risk should be
discouraged, given its inferior predictive performance compared with the HAS-BLED score. (J Am Coll Cardiol
2013;62:2199–204) ª 2013 by the American College of Cardiology Foundation

From the *Hematology and Medical Oncology Unit, Hospital Universitario
Morales Meseguer, University of Murcia, Murcia, Spain; yDepartment of Cardi-
ology, Hospital Universitario Virgen de la Arrixaca, University of Murcia, Murcia,
Spain; and the zUniversity of Birmingham Centre for Cardiovascular Sciences,
City Hospital, Birmingham, United Kingdom. This work was partially supported
by Sociedad Española de Cardiología, RD06/0014/039, (RECAVA) from ISCIII,
and PI11/1256-FEDER from ISCIII. Dr. Roldán has received funding for
consultancy and lecturing from Bristol-Myers Squibb, Bayer, and Boehringer
Ingelheim. Dr. Marín has received funding for research, consultancy, and lecturing
from Abbott, Boston Scientific, Bayer, AstraZeneca, Daiichi Sankyo, Bristol-Myers
Squibb/Pfizer Inc., and Boehringer Ingelheim. Dr. Lip has received funding for
research, consultancy, and lecturing from different manufacturers of drugs used for
the treatment of atrial fibrillation, including AstraZeneca, Bayer, Boehringer
Ingelheim, Astellas, sanofi-aventis, and Daiichi Sankyo. All other authors have
reported that they have no relationships relevant to the contents of this paper to
disclose.
Manuscript received April 1, 2013; revised manuscript received August 17, 2013,
accepted August 26, 2013.
2200 Roldán et al. JACC Vol. 62, No. 23, 2013
HAS-BLED and Major Bleeding in Atrial Fibrillation December 10, 2013:2199–204

Abbreviations Oral anticoagulation (OAC) is Also, HAS-BLED has been related to major bleeding during
and Acronyms highly effective in reducing the bridging (20) and percutaneous coronary interventions
risk of stroke in atrial fibrillation (21,22) in both AF and non-AF cohorts.
AF = atrial fibrillation
(AF) patients (1). Decisions on In the present study, we tested the hypothesis that
CHADS2 = congestive heart
thromboprophylaxis have been a specific bleeding risk score, HAS-BLED, was better
failure, hypertension,
75 years of age or older, based on stroke risk, as assessed at predicting major bleeding compared with CHADS2
diabetes mellitus, and by different stroke risk stratifi- and CHA2DS2-VASc in anticoagulated AF patients.
previous stroke or transient cation schemes (2), such as the
ischemic attack
CHADS2 (congestive heart fail-
CHA2DS2-VASc = congestive Methods
ure, hypertension, 75 years of age
heart failure, hypertension,
75 years of age and older,
or older, diabetes mellitus, and Patients. We recruited consecutive patients with perma-
diabetes mellitus, previous previous stroke or transient is- nent or paroxysmal AF receiving OAC therapy from our
stroke or transient ischemic chemic attack) score (3). More outpatient anticoagulation clinic. We studied patients who
attack, vascular disease, were entered into our anticoagulation clinic database in 2007
recently, the CHA2DS2-VASc
65 to 74 years of age, female
(congestive heart failure, hyper- and the first trimester of 2008. The various clinical param-
CI = confidence interval
tension, 75 years of age and eters needed to calculate the HAS-BLED and CHA2DS2-
HAS-BLED = hypertension,
older, diabetes mellitus, previous VASc scores were available on our database, and, thus, the
abnormal renal/liver
function, stroke, bleeding
stroke or transient ischemic at- various scores were applied retrospectively to the cohort for
history or predisposition, tack, vascular disease, 65 to 74 the present analysis.
labile international years of age, female) score has All patients were receiving anticoagulation therapy with
normalized ratio, elderly, acenocoumarol and consistently achieved an international
been used in guidelines, with
drugs/alcohol
concomitantly
particular focus on the initial normalized ratio (INR) between 2.0 and 3.0 during the
HR = hazard ratio
identification of “truly low risk” previous 6 months of clinic visits. Patients with prosthetic
patients as the initial decision- heart valves, acute coronary syndrome, stroke (ischemic or
IDI = integrated
discrimination improvement
making step (2,4,5). embolic), valvular AF, or any hemodynamic instability as
Stroke risk and bleeding risk well as patients who had hospital admission or surgical
INR = international
normalized ratio are closely related, and the intervention in the preceding 6 months were excluded from
NRI = net reclassification
CHADS 2 score closely correlates the study. A complete medical history was recorded. Follow-
improvement with bleeding rate (6,7). This up was performed through visits to the anticoagulation clinic.
OAC = oral anticoagulation
has led to many clinicians occa- The HAS-BLED bleeding risk score (14) was calculated as
sionally using the CHADS2 (and a measure of baseline bleeding risk, as the result of adding 1
VKA = vitamin K antagonist
more recently CHA2DS2-VASc) point to hypertension, abnormal renal/liver function (1 point
as an indicator of bleeding risk, which could lead to the low each), stroke, bleeding history or predisposition, labile INR,
use of OAC in those with high CHADS2 (or CHA2DS2- elderly (65 years of age and older), and drugs/alcohol
VASc) scores (8–10). In some prescribing recommendations concomitantly (1 point for each one). Based on our inclusion
for the novel oral anticoagulants, the lower dose of, for ex- criteria at entry, labile INR was quantified as 0 in every patient.
ample, dabigatran is recommended at high bleeding risk as Baseline stroke risk was assessed using the CHADS2 and
quantified by a high CHADS2 score (11,12). CHA2DS2-VASc scores (3,4).
Specific bleeding risk scores are available for patients Major bleeding events were defined by the 2005 Interna-
with AF (13), and the HAS-BLED score is now recom- tional Society on Thrombosis and Haemostasis criteria (23).
mended in European and Canadian AF guidelines to estimate Statistical analysis. Continuous variables were tested for
major bleeding risk in anticoagulated AF patients (5,13–15). normality by the Kolmogorov-Smirnov test. Continuous
HAS-BLED (hypertension, abnormal renal/liver function, variables are presented as a mean  SD or median (inter-
stroke, bleeding history or predisposition, labile inter- quartile range, as appropriate, and categorical variables as
national normalized ratio, elderly, drugs/alcohol concomi- a percentage. Cox models were used to determine the
tantly) has been shown to perform better than other bleeding associations between clinical scores and bleeding as well as
risk scores (such as HEMORR2HAGES [Hepatic or Renal and mortality.
Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Model performance was evaluated by calculating C-statistic,
Platelet Count or Function, Re-Bleeding, Hypertension, and the improvement in predictive accuracy was evaluated by
Anemia, Genetic Factors, Excessive Fall Risk and Stroke], calculating the net reclassification improvement (NRI) and
ATRIA [Anticoagulation and Risk Factors in Atrial Fibril- integrated discrimination improvement (IDI), as described
lation]) for predicting serious bleeding in vitamin K antagonist by Pencina et al. (24), where the categories of probability for
(VKA) and non-VKA anticoagulated clinical trial cohorts of events are defined based on the HAS-BLED or CHADS2
AF patients (16), as well as real-world clinical practice (17,18). or CHA2DS2-VASc scores. We used the method described
HAS-BLED is also the only risk score predictive of intra- by Hanley and McNeil (25,26) for the comparison of cor-
cranial bleeding in AF (16) and non-AF (19) patients. related C-statistic.
JACC Vol. 62, No. 23, 2013 Roldán et al. 2201
December 10, 2013:2199–204 HAS-BLED and Major Bleeding in Atrial Fibrillation

A p value <0.05 was accepted as statistically significant. Cox Regression Analysis for the Composite of
Statistical analyses were performed using SPSS version Table 2
Major Hemorrhagic Events
15.0 for Windows (SPSS, Inc., Chicago, Illinois) and
Univariate Analysis Multivariate Analysis
SAS version 9.2 (SAS Institute Inc., Cary, North Carolina).
Age 65 yrs 1.71 (1.14–2.55); 0.009 1.57 (1.04–2.38); 0.032
Female 0.60 (0.41–0.87); 0.007 0.74 (0.50–1.11); 0.148
Results Hypertension 1.52 (0.88–2.62); 0.129 1.54 (0.88–2.68); 0.126
Diabetes 1.25 (0.84–1.87); 0.277
We included 1,370 patients (47% male; median age, 76 Previous stroke 1.80 (1.20–2.70); 0.005 1.52 (0.98–2.36); 0.060
years; interquartile range, 71 to 81 years) (Table 1). Median Coronary heart 1.70 (1.12–2.59); 0.012 1.50 (0.95–2.39); 0.084
follow-up was 996 days (interquartile range, 802 to 1,254 disease
Heart failure 1.20 (0.81–1.78); 0.352
days). During this period, 114 patients (3.0%/year) pre-
Renal 2.11 (1.30–3.43); 0.002 1.57 (0.96–2.59); 0.074
sented with a major bleeding event; of these, 31 were impairment
intracranial hemorrhages (0.8%/year). A total of 160 patients Previous bleeding 6.52 (4.40–9.66); <0.001 5.37 (3.57–8.07); <0.001
(4.3%/year) died during the follow-up, 18 (0.4%/year) as Current alcoholic 2.22 (1.12–4.39); 0.022 1.56 (0.75–3.24); 0.237
a result of a hemorrhage. consumption

Data on the CHA2DS2VASc and HAS-BLED scores Hepatic 3.57 (1.31–9.68); 0.013 3.09 (1.09–8.75); 0.034
impairment
of patients who experienced major bleeding events are
Antiplatelet 1.76 (1.16–2.67); 0.008 1.03 (0.64–1.67); 0.897
provided in Online Tables 1 and 2. The cumulative event therapy
rates are shown in Kaplan-Meier survival curves as Online HAS-BLED 1.94 (1.66–2.28);<0.001 d
Figures 1a and 1b. CHA2DS2-VASc 1.22 (1.09–1.37); 0.001 d
Univariate and multivariate analyses. In Table 2, we show score
CHADS2 1.31 (1.38–1.52); <0.001
the univariate and multivariate analyses, exploring the d

different variables associated with major bleeding events. Values are hazard ratio (95% confidence interval); p value. Because the risk factor components
of HAS-BLED, CHADS2, and CHA2DS2-VASc scores were entered into the multivariate analysis, the
On univariate analysis, the CHADS2 and CHA2DS2- scores themselves were not entered into the multivariate model.
VASc scores were predictive of bleeding events, with a CI ¼ confidence interval; HR ¼ hazard ratio; other abbreviations as in Table 1.

hazard ratio (HR): 1.31 (95% confidence interval [CI]:

1.14 to 1.52; p < 0.001) and an HR: 1.22 (95% CI: 1.09 to
Clinical Characteristics of the Studied Population
Table 1
(N ¼ 1,370)
1.37; p ¼ 0.001), respectively. The HAS-BLED score was
predictive of major bleeds, with an HR: 1.94 (95% CI: 1.66
Heart failure 433 (32) to 2.28; p < 0.001), which was higher than for the
History of stroke or TIA 364 (19) CHADS2 or CHA2DS2-VASc scores.
Coronary artery disease 254 (18)
On receiver-operating characteristic curve analyses,
Current alcoholic consumption 49 (4)
the HAS-BLED had a similar C-statistic (0.69  0.03;
Previous bleeding episode 111 (9)
p < 0.001) as the multivariable model (0.71  0.03;
Renal impairment 141 (10)
Liver impairment 18 (1)
p < 0.001) tested in Table 2. The C-statistics
HAS-BLED score 2 (2–3)
for HAS-BLED and the multivariable model were sig-
HAS-BLED 3 479 (35) nificantly higher than those for CHADS2 (0.59  0.03;
CHADS2 score 2 (2–3) p ¼ 0.002) or CHA2DS2-VASc (0.58  0.03; p ¼ 0.006)
CHADS2 2 1,027 (75) (both comparisons, p < 0.001) (Table 3).
CHA2DS2-VASc score 4 (3–5) On multivariate analysis, both CHADS2 and CHA2DS2-
CHA2DS2-VASc 2 1,289 (94) VASc scores lost their statistical significance after adjusting
Concomitant treatment by HAS-BLED score (Table 4).
Antiplatelet therapy 246 (18)
Predictive performance for major bleeding. As detailed in
ACE inhibitors/angiotensin receptor blockers 712 (52)
Table 3, the HAS-BLED score showed a model perfor-
Calcium antagonist 342 (25)
Beta-blockers 466 (34)
mance (based on C-statistics) superior to both that of
Statins 329 (24)
CHADS2 and CHA2DS2-VASc scores (both p < 0.001).
Digoxin 274 (20) Both NRI and IDI analyses show how the HAS-BLED
Diuretics 616 (45) score was more accurately associated with major bleeding
Values are n (%) or median (interquartile range).
episodes than to both the CHADS2 (both p < 0.001) and
ACE ¼ angiotensin-converting enzyme; CHADS2 ¼ congestive heart failure, hypertension, 75 CHA2DS2-VASc (all p values <0.001 for IDI and NRI).
years of age or older, diabetes mellitus, and previous stroke or transient ischemic attack; CHA2DS2-
VASc [ congestive heart failure, hypertension, 75 years of age and older, diabetes mellitus,
Based on reclassification analyses, the probability of
previous stroke or transient ischemic attack, vascular disease, 65 to 74 years of age, female; correctly predicting serious bleeding events using the HAS-
HAS-BLED: hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition,
labile international normalized ratio, elderly, drugs/alcohol concomitantly; TIA ¼ transient ischemic
BLED score was particularly reflected in the percentage of
attack. events correctly reclassified (Table 4).
2202 Roldán et al.
HAS-BLED and Major Bleeding in Atrial Fibrillation
Evaluating the Predictive Ability of the HAS-BLED Score Versus CHADS2 or CHA2DS2-VASc Score for the Detection of
Table 3
Major Bleeding Using C-Statistics, Relative NRI, and IDI Indexes
C-Statistic
(95% CI) p Value Relative IDI, %
CHADS2 0.59 (0.56–0.62)
HAS-BLED 0.69 (0.67–0.72) <0.001
CHA2DS2- 0.58 (0.55–0.60)
VASc
HAS-BLED 0.69 (0.67–0.72) <0.001
IDI ¼ integrated discrimination improvement; NRI ¼ net reclassification improvement; other abbreviations as in Tables 1 and 2.
Discussion
In this study, we confirm our hypothesis that the HAS-
BLED score had modest but significantly better prediction
accuracy than stroke stratification scores (CHADS2 and
CHA2DS2-VASc) for major bleeding events in antico-
agulated AF patients. Thus, a well-validated specific bleeding
risk score, HAS-BLED, should be used for assessing major
bleeding in AF patients. The practice of using CHADS2
and CHA2DS2-VASc scores as a measure of high bleeding
risk should thus be avoided due to its inferior predictive
performance compared with that of the HAS-BLED score.
The HAS-BLED bleeding score is a simple and useful
tool for application in daily clinical practice. Since its first
description in 2010 (14), this score has been validated in
several populations and has been shown to outperform
several older (and more complicated) bleeding risk scores
(16–19,27). In a recent analysis of an unselected nationwide
cohort of hospitalized patients with AF, for example, the
simple HAS-BLED score was comparable to the older
(and more complex) HEMORR2HAGES in predicting
bleeding risk (28). Similarly HAS-BLED has been de-
monstrated to be better than the new ATRIA risk score
(16–19).
Stroke risk is closely related to bleeding risk, and OAC
therapy needs to balance the benefit from stroke prevention
against serious bleeding risk. Many thromboembolic risk
factors have also been identified as bleeding risk factors, and
thus, risk factors for OAC-associated bleeding, are often also
indications for OAC use in AF patients as well (14,29). We
previously showed how the HAS-BLED bleeding score,
although having good predictive value for assessing major
bleeding risk in AF patients (performing as well as
Cox Regression Analysis: Predictive Value of CHADS2
Table 4 and CHA2DS2-VASc Scores for Bleeding Events by
Themselves and Adjusted by HAS-BLED Score
Univariate Analysis
HAS-BLED score 1.94 (1.66–2.27); <0.001
CHADS2 score 1.31 (1.14–1.52); <0.001
HAS-BLED score 1.94 (1.66–2.27); <0.001
CHA2DS2-VASc 1.22 (1.66–2.27); 0.001
score
Values are hazard ratio (95% confidence interval); p value.
Abbreviations as in Tables 1 and 2.
JACC Vol. 62, No. 23, 2013
December 10, 2013:2199–204
Events Correctly No Events Correctly
p Value NRI, % SD p Value Reclassified, % Reclassified, %
10 <0.001 38.26 7.30 <0.001 33.63 4.63
12 <0.001 37.60 7.81 <0.001 30.97 6.63
a multivariate model), was also modestly predictive of ad-
verse cardiovascular events and death in anticoagulated AF
patients (but HAS-BLED performed less well compared
with a multivariate model) (30). Indeed, the HAS-BLED
score has not been designed to predict thromboembolic
events, and for that purpose, the CHADS2 or CHA2DS2-
VASc scores have been demonstrated to be much better
(30,31).
Our analysis also suggests that there may be limited utility in
developing a stratification scheme for predicting both throm-
botic and bleeding events. Although all valid stratification
schemes (CHADS2/CHA2DS2-VASc and HAS-BLED)
share some risk factors in common, the HAS-BLED score
is clearly oriented toward predicting serious bleeding (previous
hemorrhagic episode, kidney or liver impairment, concomitant
aspirin/nonsteroidal anti-inflammatory drug use, labile INR).
Another advantage of the HAS-BLED score is that it is
relatively simple and user-friendly, yet offers useful predictive
capacity for bleeding and makes clinicians think about the
potentially reversible risk factors for bleeding.
Of note, the HAS-BLED score is recommended in major
guidelines (5,13,15) to “flag” patients potentially at risk
of bleeding and to make clinicians think about correcting
the potentially reversible bleeding risk factors. The guide-
lines strongly emphasize that a high HAS-BLED score
should not be used as a reason to withhold anticoagulation
therapy (5).
Study limitations. There could be some selection bias
because patients were on stable OAC therapy at entry (i.e.,
all INRs were 2.0 to 3.0 in the preceding 6 months to allow
for some population homogeneity at study entry), and, thus,
patients with unstable anticoagulation who are more prone
to have adverse events were excluded. Similarly, they were all
“experienced” patients with coumarin treatment. It is well
known that the risk of bleeding while receiving anti-
coagulation therapy or having a thromboembolic event is
highest during the period immediately after treatment with
coumarin is initiated (32). Nonetheless, it must not be
Multivariate Analysis
forgotten that even patients with stable OAC (i.e., with
2.02 (1.67–2.45); <0.001
nonlabile INRs) may sustain major bleeds (including intra-
0.94 (0.79–1.12); 0.488
cranial bleeding), and numerous studies show how labile
2.02 (1.67–2.45); <0.001
0.96 (0.83–1.10); 0.566
INRs are related to increased bleeding risk (33).
Indeed, our observed greater importance of previous
bleeding and liver dysfunction components in the develop-
ment of major bleeds is of interest, but this should be
JACC Vol. 62, No. 23, 2013
December 10, 2013:2199–204
confirmed with other large cohorts, especially because our
real-world patients would have been initially selected as
being (probably) suitable for the initiation of anticoagulation
and hence referred to our anticoagulation clinic. Nonethe-
less, the strength of our study is its inclusion of consecutive
patients attending our anticoagulation clinic, and even when
avoiding 1 point on the HAS-BLED score due to the labile
INR criterion in our well-controlled VKA cohort, this score
still maintains its predictive power of major bleeding events.
Conclusions
We have demonstrated that the predictive value and
usefulness of the HAS-BLED score for predicting major
bleeding is better than that of the CHADS2 or CHA2DS2-
VASc scores, in a large cohort of consecutive patients taking
acenocoumarol. The use of CHADS2 and CHA2DS2-
VASc as a measure of high bleeding risk in AF should
be discouraged, given its inferior predictive performance
compared with the HAS-BLED score. Thus, a well-
validated specific bleeding risk score, HAS-BLED, should
be used for assessing major bleeding in anticoagulated AF
patients.
Reprint requests and correspondence: Prof. Gregory Y. H. Lip,
University of Birmingham Centre for Cardiovascular Sciences, City
Hospital, Dudley Road, Birmingham B18 7QH, United Kingdom.
E-mail: g.y.h.lip@bham.ac.uk.
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Key Words: anticoagulation - bleeding - risk prediction - stroke.
APPENDIX
For supplemental tables and figures, please see the online version of this
article.