Usefulness of the CHA2DS2-VASC Score to Predict Adverse

Outcomes in Patients Having Percutaneous Coronary

Intervention
Katia Orvin, MD*, Tamir Bental, MD, Abid Assali, MD, Eli Israel Lev, MD, Hana Vaknin-Assa, MD,
and Ran Kornowski, MD

The application of the CHA2DS2-VASC score as a novel risk stratication tool for pre-
dicting outcome in clinical applications other than atrial brillation and stroke prevention
has been previously examined. However, its usefulness in a population of patients with
coronary artery disease after percutaneous coronary intervention (PCI) has not been
explored. We investigated 12,785 consecutive patients who underwent PCI in a tertiary
medical center from April 2004 to August 2014 (mean follow-up 6.5 years) and computed
the CHA2DS2-VASC score on their index PCI. We assessed the relation between the
CHA2DS2-VASC score and clinical outcomes (for example, all-cause mortality and mor-
tality or myocardial infarction) at 1 and 5 years. The mean CHA2DS2-VASC score was 3.7
1.7, 59.1% of patients obtained a score of 3 to 5. Both the primary and secondary outcomes
at 1 and 5 years were signicantly more frequent as the CHA2DS2-VASC score increased.
Overall, the mortality rate after PCI was 10 times higher for patients with a CHA2DS2-
VASC score of 5 compared with a score of 1 at both 1-and 5-year follow-up. The CHA2DS2-
VASC score predicted all-cause mortality and death or nonfatal myocardial infarction in a
signicant (p <0.001, C-index 0.73 and 0.72) and linear fashion. In conclusion, the
CHA2DS2-VASC score can be used as a simple and effective tool to predict long-term
clinical outcomes in patients undergoing PCI. 2016 Elsevier Inc. All rights reserved.
(Am J Cardiol 2016;117:1433e1438)

Although risk scores, such as the Society of Thoracic Methods

Surgeons score and EuroSCORE to estimate the perioper-
The study population comprised all consecutive patients
ative risk of complications from coronary artery bypass
(n 12,785) who underwent PCI at our institution at the 2
grafting1,2 and Synergy between percutaneous coronary
hospitals of the Rabin Medical Center in Israel from April
intervention (PCI) with Taxus and Cardiac Surgery (SYN-
2004 to August 2014. We computed the CHA2DS2-VASC
TAX) score to predict adverse ischemic events in patients
score on their index PCI (rst PCI), regardless of having AF.
undergoing PCI3 have been widely used, other risk score for
Data collection was approved by the hospital ethics com-
the evaluation of clinical outcome after PCI (clinical
mittee in compliance with the Declaration of Helsinki. As
SYNTAX, SYNTAX II, the National Cardiovascular
we have previously reported,8,9 all data regarding the index
Database Registry CathPCI, and the ACEF [age, creatinine,
and subsequent procedures, as well as clinical and echo-
ejection fraction] model) are less widely used in clinical
cardiographic data, were extracted from the patients elec-
daily practice4e7 because of complex calculation, interob-
tronic medical records. Demographic data and death dates
server and intraobserver variability. Our aim was to inves-
were obtained from the medical centers demographic in-
tigate the predictive value of CHA2DS2-VASC (congestive
formation system, which is linked to the State of Israel
heart failure [CHF], hypertension, age
75 years, diabetes,
Ministry of Interior data system and the Clalit Health Or-
previous stroke, vascular disease, age 65 to 74 years, gender
ganization data warehouse. The accuracy of the mortality
[female] category) score as a simple tool for risk stratica-
data was veried with the Israel Central Bureau of Statistics.
tion of patients with PCI, regardless of atrial brillation
All data regarding previous and subsequent hospitalizations,
(AF), in a large all-comer PCI cohort.
including all International Classication of Diseases, Ninth
Revision, diagnoses, were retrieved from the medical cen-
ters data warehouse. Laboratory data were retrieved from
the medical centers central laboratory database. All follow-
up data were collected up to August 31, 2014.
Cardiology Department, Rabin Medical Center, Petach-Tikva, Sack-
Based on the CHA2DS2-VASC score, patients were given
ler Faculty of Medicine, Tel-Aviv University, Israel. Manuscript received
November 19, 2015; revised manuscript received and accepted February 8,
1 point for CHF, hypertension, age 65 to 74 years, diabetes
2016. mellitus, vascular disease, and female gender and 2 points
See page 1437 for disclosure information. for age 75 years or older and previous stroke.10 All patients
*Corresponding author: Tel: (972) 3-9377108; fax: (972) 3-9213221. had at least a score of 1 because all of them underwent PCI,
E-mail address: katiaorvin@gmail.com (K. Orvin). thus, they suffered from vascular atherosclerosis.

0002-9149/16/$ - see front matter 2016 Elsevier Inc. All rights reserved. www.ajconline.org
http://dx.doi.org/10.1016/j.amjcard.2016.02.010
1434 The American Journal of Cardiology (www.ajconline.org)

Table 1
Baseline characteristics
Variable Total cohort
(n12,785)

Age (years) 68.512.2

Men 76.2%
Diabetes mellitus 43.1%
Hypertension 73.2%
Smoker 34.8%
Prior stroke 5.6%
Prior atrial brillation 10.2%
eGFR ( ml/min/1.73m2)* 82.1 27.3
Creatinine (mg/dl) 1.10.8
Prior coronary bypass 14.1%
Prior heart failure 9.1%
Moderate/severe LV dysfunction 12.6%
Clinical Presentation
Figure 2. The frequency of the CHA2DS2-VASC score components.
MI or ACS 60.5%
Vascular dis. vascular disease.
ST-elevation MI 7.0%
Stable angina pectoris 39.5%
No. of coronary artery anomalies Table 2
1 23.4% Clinical outcome according to the CHA2DS2-VASC score
>2 43.4%
Single vessel PCI 84.3% CHA2DS2-VASC All-cause All-cause All-cause All-cause
Intervention in proximal vessel segment 44.1% score mortality mortality mortality mortality
Unprotected LM intervention 2.1% 1-year Non-fatal MI 5-years non-fatal MI
Drug eluting stent 47.2% 1-year 5-years
Bare metal stent 48.2%
1 1.0% 2.1% 2.5% 4.3%
Drug eluting balloon 0.2%
2 2.4% 3.8% 4.3% 7.4%
Balloon angioplasty 4.5%
3 3.7% 5.1% 8.9% 11.6%
4 6.1% 7.8% 17.4% 20.4%
ACS acute coronary syndrome; eGFR estimated glomerular ltration
5 10.7% 13.3% 25.9% 29.8%
rate; LM left main; LV left ventricle; MDRD = Modication of Diet in Renal
6 12.5% 16.6% 33.1% 37.4%
Disease; MI myocardial infarction; PCI percutaneous coronary intervention.
* MDRD was used for eGFR calculation. 7 15.2% 20.1% 39.4% 45.3%
8 22.2% 27.8% 53.5% 57.2%
9 19.2% 34.6% 39.5% 51.0%

MI myocardial infarction.

mortality or nonfatal myocardial infarction (MI) at 1-and 5-

Figure 1. The CHA2DS2-VASc score distribution in the entire cohort. The
score was calculated on the index (rst) PCI.
year follow-up as the secondary end points.
Baseline parameters were compared between groups
using the Student t test for continuous variables and the
chi-square test for categorical variables. Continuous var-
iables were tested with the KolmogoroveSmirnov test and
found to have a normal distribution. The survival analysis
was dened from the day of the index PCI. Survival
curves were constructed using the KaplaneMeier proce-
dure with log-rank testing of signicance. Survival tables
were constructed using lifetable analysis. For the
CHA2DS2-VASC scores predictive discrimination capa-
bility, a C-index was computed from Cox analysis using
an adaptation of the method proposed by Pencina et al11
and of the programming algorithm of Liu et al.12 Statis-
tical analyses were performed using IBM SPSS version 20
(IBM Corporation, Armonk, New York). All tests were 2-
tailed, and p <0.05 was considered signicant.

Results
We assessed the relation between CHA2DS2-VASC score
and clinical outcome which included all-cause mortality at A total of 12,785 patients (mean age 68.5  12.2 years,
1-and 5-year follow-up as the primary end points and 76.2% men) were evaluated for CHA2DS2-VASC score at
 Coronary Artery Disease/CHA2DS2-VASC Score in Patients with PCI 1435

Figure 3. KaplaneMeier survival curves as stratied for CHA2DS2-VASC score for the entire cohort. Patients with increased score had signicantly reduced
survival (A) and signicantly reduced event-free survival from combined end points including death and nonfatal MI (B).

Table 3 The differences in clinical variables between patients with

Comparison of CHA2DS2-VASC score component frequency in patients and without death and/or MI during follow-up are presented
with stable versus ACS in Supplementary Table 1.
CHA2DS2-VASC Stable coronary ACS patients P value The CHA2DS2-VASC score predicted all-cause mortality
componnts patients (n7729) and death or nonfatal MI in a signicant (p <0.001) and
(n5056) linear fashion as shown in Figure 3. The C-index mea-
CHF 887 (17.5%) 1606 (20.8%) <0.001
surements of the predictive power of the score were 0.73
Hypertension 3950 (78.1%) 5439 (70.4%) <0.001 (95% CI 0.7 to 0.76) for mortality and 0.72 (95% CI 0.69 to
Age
75 years 1915 (37.9%) 2631 (34.0%) <0.001 0.75) for death or nonfatal MI. The proportional risk
Diabetes mellitus 2385 (47.2%) 3124 (40.4%) <0.001 conferred by each point of the CHA2DS2-VASC score was
Stroke 236 (4.7%) 483 (6.2%) <0.001 of 1.545 (95% CI 1.507 to 1.584), with a C-statistic of 0.73
Age 65-74 years 1521 (30.1%) 1980 (25.6%) <0.001 (95% CI 0.7 to 0.76).
Women 1176 (23.3%) 1865 (24.1%) 0.26 In a multivariate Cox adjusted model including
CHA2DS2-VASC and the clinical variables not included in
ACS acute coronary syndrome; CHF congestive heart failure.
the score, the performance of the CHA2DS2-VASC score
was maintained (Supplementary Tables 2 and 3).
We compared the predictive ability of the CHA2DS2-
their index PCI. Most patients, 7,729 (60.5%), presented VASC score to the simple and available ACEF score (age/
with acute coronary syndrome (ACS), of which 894 (11.6%) ejection fraction 1 [if serum creatinine was >2.0 mg/dl]).
had ST elevation MI. Patients demographic, clinical, and We were able to calculate the ACEF score in 7,791 patients
angiographic features at the index PCI are listed in Table 1. (61% of the cohort). When testing for prediction of all-
A previous diagnosis of AF was present in only 1,309 pa- cause mortality, the ACEF score was predictive, with a
tients (10.2%). C-statistic of 0.65 (95% CI 0.61 to 0.69). Using a Cox
The mean CHA2DS2-VASC score was 3.7  1.7 (range 1 analysis, the proportional risk conferred by each point of the
to 9). The CHA2DS2-VASC score distribution at the index ACEF score was of 3.134 (95% CI 2.85 to 3.442). We
PCI is presented in Figure 1. Most of the patients (59.1%) wanted to test whether the risk conferred by the ACEF
had a CHA2DS2-VASC score of 3 to 5 with the most score is incremental as in the CHA2DS2-VASC score. We
frequent score of 4 obtained in 2,762 patients (21.6%). The therefore classied the patients into 9 groups by the per-
frequency of the CHA2DS2-VASC score individual com- centiles of the ACEF score and performed a KaplaneMeier
ponents are presented in Figure 2. analysis (Supplementary Figure 1). In the lower percentiles,
The median follow-up time was 6.4 years (range the change in risk was not incremental although overall the
3.5 months to 10.6 years). Both the primary and secondary score was predictive.
outcomes during follow-up increased linearly with elevated We performed a separate analysis according to the
score (Table 2). Overall, the mortality rate after PCI was 10 clinical presentation: patients with stable coronary versus
times greater for patients with a CHA2DS2-VASC score of 5 ACS. The individual components of the CHA2DS2-VASC
compared with a score of 1 at both 1-and 5-year follow-up. score were compared between the patients with stable and
1436 The American Journal of Cardiology (www.ajconline.org)

Figure 4. KaplaneMeier survival curves for all-cause mortality as stratied for CHA2DS2-VASC score in patients with ACS (A) versus stable patients (B).

Figure 5. Kaplan-Meier survival curves for combined end points of death and nonfatal MI as stratied for CHA2DS2-VASC score in patients with ACS (A)
versus stable patients (B).

ACS (Table 3). The CHA2DS2-VASC score predicted all-
cause mortality and death or nonfatal MI in a signicant
(p <0.001) and graded manner for patients with both stable
and ACS with a similar trend (Figures 4 and 5).
Discussion
This study demonstrated the CHA2DS2-VASC score
utility as a simple yet powerful tool to aid the prediction of
outcome in patients with PCI. Mortality risk in patients with
both stable coronary artery disease and ACS were found to
be well correlated with the score level. In contrast to other
available PCI risk stratication tools, the CHA2DS2-VASC
score is a simple and accustomed scoring tool and therefore
may be easily applied in daily practice.
The CHADS2 and CHA2DS2-VASC scores were origi-
nally developed and validated for ischemic stroke risk pre-
diction in nonvalvular AF patients.13,14 Because many of the
components of the CHA2DS2-VASC score coincide with
known risk factors for adverse prognosis in patients with
PCI, it is only reasonable to deduce and attempt expanding
their use farther.
The role of CHA2DS2-VASC scores in predicting car-
diovascular events was previously demonstrated in
 Coronary Artery Disease/CHA2DS2-VASC Score in Patients with PCI
patients without AF with high cardiovascular risk15 and
CHF.16 As for patients with coronary artery disease, the
CHA2DS2-VASC score has been recently evaluated as a
risk stratication tool for major adverse cardiac event
(including all-cause death, MI, destabilizing symptoms
leading to hospitalization, and nonfatal stroke) after PCI
in 1,330 patients without AF and was shown to have
modest discrimination.17 In our study, we have extended
these previous observations to 12,785 patients with PCI
and shown better discrimination for all cause death and
MI. Because the purpose of our study was to evaluate the
outcome of all patients with PCI, regardless of their AF
background, we chose hard clinical end points such as
death and/or nonfatal MI.
Numerous risk stratication models have been developed
to assess short-, medium-, and long-term prognosis after
PCI based on anatomic and clinical factors.3e7 Because
these models were instituted on different patient pop-
ulations, outcome measures, and time periods, they are not
comparable and consequently there is no current recom-
mendation to use one model over the other.18 Furthermore,
some of the scores are complex to calculate, require com-
puter assistance, and are time consuming and thus are less
applied in daily practice. As we demonstrated, we were able
to calculate the simple ACEF score for only 61% of the
cohort. This illustrates one inherent problem with this score
as ejection fraction is not always available at the time of the
PCI especially for elective patients. Conversely, the
CHA2DS2-VASC scores are already widely used in the
context of AF and risk for stroke because it is very easy to
remember and simple to apply at bed side. Our study
objective was not to compare the CHA2DS2-VASC score to
the current available risk scores, nor to validate it against
them. However, we showed the predictive value of the
CHA2DS2-VASC score to be good and even better than the
well-known ACEF score.
Many of the CHA2DS2-VASC score variables (i.e., age,
female gender, diabetes, heart failure) are already well
recognized as outcome predictors after PCI and have been
comprehensively validated.4e7,19 Conversely, the
CHA2DS2-VASC score does not include some other well-
recognized clinical and angiographic predictors.3e7 For
example, kidney injury is a strong outcome predictor in
most of the settings of cardiovascular disease patients.20e24
Yet, we have successfully shown a strong association be-
tween higher CHA2DS2-VASC score and worse outcome.
As for patients with MI and ACS, there are separate risk
stratication models which mainly rely on clinical variables
at presentation.25,26 The linear correlation between a higher
CHA2DS2-VASc score and worse outcome was maintained
for patients with acute MI and ACS as it was for patients
with stable and elective PCI.
Our study has several limitations. First, this is a retro-
spective study from a single center with a mixed population
of patients; however, the study cohort is relatively large and
it represents the real-world daily practice. Furthermore,
similar results were obtained for patients with stable and
ACS. Second, our registry is based on patients who un-
derwent PCI only; therefore, a comparative analysis against
patients who underwent coronary artery bypass surgery
could not have been conducted.
1437
Disclosures
The authors have no conicts of interest to disclose.
Supplementary Data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.
amjcard.2016.02.010.
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