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Usefulness of the CHA2DS2-VASC Score to Predict Adverse

Outcomes in Patients Having Percutaneous Coronary
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 stratification tool for pre-
dicting outcome in clinical applications other than atrial fibrillation 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 significantly 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
significant (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. Ó 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 ¼ 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 (first 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 stratifica-
data was verified with the Israel Central Bureau of Statistics.
tion of patients with PCI, regardless of atrial fibrillation
All data regarding previous and subsequent hospitalizations,
(AF), in a large all-comer PCI cohort.
including all International Classification 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: (þ972) 3-9377108; fax: (þ972) 3-9213221. had at least a score of 1 because all of them underwent PCI,
E-mail address: (K. Orvin). thus, they suffered from vascular atherosclerosis.

0002-9149/16/$ - see front matter Ó 2016 Elsevier Inc. All rights reserved.

5% No. The CHA2DS2-VASc score distribution in the entire cohort.4% Balloon angioplasty 4. LV ¼ left ventricle. For the CHA2DS2-VASC score’s predictive discrimination capa- bility.6% 4 6.4% 3. PCI ¼ percutaneous coronary intervention.7% 5.9% 29.1% Hypertension 73.3% CHA2DS2-VASC All-cause All-cause All-cause All-cause Intervention in proximal vessel segment 44.512.6% 33.1% 39.8 Prior coronary bypass 14. Results We assessed the relation between CHA2DS2-VASC score and clinical outcome which included all-cause mortality at A total of 12. 7 15.4% ACS ¼ acute coronary syndrome.0% 2.5% Vascular dis. of coronary artery anomalies Table 2 1 23.4% Single vessel PCI 84. The frequency of the CHA2DS2-VASC score components.9% 11.3% 7.2 years.5% 57. All tests were 2- Figure 1.2% 9 19. Survival tables were constructed using lifetable analysis.12 Statis- tical analyses were performed using IBM SPSS version 20 (IBM Corporation.3% 8 22.2 Men 76. The survival analysis was defined from the day of the index PCI. * MDRD was used for eGFR calculation.6% 39.1434 The American Journal of Cardiology (www.3 Creatinine (mg/dl) 1. and p <0.785) Age (years) 68.5% 51.2% eGFR ( ml/min/1.4% Clinical outcome according to the CHA2DS2-VASC score >2 43.785 patients (mean age 68. eGFR ¼ estimated glomerular filtration 5 10. ST-elevation MI 7.5% 4.0% Stable angina pectoris 39.5% 16. LM ¼ left main.8% rate.1% Table 1 Baseline characteristics Variable Total cohort (n¼12.7% 13.10. mortality or nonfatal myocardial infarction (MI) at 1-and 5- year follow-up as the secondary end points. MI ¼ myocardial infarction. Armonk.2% 2 2. Baseline parameters were compared between groups using the Student t test for continuous variables and the chi-square test for categorical variables.1% score mortality mortalityþ mortality mortalityþ Unprotected LM intervention 2.1% 37.1% 7. MDRD = Modification of Diet in Renal 6 12.2% Diabetes mellitus 43.5  12.1% Moderate/severe LV dysfunction 12.2% 20.2% 27.ajconline.5% 3 3.73m2)* 82.3% 25.1% Prior heart failure 9.6% Clinical Presentation Figure 2. MI or ACS 60.1% 1-year Non-fatal MI 5-years non-fatal MI Drug eluting stent 47.2% 1 1.0% MI ¼ myocardial infarction.8% 17.8% 4.8% 53.4% 45. ¼ vascular disease.1 27.6% Prior atrial fibrillation 10.2% men) were evaluated for CHA2DS2-VASC score at . 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. Survival curves were constructed using the KaplaneMeier proce- dure with log-rank testing of significance. Continuous var- iables were tested with the KolmogoroveSmirnov test and found to have a normal distribution. New York). The tailed.4% Disease.3% Drug eluting balloon 0.8% Prior stroke 5.1% 2. score was calculated on the index (first) PCI.2% 1-year 5-years Bare metal stent 48.05 was considered significant.2% 34.4% 20. 1-and 5-year follow-up as the primary end points and 76.2% Smoker 34.

6%) ejection fraction þ 1 [if serum creatinine was >2. analysis (Supplementary Figure 1).791 patients angiographic features at the index PCI are listed in Table 1. The CHA2DS2-VASC score distribution at the index ACEF score was of 3. clinical.134 (95% CI 2.7 to 0.7%) 483 (6.1%) 5439 (70.2%).001 conferred by each point of the CHA2DS2-VASC score was Stroke 236 (4. with a C-statistic of 0. score were compared between the patients with stable and . We compared the predictive ability of the CHA2DS2- their index PCI. The therefore classified the patients into 9 groups by the per- frequency of the CHA2DS2-VASC score individual com. the proportional risk conferred by each point of the to 9).1%) 0.309 pa.3%) 1865 (24.4%) <0.7 to 0. presented VASC score to the simple and available ACEF score (age/ with acute coronary syndrome (ACS). CHA2DS2-VASC Stable coronary ACS patients P value The CHA2DS2-VASC score predicted all-cause mortality componnts patients (n¼7729) and death or nonfatal MI in a significant (p <0.0 mg/dl]).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. CHF ¼ congestive heart failure. of which 894 (11. the ACEF score was predictive. Patients with increased score had significantly reduced survival (A) and significantly reduced event-free survival from combined end points including death and nonfatal MI (B).4 years (range the change in risk was not incremental although overall the 3.001 (95% CI 0.001 0.729 (60. Most patients.5 months to 10.507 to 1.1%) 1980 (25.76) for mortality and 0.0%) <0. 7.73 Hypertension 3950 (78. C-statistic of 0.85 to 3.61 to 0.584).73 Age 65-74 years 1521 (30.5%) 1606 (20.69 to Age 75 years 1915 (37.001 of 1. centiles of the ACEF score and performed a KaplaneMeier ponents are presented in Figure 2. cause mortality.8%) <0. The median follow-up time was 6.7 (range 1 analysis.9%) 2631 (34. 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. had ST elevation MI. Both the primary and secondary score was predictive. The individual components of the CHA2DS2-VASC compared with a score of 1 at both 1-and 5-year follow-up.72 (95% CI 0. outcomes during follow-up increased linearly with elevated We performed a separate analysis according to the score (Table 2).001) and (n¼5056) linear fashion as shown in Figure 3. The proportional risk Diabetes mellitus 2385 (47.5%). KaplaneMeier survival curves as stratified for CHA2DS2-VASC score for the entire cohort. the score.442). We PCI is presented in Figure 1.001 surements of the predictive power of the score were 0. Patients’ demographic.7  1. We frequent score of 4 obtained in 2.69). Overall. When testing for prediction of all- A previous diagnosis of AF was present in only 1. In the lower percentiles.762 patients (21.2%) 3124 (40. Most of the patients (59.001 (95% CI 0.4%) <0. with a tients (10.6%). The C-index mea- CHF 887 (17.6%) <0.6 years).545 (95% CI 1. and We were able to calculate the ACEF score in 7. the performance of the CHA2DS2-VASC score was maintained (Supplementary Tables 2 and 3). 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. Coronary Artery Disease/CHA2DS2-VASC Score in Patients with PCI 1435 Figure 3.26 In a multivariate Cox adjusted model including CHA2DS2-VASC and the clinical variables not included in ACS ¼ acute coronary syndrome. Using a Cox The mean CHA2DS2-VASC score was 3.65 (95% CI 0.76). (61% of the cohort).2%) <0.75) for death or nonfatal MI. Women 1176 (23.

both stable coronary artery disease and ACS were found to The role of CHA2DS2-VASC scores in predicting car- be well correlated with the score level.14 Because many of the Discussion components of the CHA2DS2-VASC score coincide with This study demonstrated the CHA2DS2-VASC score known risk factors for adverse prognosis in patients with utility as a simple yet powerful tool to aid the prediction of PCI. ACS (Table 3). The CHA2DS2-VASC score predicted all. In contrast to other diovascular events was previously demonstrated in . it is only reasonable to deduce and attempt expanding outcome in patients with PCI. Mortality risk in patients with their use farther.001) and graded manner for patients with both stable may be easily applied in daily practice. Kaplan-Meier survival curves for combined end points of death and nonfatal MI as stratified for CHA2DS2-VASC score in patients with ACS (A) versus stable patients (B).13. the CHA2DS2-VASC cause mortality and death or nonfatal MI in a significant score is a simple and accustomed scoring tool and therefore (p <0. and ACS with a similar trend (Figures 4 and 5).1436 The American Journal of Cardiology (www. The CHADS2 and CHA2DS2-VASC scores were origi- nally developed and validated for ischemic stroke risk pre- diction in nonvalvular AF patients. available PCI risk stratification tools. Figure Figure 4. KaplaneMeier survival curves for all-cause mortality as stratified for CHA2DS2-VASC score in patients with ACS (A) versus stable patients (B).ajconline.

CHA2DS2-VASC score has been recently evaluated as a risk stratification tool for major adverse cardiac event (including all-cause death. Peterson ED.785 patients with PCI and shown better discrimination for all cause death and creatinine.330 patients without AF and was shown to have found. surgery. Swart M.33:3098e3104. Our study artery bypass surgery and percutaneous coronary intervention for in- dividual patients: development and validation of SYNTAX score II. interval estimation.16 As for patients with coronary artery disease.88(1 Suppl):S2eS22. Practice Guidelines. Combined applied in daily practice. Windecker S. Brennan JM. Mack M. Colombo A. fraction (ACEF score) in assessing risk in patients undergoing percu- recognized clinical and angiographic predictors. them. Vaknin-Assa H. Vaduganathan M. Onuma Y. Am J CHA2DS2-VASc score and worse outcome was maintained Cardiol 2012.20e24 8.18 Furthermore. Ho KK. DeLong ER. our registry is based on patients who un. in the online version. the current available risk scores. Numerous risk stratification models have been developed Edwards FH. a comparative analysis against 11. Ischinger T. Singh M. ulations. Serruys PW. Dai D. objective was not to compare the CHA2DS2-VASC score to Lancet 2013. Lip GY. and ejection CHA2DS2-VASC score does not include some other well. Comparison of late (3- at presentation. Hindricks G. Kirchhof P. Anderson RP. Validation of EuroSCORE II in a modern cohort of patients outcome of all patients with PCI. Diletti R. Morice MC. Battler Yet. Kappetein AP. and time periods. Eur J Cardiothorac Surg 2013. and are time consuming and thus are less Dawkins KD. J Am Coll Cardiol 2010. Linke A. Assali A. Hohloser SH. de Vries T. Garcia-Garcia CHA2DS2-VASC scores are already widely used in the HM. Lev EI. diabetes. Fuchs S.e. Van with stable and elective PCI. Shewan CM. MI. puter assistance. we have extended amjcard. Value of age. the Eberli F. Overall C as a measure of discrimination patients who underwent coronary artery bypass surgery in survival analysis: model specific population value and confidence could not have been conducted. these previous observations to 12. the study cohort is relatively large and ropean Association for Cardio-Thoracic Surgery. Filardo G. Morel MA. Participants NR. 961e972. at http://dx.19 Conversely. Rumsfeld JS.398 procedures in the National Cardiovascular Data Registry. nor to validate it against 6.26 The linear correlation between a higher year) registry data outcomes using bare metal versus drug-eluting stents for treating ST-segment elevation acute myocardial infarctions. however. Le Heuzey JY. Goedhart D. PCI especially for elective patients. Gelder IC. Society of Thoracic Surgeons Quality to assess short-. Wykrzykowska JJ. 3. Ann Thorac Surg 2009. Vergouwe Y. there are separate risk 9. Ernst S. Valgimigli M. most of the settings of cardiovascular disease patients. Farooq V. Steyerberg EW. for patients with acute MI and ACS as it was for patients 10. A. Buszman P. Kornowski R. Corti R. Vranckx P. Atar D. Al-Attar N. Bental T.381:639e650. Eur Heart J 2012. we have successfully shown a strong association be. However. patient cohort. De Caterina R. Eur Heart J 2010. Kornowski R. Heldal M. McShane J. some of the scores are complex to calculate. Morel MA. Conversely. and long-term prognosis after Measurement Task Force. De Sutter J. Chieffo A. Roe MT. Mediratta N.360: mendation to use one model over the other. di Mario C. de Vries T.4e7. therefore. Morice MC. Windecker S.2016. destabilizing symptoms Supplementary Data leading to hospitalization. require com. the The authors have no conflicts of interest to disclose. Spertus JA. stratification models which mainly rely on clinical variables Teplitsky I. comprehensively validated. Klauss V. regardless of their AF undergoing cardiac surgery. Serruys PW. Kappetein AP.17 In our study. Holmes DR Jr. as ejection fraction is not always available at the time of the 5.55:1923e1932. Stat Med 2004. Contemporary well-known ACEF score. and nonfatal stroke) after PCI Supplementary data associated with this article can be in 1. Pencina MJ.76:374e380. SYNTAX Investigators. Second.010. The Society of Thoracic Surgeons 2008 PCI based on anatomic and clinical factors. mortality risk prediction for percutaneous coronary intervention: results from 588. Heidbuchel H. outcome measures. N Engl J Med 2009. Rutten FH. Vergouwe Y. Shahian DM. medium-. Vaknin-Assa H. .109:1563e1568. Raber L. age. Dokholyan RS. Because the purpose of our study was to evaluate the Poullis M.23:2109e2123. Rich JB. Many of the CHA2DS2-VASC score variables (i. example. Battler A. Assali A. Savelieva I. derwent PCI only. we showed the predictive value of the Shaw RE. we were able anatomical and clinical factors for the long-term risk stratification of to calculate the simple ACEF score for only 61% of the patients undergoing percutaneous coronary intervention: the Logistic cohort.3e7 Because cardiac surgery risk models: part 1: coronary artery bypass grafting these models were instituted on different patient pop. Shaw M. 2. we chose hard clinical end points such as 688e694. Krone RJ. Serruys PW. Our study has several limitations. Angelini A. O’Brien SM.4:47e56. kidney injury is a strong outcome predictor in Circ Cardiovasc Interv 2011. Kappetein AP.. Ponikowski P. van Geuns RJ. Juni P. European Society of Cardiology (ESC). Brosh D. Pullan M. Dawkins KD. death and/or nonfatal MI. Morice MC. D’Agostino RB. Stahle E.25. Serruys PW. European Heart Rhythm Association. Peterson ED. Alfieri O. Furthermore. van Klaveren D. van Es GA. van Es GA. Klein LW.1016/j. Lev EI. Garcia-Garcia H. Morel recognized as outcome predictors after PCI and have been MA. Meliga E. modest discrimination.3e7 For taneous coronary interventions in the ‘All-Comers’ LEADERS trial. Anatomical context of AF and risk for stroke because it is very easy to and clinical characteristics to guide decision making between coronary remember and simple to apply at bed side. grafting for severe coronary artery disease. Wijns W. this is a retro.doi. CHA2DS2-VASC score to be good and even better than the Brindis RG. Mohr FW. Chalmers J.31: 2369e2429. Rao SV. Camm AJ. spective study from a single center with a mixed population Goette A. heart failure) are already well 7. Prendergast B. Farooq V. As we demonstrated. Onuma Y. Guidelines for the management of atrial fibrilla- similar results were obtained for patients with stable and tion: the Task Force for the management of atrial fibrillation of the ACS. Steyerberg EW. they are not Percutaneous coronary intervention versus coronary-artery bypass comparable and consequently there is no current recom. As for patients with MI and ACS. Schotten U.02. 4. First. This illustrates one inherent problem with this score Clinical SYNTAX score. Fabri B. Colonna P. the Feldman T. Garg S. Catheter Cardiovasc Interv 2010. Eu- of patients. Bental T. Kolh P.43: background. DeLong ER. Coronary Artery Disease/CHA2DS2-VASC Score in Patients with PCI 1437 patients without AF with high cardiovascular risk15 and Disclosures CHF. ESC Committee for it represents the “real-world” daily practice. MI. Weintraub WS. Haan CK. Gorenek B. Ferraris VA. Normand SL. Comparative analysis of major clinical outcomes using drug-eluting stents versus bare-metal stents in a large consecutive tween higher CHA2DS2-VASC score and worse outcome. Brosh D. female gender.

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