1. Long-Term Forecasting and Comparison of Mortality in the Evaluation of the Xience Everolimus-Eluting Stent Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization (EXCEL) Trial: Prospective Validation of the SYNTAX Score II
Carlos M. Campos; David van Klaveren; Vasim Farooq; Charles A. Simonton; Arie-Peter Kappetein; Joseph F. Sabik III; Ewout W Steyerberg; Gregg W. Stone; Patrick W. Serruys; on behalf of the EXCEL Trial Investigators
Wednesday, March 4, 2015
7:00-10:00 am

2. Abbott Confidential. For Internal Use Only
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.

3. SYNTAX Score II Prospective Validation
Although numerous risk scores and prospective trials are available in the medical literature, their performances are reported when the outcomes are already known
The aim of the present study is to apply the SYNTAX score II in the ongoing EXCEL trial, in order to forecast the 4-year mortality outcomes in the PCI and CABG arms, and to describe how clinical characteristics impact on the long term mortality predictions between CABG and PCI
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
Steyerberg EW et al. European Heart Journal (2014) 35, 1925–1931

4. SYNTAX Score II Variables
SYNTAX Score II was developed by applying a Cox proportional hazards model to the results of SYNTAX trial obtaining a combination of clinical and anatomical independent predictors of 4 years all-cause mortality:
ANATOMICAL SYNTAX SCORE LM
AGE
Cr Clearance
LVEF
Gender
PVD
COPD
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
Farooq V et al. Lancet 2013; 381: 639–50

5. SYNTAX Score II EQUIPOISE FOR LONG TERM MORTALITY BETWEEN CABG AND PCI
AGE
CrCl EF
PVD
Diabetes
COPD
3VD
LMS F M
EQUIPOISE FOR LONG TERM MORTALITY BETWEEN CABG AND PCI
Findings that were validated in the multinational DELTA Registry…

6. SYNTAX Score II Case Example 1 CABG PCI Total Points: 30 CABG
4 Year Mortality: 6.8%
PCI
4 Year Mortality: 15.1%
Total Points: 40

8. Results (Examples):
Decision making - between CABG and PCI - guided by the SYNTAX Score II to be endorsed by the Heart Team.

9. Net Reclassification Index=0.5
SYNTAX Score II
Net Reclassification Index=0.5
P<0.01
SSII Improved by 50% the Risk Stratification when compared with Anatomical SYNTAX score
PCI group
CABG group
Anatomical SYNTAX Score
SYNTAX Score II
Observed Mortality
Predicted Mortality
Campos CM et al. Circ J. 2014;78(8):

10. EXCEL trial Enrollment
1905 underwent randomization
Key Inclusion Criteria:
Unprotected left main coronary artery (ULMCA) disease with angiographic diameter stenosis (DS) ≥70%
ULMCA disease with angiographic DS ≥50% but <70% with evidence of ischemia
Left Main Equivalent Disease
SYNTAX score <33
957 assigned to
undergo CABG
948 assigned to
undergo PCI
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
Campos CM et al. EHJ (in press)

11. SYNTAX Score II in EXCEL trial Data Analysis
The individual predicted mortality and the odds ratio (OR) of the two randomized revascularization strategies were calculated using the SYNTAX Score II. To determine the 95% prediction intervals (PI) the trial was simulated 10,000 times and generated 4-year mortality from predictions based on consecutive bootstrap samples
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.

12. SYNTAX Score II in EXCEL trial Data Analysis
Favors PCI
Favors CABG
TRIAL RESULTS SIMULATION
To determine the 95% prediction intervals (PI) the trial was simulated 10,000 times and generated 4-year mortality from predictions based on consecutive bootstrap samples
Campos CM et al. EHJ (in press)

13. EXCEL trial SYNTAX Score II Baseline Variables
PCI
N=948
CABG
N=957
Site Anatomical SYNTAX Score (IQR)
21.0 (15-26)
20.0 ( )
Age, years (IQR)
66.0 ( )
66.0 ( )
Creatinine Clearance, ml/min (IQR)
85.7 ( )
84.6 ( )
LVEF (IQR)
60.0 ( )
60.0 ( )
Left Main Coronary Artery Disease, n (%)
948 (100)
957 (100)
Female gender, n (%)
226 (23.8)
214 (22.4)
COPD, n (%)
67 (7.1)
81 (8.5)
PVD, n (%)
97 (10.3)
84 (8.8)
Campos CM et al Jan 12. pii: ehu518. [Epub ahead of print]

14. 4-year Mortality Simulations Overall Results
Predicted 4-y mortality PCI,%
(95% PI)
8.5
( )
Predicted 4-y mortality CABG,%
10.5
( )
OR PCI:CABG
0.79
( )
Confidence Interval (CI): Asso­ci­ated with observations  and is a fre­quen­tist con­cept
Pre­dic­tion Inter­val (PI): has the same frequentist concept but is asso­ci­ated with a vari­able yet to be observed
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
Campos CM et al Jan 12. pii: ehu518. [Epub ahead of print]

15. 4-year Mortality Simulations Stratified by Anatomical SYNTAX score
Favor CABG: 2.1%
Favor CABG:
4.6%
Neutral: 54.2%
Favor PCI:
43.7%
Neutral:
84.1%
Favor PCI:
11.3%
Predicted 4-y mortality PCI,%
(95% PI)`
7.4
( )
Predicted 4-y mortality CABG,%
(95% PI)
10.3
( )
OR PCI:CABG (95% PI)
0.69
( )
Predicted 4-y mortality PCI,%
(95% PI)`
10.1
( )
Predicted 4-y mortality CABG,%
(95% PI)
10.8
( )
OR PCI:CABG (95% PI)
0.93
( )
PI: prediction interval
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
Campos CM et al Jan 12. pii: ehu518. [Epub ahead of print]

16. 4-year Mortality Simulations Stratified by Age
Age ≤66 years
Age >66 years
Favor PCI:
12.1%
Neutral:
81.1%
Favor CABG:
6.8%
2.4%
41.3%
56.3%
Predicted 4-y mortality PCI,%
(95% PI)`
5.4
( )
Predicted 4-y mortality CABG,%
(95% PI)
5.8
( )
OR PCI:CABG (95% PI)
0.92
( )
Predicted 4-y mortality PCI,%
(95% PI)`
11.8
( )
Predicted 4-y mortality CABG,%
(95% PI)
15.41
( )
OR PCI:CABG (95% PI)
0.73
( )
PI: prediction interval
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
Campos CM et al. EHJ (in press)

17. 4-year Mortality Simulations Stratified by Gender
Female
Male
Favor CABG: 37.0%
Neutral: 61.8%
Favor CABG:
0.8%
Neutral: 35.1%
Favor PCI:
1.2%
Favor PCI:
64.1%
Predicted 4-y mortality PCI,%
(95% PI)`
13.1
( )
Predicted 4-y mortality CABG,%
(95% PI)
8.7
( )
OR PCI:CABG (95% PI)
1.59
( )
Predicted 4-y mortality PCI,%
(95% PI)`
7.1
( )
Predicted 4-y mortality CABG,%
(95% PI)
11.1
( )
OR PCI:CABG (95% PI)
0.61
( )
PI: prediction interval
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
Campos CM et al Jan 12. pii: ehu518. [Epub ahead of print]

18. 4-year Mortality Simulations Stratified by COPD
Without COPD
With COPD
Favor CABG:
7.2%
Favor PCI:
28.5%
Neutral:
64.3%
Favor CABG:
0.7%
30.7%
68.6%
Predicted 4-y mortality PCI,%
(95% PI)`
7.9
( )
Predicted 4-y mortality CABG,%
(95% PI)
9.1
( )
OR PCI:CABG (95% PI)
0.86
( )
Predicted 4-y mortality PCI,%
(95% PI)`
16.7
( )
Predicted 4-y mortality CABG,%
(95% PI)
26.1
( )
OR PCI:CABG (95% PI)
0.57
( )
PI: prediction interval
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
Campos CM et al Jan 12. pii: ehu518. [Epub ahead of print]

19. 4-year Mortality Simulations Stratified by PVD
Without PVD
With PVD
Favor CABG:
3.4%
Favor PCI:
41.2%
Neutral:
55.4%
3.5%
Favor:
17.2%
79.3%
Predicted 4-y mortality PCI,%
(95% PI)`
6.9
( )
Predicted 4-y mortality CABG,%
(95% PI)
9.0
( )
OR PCI:CABG (95% PI)
0.75
( )
Predicted 4-y mortality PCI,%
(95% PI)`
22.5
( )
Predicted 4-y mortality CABG,%
(95% PI)
26.5
( )
OR PCI:CABG (95% PI)
0.82
( )
PI: prediction interval
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
Campos CM et al Jan 12. pii: ehu518. [Epub ahead of print]

20. 4-year Mortality Simulations Stratified by LVEF
Favor CABG:
14.5%
Neutral:
83.7%
Favor CABG:
1.9%
Neutral:
47.4%
Favor PCI:
1.8%
Favor PCI:
50.7%
Predicted 4-y mortality PCI,%
(95% PI)`
18.3
( )
Predicted 4-y mortality CABG,%
(95% PI)
15.1
( )
OR PCI:CABG (95% PI)
1.25
( )
Predicted 4-y mortality PCI,%
(95% PI)`
7.1
( )
Predicted 4-y mortality CABG,%
(95% PI)
9.9
( )
OR PCI:CABG (95% PI)
0.70
( )
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
PI: prediction interval

21. 4-year Mortality Simulations Stratified by CrCl
Creatinine Clearance >85 ml/min
Creatinine Clearance ≤ 85 ml/min
Favor CABG:
2.1%
Favor PCI:
33.5%
5.5%
23.7%
Neutral:
70.8%
Neutral:
64.4%
Predicted 4-y mortality PCI,%
(95% PI)`
12.2
( )
Predicted 4-y mortality CABG,%
(95% PI)
14.0
(8.5-20)
OR PCI:CABG (95% PI)
0.86
( )
Predicted 4-y mortality PCI,%
(95% PI)`
4.9
( )
Predicted 4-y mortality CABG,%
(95% PI)
7.0
( )
OR PCI:CABG (95% PI)
0.68
( )
PI: prediction interval
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
Campos CM et al Jan 12. pii: ehu518. [Epub ahead of print]

22. Conclusions
The prospective use of a decision making and risk prediction tool (SYNTAX Score II) was achievable in a large-scale randomized trial on completion of enrolment of subjects in which the follow-up results are blinded
The SYNTAX Score II predicted a lower 4-year mortality in the PCI arm of the EXCEL trial, with a 40% chance that this will achieve statistical significance compared to the CABG arm
Clinical characteristics had a clear impact on long-term mortality predictions
The accuracy of these mortality predictions will be compared with actual outcome data from EXCEL in the coming years.
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.

23. Abbott Confidential. For Internal Use Only
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.

24. SYNTAX Score II EQUIPOISE FOR LONG TERM MORTALITY BETWEEN CABG AND PCI
AGE
CrCl EF
PVD
Diabetes
COPD
3VD
LMS F M
EQUIPOISE FOR LONG TERM MORTALITY BETWEEN CABG AND PCI
Findings that were validated in the multinational DELTA Registry…

25. 4-year Mortality Simulations Stratified by Diabetes
Favor PCI:
37.5%
Favor CABG:
2.5%
14.2%
3.3%
Non-Diabetics
Diabetics
Neutral:
82.5%
60%
Predicted 4-y mortality PCI,%
(95% PI)`
7.9
( )
Predicted 4-y mortality CABG,%
(95% PI)
10.2
( )
OR PCI:CABG (95% PI)
0.75
( )
Predicted 4-y mortality PCI,%
(95% PI)`
9.9
( )
Predicted 4-y mortality CABG,%
(95% PI)
11.3
( )
OR PCI:CABG (95% PI)
0.86
( )
Abbott Confidential. For Internal Use Only. Not to be reproduced, excerpted or distributed. ©2013 Abbott Laboratories.
PI: prediction interval