The SYNTAX Trial at 3 Years:
A Global Risk Approach to Identify Patients With 3-Vessel and/or Left Main
Stem Disease Who Could Safely and Efficaciously Be Treated With
Percutaneous Coronary Intervention
Supplementary Appendix
Contents
I.
Flow chart of patients from the SYNTAX trial demonstrating availability
of data
Figure 1: Flow chart.
II.
Supplementary Methods
a. Definitions of Risk Scores
b. Additional Reclassification Methodology with illustrative figures
(Figures 2-3)
III.
Additional Analyses for the Randomised SYNTAX Population
a. Outcomes by tertiles of the SYNTAX Score
Figure 4: Outcomes By Tertile of Risk of the SXscore in isolation within
the Randomised LMS and 3VD PCI Population
b. Outcomes for the Global Risk for the endpoint of Death and MACCE
in the randomised SYNTAX population
Figure 5: Kaplan Meier curves for cumulative rates of Death and
MACCE in the Global Randomised SYNTAX Population.
Figure 6: Comparison of different risk models for Death and MACCE,
utilising calibration (Hosmer-Lemeshow), discrimination (c-statistic) and
1
overall model performances (Brier score) in the Global Randomised
SYNTAX Population.
Tables 1-3: Comparisons (CABG and PCI) of low Global Risk Groups
(GRCLOW) in the Global, LMS and 3VD Randomised SYNTAX
Populations.
c. Outcomes for the Global Risk for the endpoint Death/MI/Stroke in the
Randomised SYNTAX population
Figure 7: Kaplan Meier curves for cumulative rates of Death/MI/Stroke
in the Randomised LMS population
Figure 8: Kaplan Meier curves for cumulative rates of Death/MI/Stroke
in the Randomised LMS population
IV.
Additional Comparative Analyses for the GRCINT and GRCHIGH groups
in the Randomised SYNTAX Populations
Tables 4-6: Comparisons (CABG and PCI) for the intermediate Global
Risk Groups (GRCINT)
Tables 7-9: Comparisons (CABG and PCI) for the high Global Risk
Groups (GRCHIGH)
V.
Reclassification Analyses for Randomised SYNTAX Population
Tables 10-11: Reclassification Analyses
VI.
Additional Analyses for the ‘All-Comers’ SYNTAX Population
Figure 9: Kaplan Meier curves for cumulative rates of Death and
MACCE in the Global ‘All-Comers’ SYNTAX Population.
Figures 10-11: Comparison of different risk models for Death and
MACCE, utilising calibration (Hosmer-Lemeshow), discrimination (c-
2
statistic) and overall model performances (Brier score) in the Global ‘AllComers’ SYNTAX Population.
Tables 12-14: Comparisons (CABG and PCI) of low Global Risk Groups
(GRCLOW) in the Global, LMS and 3VD ‘All-Comers’ SYNTAX
Populations.
VII.
Reclassification Analyses for “All-Comers’ SYNTAX Population
Tables 15-16: Reclassification Analyses
VIII. Additional Material:
Figure 12: Vessel Distribution in the LMS Population According to
SYNTAX Score Tertiles.
IX.
Additional References
3
I.
Flow chart of patients from the SYNTAX trial demonstrating availability
of data .
Based on the original study protocol (1,29) 649 of the 1077 CABG nested registry
patients were randomly allocated for follow up; data from 37 patients were
unavailable (11 patients at baseline and a further 26 patients at follow up).
Figure 1. Flow chart.
4
II.
Supplementary Methods
a) Definitions of Risk Scores
SYNTAX Score (1-4)
The SYNTAX Score Algorithm. (http://www.syntaxscore.com)
The following algorithm is applied to each individual coronary lesion that has a
diameter stenosis greater than 50% and located in a vessel that is larger than 1.5 mm
in diameter – the individual lesion scores are added together to give the final
SYNTAX score.
The Syntax Score Algorithm
1. Arterial dominance
2. Arterial segments involved per lesion
Lesion characteristics
3. Total occlusion
i. Number of segments involved
ii. Age of the total occlusion (>3 months)
iii. Blunt stump
iv. Bridging collaterals
v. First segment beyond the occlusion visible by antegrade or retrograde filling
vi. Side branch involvement
4. Trifurcation
i. Number of segments diseased
5. Bifurcation
i. Medina type
ii. Angulation between the distal main vessel and the side branch <70°
6. Aorto-ostial lesion
7. Severe tortuosity
8. Length >20 mm
9. Heavy calcification
10. Thrombus
11. Diffuse disease/small vessels
i. Number of segments with diffuse disease/small vessels
5
ACEF Score (5-7)
The ACEF score is calculated using the formula:
ACEF= [Age/Ejection fraction (%)] + [1 (if creatinine >2mg/dl)].
The left ventricular ejection fraction (LVEF) is the value recorded prior to the index
PCI procedure, and in the event of multiple available values, the lowest recorded
figure. The serum creatinine value is the value recorded prior to the index PCI.
Clinical SYNTAX score (8)
The Clinical SYNTAX Score is calculated using the formula: Clinical SYNTAX
Score = [SXscore] x [modified ACEF score]. The modified ACEF score is calculated
using the formula: age/ejection fraction+1 point for every 10ml/min reduction in
creatinine clearance below 60ml/min/1.73m2 (up to a maximum of 6 points). The
LVEF is the value recorded prior to the index PCI and in the event of multiple
available values the lowest recorded figure. Creatinine clearance is calculated using
the Cockcroft-Gault equation using the patient’s age, weight, and serum creatinine
values recorded prior to the index PCI. (9)
Additive EuroSCORE (10)
The additive EuroSCORE is calculated by summation of the individual scores from
17 different clinical variables.
Additive EuroSCORE
Patient Factors
Age
Sex
Chronic pulmonary disease
Peripheral arteriopathy
Neurological dysfunction
Previous cardiac surgery
Serum creatinine
Per 5 years or part thereof over the age of 60 years
Female
Long-term use of bronchodilators or steroids for respiratory
disease
Claudication/carotid stenosis >50%/Previous or planned
intervention on the abdominal aorta, limb arteries, or
carotids
Severely affected mobility or day-to-day function
Previous opening of the pericardium
Pre-operatively >200 µmol/l
6
1
1
1
2
2
3
2
Active endocarditis
Critical pre-operative state
Cardiac factors
Unstable angina
Left ventricular function
Recent MI
Pulmonary hypertension
Operative factors
Emergency Operation
Other than isolated CABG
Surgery on thoracic aorta
Post-infarct septal rupture
Antibiotic therapy at time of surgery
Pre-operative cardiac arrest, ventilation, renal failure,
inotropic support, intra-aortic balloon pump use, ventricular
arrhythmia
3
3
Rest pain requiring IV nitrates
Moderate (30%–50%)
Poor (<30%)
Within 90 days
Systolic pulmonary artery pressure >60 mm Hg
2
1
3
2
2
Performed before the start of next working day
Major cardiac procedure other than or in addition to CABG
2
2
3
4
Logistic EuroSCORE (11)
The logistic EuroSCORE utilises the EuroSCORE logistic regression equation and
uses the same risk factors as the additive EuroSCORE.
b) Additional Reclassification Methodology
The SXscore and additive EuroSCORE consists of 3 categories of level of anatomical
disease complexity (2-4) and clinical risk (10,11) respectively. By combining the two
categorical based scores to form the Global Risk (GRC) 9 different risk groups were
created. Based on the principle that comparable clinical outcomes, in patients with a
low SXscore undergoing CABG or PCI, were evident at 3 years (1,12) it was
hypothesised that patients without a high EuroSCORE and/or high SXscore would be
a lower risk population (GRCLOW) population, who would be equally amenable to
CABG or PCI in terms of efficacy and safety.
7
The underlying principles of the reclassification analyses were therefore to ensure that
– in the higher anatomical risk patients (i.e. with intermediate SXscores and lowintermediate EuroSCORE) reclassified as low Global Risk (GRCLOW) – comparability
(or more favourable PCI outcomes) in clinical outcomes between CABG and PCI
would be maintained in this reclassified group. Conversely – in the lower anatomical
risk patients with a high clinical comorbidity (i.e. low SXscore with a high
EuroSCORE) reclassified as a higher Global Risk (GRCINT) – more favourable
surgical clinical outcomes would be evident in this reclassified group.
If reclassification analyses were not undertaken the main danger would be that higher
(or lower risk) patients would be inappropriately reclassified to lower (or higher) risk
groups. This may subsequently not be clinically apparent as the expected lower (or
higher) clinical outcomes within the population the reclassified patients entered,
would potentially dilute the clinical outcomes within the reclassified patients.
Consequently, comparisons of clinical outcomes (between CABG and PCI) within the
reclassified groups are required to ensure that the patients have been appropriately
reclassified. Illustrative figures explaining these concepts are detailed below (Figures
1-2).
8
Figure 2: Comparability (or more favourable PCI outcomes) in Death and MACCE
between CABG and PCI for the higher risk group (intermediate SXscore and lowintermediate EuroSCOREs) reclassified to a lower risk (GRCLOW) group would be
expected.
Figure 3: More favourable clinical outcomes (Death or MACCE) would be expected
with CABG compared to PCI, for the lower risk group (low SXscore and high
EuroSCORE) reclassified to a higher (GRCINT) risk group. This is in keeping with
previous findings of a high EuroSCORE to be an independent predictor of in-hospital
mortality and MACCE after PCI. (13-16)
9
III
Additional Analyses for the Randomised SYNTAX Population
a. Outcomes by tertiles of the SYNTAX Score
Figure 4
At 36-months within both the LMS and 3VD PCI cohorts, a low SXscore group could
not be differentiated from the higher risk groups (low-intermediate SXscore) for
Death and MACCE. Within the LMS PCI population a high SXscore group could
only be differentiated from the lower SXscore groups (low to intermediate SXscore)
for Death and MACCE.
Title: Outcomes By Tertile of Risk of the SXscore in isolation within the Randomised
LMS and 3VD PCI Population
Caption: Kaplan Meier curves for cumulative rate of Death (upper) and MACCE
(lower) at 3-year follow-up, stratified to tertile of the SXscore, event rate ±1.5 SE.
SXscore: LMS Death - PCI
SXscore: 3VD Death- PCI
SXscore: LMS MACCE - PCI
SXscore: 3VD MACCE - PCI
10
b. Outcomes for the Global Risk for the endpoint of Death and MACCE in the
randomised SYNTAX population
Figure 5: Kaplan Meier curves for cumulative rates of Death (upper), and MACCE
(lower) in the Global Randomised SYNTAX population at 3-year follow-up stratified
according to the group of Global Risk, event rate ±1.5 SE.
RANDOMISED DEATH - PCI
RANDOMISED DEATH - CABG
RANDOMISED MACCE - PCI
RANDOMISED MACCE - CABG
11
Figure 6: Comparison of different risk models for the Global Randomised SYNTAX
population for Death (left) and MACCE (right), utilising calibration (HosmerLemeshow), discrimination (c-statistic) and overall model performances (Brier score).
(17)
GLOBAL RANDOMISED SYNTAX
POPULATION – 3-YEAR DEATH
GLOBAL RANDOMISED SYNTAX
POPULATION – 3-YEAR MACCE
12
Tables 1-3: Comparisons (CABG and PCI) of low Global Risk Groups (GRCLOW)
Table 1
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing low Global Risk groups (GRCLOW) for the Global Randomised
PCI and Global Randomised CABG population (N=921).
Event
3 Year
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Cerebrovascular Event
(Stroke), Any
MI, Any
Revascularisation, Any
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft Occlusion
CABG
(N=443)
PCI
(N=478)
Hazard Ratio
[95% CI]
Difference
p-Value
20.4% (86)
11.2% (47)
6.0% (25)
21.6% (102)
8.5% (40)
4.2% (20)
1.06 [0.80, 1.41]
0.74 [0.49, 1.14]
0.70 [0.39, 1.26]
1.2%
-2.7%
-1.8%
0.69
0.17
0.24
3.1% (13)
1.1% (5)
0.34 [0.12, 0.95]
-2.0%
0.031
3.1% (13)
12.0% (49)
11.3% (46)
1.2% (5)
4.9% (23)
16.5% (77)
14.2% (66)
3.7% (17)
1.58 [0.80, 3.12]
1.43 [1.00, 2.04]
1.30 [0.89, 1.89]
3.04 [1.12, 8.23]
1.8%
4.6%
2.9%
2.5%
0.18
0.050
0.17
0.02
3.9% (16)
3.9% (18)
0.99 [0.51, 1.95]
0.0%
0.99
Table 2
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing GRCLOW for the Global Randomised LMS population (N=318).
CABG
(N=152)
PCI
(N=166)
Hazard Ratio
[95% CI]
Difference
p-Value
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Stroke, Any
MI, Any
Revascularisation, Any
23.1% (34)
12.3% (18)
7.5% (11)
3.5% (5)
1.4% (2)
14.6% (21)
15.8% (26)
5.5% (9)
1.2% (2)
0.6% (1)
3.7% (6)
12.8% (21)
0.64 [0.39, 1.07]
0.42 [0.19, 0.94]
0.16 [0.03, 0.70]
0.17 [0.02, 1.46]
2.59 [0.52, 12.82]
0.85 [0.46, 1.56]
-7.3%
-6.8%
-6.3%
-2.9%
2.3%
-1.8%
0.088
0.029
0.0054
0.067
0.23
0.60
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft Occlusion
13.3% (19)
1.3% (2)
10.9% (18)
3.0% (5)
0.81 [0.42, 1.54]
2.20 [0.43, 11.36]
-2.3%
1.7%
0.51
0.33
4.1% (6)
2.5% (4)
0.57 [0.16, 2.01]
-1.6%
0.37
Event
3 Year
13
Table 3
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing GRCLOW for Global Randomised 3VD population (N=603).
CABG
(N=291)
PCI
(N=312)
Hazard Ratio
[95% CI]
Difference
p-Value
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Stroke, Any
MI, Any
Revascularisation, Any
19.0% (52)
10.6% (29)
5.2% (14)
2.9% (8)
4.0% (11)
10.5% (28)
24.7% (76)
10.0% (31)
5.8% (18)
1.3% (4)
5.6% (17)
18.5% (56)
1.35 [0.95, 1.92]
0.95 [0.57, 1.58]
1.14 [0.57, 2.30]
0.45 [0.13, 1.49]
1.40 [0.66, 2.99]
1.88 [1.19, 2.96]
5.7%
-0.5%
0.7%
-1.6%
1.6%
8.0%
0.10
0.85
0.71
0.18
0.38
0.0055
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft Occlusion
10.2% (27)
1.1% (3)
15.9% (48)
4.0% (12)
1.66 [1.04, 2.66]
3.60 [1.02, 12.75]
5.7%
2.9%
0.033
0.034
3.7% (10)
4.6% (14)
1.25 [0.56, 2.81]
0.9%
0.59
Event
3 Year
14
c. Outcomes for the Global Risk for the endpoint Death/MI/Stroke in the
Randomised SYNTAX population
Figure 7: Kaplan Meier curves for cumulative rates of Death/MI/Stroke in the
Randomised LMS SYNTAX population at 3-year follow-up stratified according to
the group of Global Risk, event rate ±1.5 SE.
RANDOMISED DEATH/MI/STROKE - PCI
RANDOMISED DEATH/MI/STROKE - CABG
Figure 8: Kaplan Meier curves for cumulative rates of Death/MI/Stroke in the
Randomised 3VD SYNTAX population at 3-year follow-up stratified according to the
group of Global Risk, event rate ±1.5 SE.
RANDOMISED DEATH/MI/STROKE - PCI
RANDOMISED DEATH/MI/STROKE - CABG
15
IV. Additional Comparative Analyses (CABG and PCI) for the GRCINT &
GRCHIGH groups in the Global, LMS & 3VD Randomised SYNTAX Populations
Tables 4-6: Comparisons (CABG & PCI) for the GRCINT Groups
Table 4
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing GRCINT for the Global Randomised PCI and Global
Randomised CABG patients (N=687)
Event
3 Year
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Cerebrovascular Event
(Stroke), Any
MI, Any
Revascularization, Any
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft
Occlusion
Difference
Relative
%
Change
p-Value1
2.06 [1.51, 2.80]
16.1%
88.2%
<.0001
19.6% (64)
12.3% (40)
1.95 [1.30, 2.94]
2.57 [1.46, 4.53]
9.2%
7.4%
88.9%
148.9%
0.0010
0.0007
2.7% (9)
3.0% (9)
1.09 [0.43, 2.75]
0.3%
11.7%
0.8515
4.3% (15)
10.7% (36)
9.6% (31)
22.7% (72)
2.26 [1.22, 4.19]
2.32 [1.56, 3.47]
5.4%
12.1%
125.7%
112.8%
0.0076
<.0001
9.0% (30)
1.7% (6)
18.3% (58)
6.1% (19)
2.24 [1.44, 3.48]
3.48 [1.39, 8.71]
9.3%
4.4%
103.4%
259.6%
0.0002
0.0045
3.1% (10)
4.6% (15)
1.62 [0.73, 3.62]
1.6%
50.8%
0.2304
CABG
(N=357)
TAXUS
(N=330)
Hazard Ratio
[95% CI]
18.2% (63)
34.3% (112)
10.4% (36)
4.9% (17)
16
Table 5
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing GRCINT for the Randomised LMS population (N=290).
Event
3 Year
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Cerebrovascular Event
(Stroke), Any
MI, Any
Revascularization, Any
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft
Occlusion
Difference
Relative
%
Change
p-Value1
2.00 [1.26, 3.19]
1.49 [0.81, 2.75]
16.4%
5.7%
84.9%
46.8%
0.0028
0.1959
11.0% (16)
1.96 [0.84, 4.59]
5.2%
91.2%
0.1123
2.2% (3)
0.7% (1)
0.33 [0.03, 3.14]
-1.5%
-66.9%
0.3076
6.3% (9)
11.7% (16)
8.9% (12)
11.1% (16)
27.4% (39)
21.0% (30)
1.73 [0.76, 3.91]
2.57 [1.44, 4.60]
2.65 [1.36, 5.18]
4.7%
15.7%
12.1%
74.3%
133.8%
135.4%
0.1837
0.0010
0.0030
2.8% (4)
9.4% (13)
3.22 [1.05, 9.86]
6.6%
232.6%
0.0307
4.5% (6)
6.9% (10)
1.63 [0.59, 4.49]
2.5%
55.4%
0.3394
CABG
(N=143)
TAXUS
(N=147)
Hazard Ratio
[95% CI]
19.3% (27)
12.1% (17)
35.6% (52)
17.8% (26)
5.7% (8)
Table 6
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing GRCINT for the Randomised 3VD population (N=397).
Event
3 Year
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Cerebrovascular Event
(Stroke), Any
MI, Any
Revascularization, Any
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft
Occlusion
Difference
Relative
%
Change
p-Value1
2.08 [1.38, 3.15]
2.39 [1.38, 4.14]
3.14 [1.46, 6.75]
15.7%
11.8%
9.0%
89.3%
127.8%
203.9%
0.0004
0.0014
0.0020
4.9% (8)
1.58 [0.55, 4.54]
1.9%
61.1%
0.3959
2.9% (6)
10.0% (20)
9.1% (18)
0.9% (2)
8.4% (15)
18.9% (33)
16.2% (28)
3.4% (6)
2.98 [1.16, 7.68]
2.06 [1.18, 3.59]
1.92 [1.06, 3.47]
3.54 [0.72, 17.56]
5.6%
8.9%
7.1%
2.5%
194.4%
89.1%
77.8%
260.3%
0.0175
0.0092
0.0280
0.0980
2.1% (4)
2.8% (5)
1.46 [0.39, 5.43]
0.6%
29.9%
0.5716
CABG
(N=214)
TAXUS
(N=183)
Hazard Ratio
[95% CI]
17.6% (36)
9.2% (19)
4.4% (9)
33.3% (60)
21.1% (38)
13.4% (24)
3.0% (6)
17
Tables 7-9: Comparisons (CABG and PCI) for the GRCHIGH Groups
Table 7
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing GRCHIGH for the Global Randomised PCI and Global
Randomised CABG patients (N=181).
Event
3 Year
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Cerebrovascular Event
(Stroke), Any
MI, Any
Revascularization, Any
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft
Occlusion
Difference
Relative
%
Change
p-Value1
1.56 [0.92, 2.63]
1.05 [0.57, 1.92]
1.09 [0.54, 2.18]
11.2%
0.5%
0.6%
40.9%
2.1%
3.1%
0.0973
0.8796
0.8095
3.8% (3)
0.47 [0.12, 1.89]
-3.4%
-47.0%
0.2780
3.4% (3)
3.9% (3)
3.9% (3)
9.5% (8)
25.5% (21)
22.1% (18)
2.64 [0.70, 9.95]
7.35 [2.19, 24.63]
6.19 [1.82, 21.01]
6.1%
21.5%
18.2%
179.2%
548.4%
463.7%
0.1358
0.0001
0.0008
0.0% (0)
3.6% (3)
NA [NA, NA]
3.6%
NA
0.0845
0.0% (0)
3.5% (3)
NA [NA, NA]
3.5%
NA
0.0895
CABG
(N=90)
TAXUS
(N=91)
Hazard Ratio
[95% CI]
27.4% (23)
23.8% (20)
18.2% (15)
38.7% (35)
24.3% (22)
18.8% (17)
7.2% (6)
Table 8
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing GRCHIGH for the Randomised LMS population (N=93).
Event
3 Year
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Cerebrovascular Event
(Stroke), Any
MI, Any
Revascularization, Any
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft
Occlusion
Difference
Relative
%
Change
p-Value1
1.46 [0.72, 2.97]
10.6%
36.6%
0.2880
25.6% (11)
18.6% (8)
0.94 [0.42, 2.10]
1.05 [0.41, 2.72]
-1.3%
-0.3%
-4.7%
-1.5%
0.8859
0.9193
10.6% (5)
5.4% (2)
0.45 [0.09, 2.34]
-5.2%
-49.2%
0.3315
6.0% (3)
5.7% (2)
-0.3%
-4.8%
0.7773
2.3% (1)
24.3% (9)
22.1%
970.9%
0.0031
2.3% (1)
21.7% (8)
19.4%
853.4%
0.0069
0.0% (0)
2.6% (1)
0.77 [0.13, 4.61]
11.67 [1.48,
92.11]
10.13 [1.27,
81.01]
NA [NA, NA]
2.6%
NA
0.2712
0.0% (0)
0.0% (0)
NA [NA, NA]
0.0%
NA
Undef
CABG
(N=50)
TAXUS
(N=43)
Hazard Ratio
[95% CI]
28.9% (14)
39.5% (17)
26.8% (13)
18.9% (9)
18
Table 9
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing GRCHIGH for the Randomised 3VD population (N=88).
Event
3 Year
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Cerebrovascular Event
(Stroke), Any
MI, Any
Revascularization, Any
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft
Occlusion
Difference
Relative
%
Change
p-Value1
1.71 [0.77, 3.80]
1.28 [0.49, 3.29]
1.16 [0.41, 3.26]
12.4%
3.4%
1.9%
49.0%
17.0%
11.3%
0.1850
0.6146
0.7772
2.3% (1)
0.76 [0.05, 12.20]
-0.5%
-16.3%
0.8480
0.0% (0)
6.0% (2)
6.0% (2)
12.7% (6)
26.1% (12)
22.2% (10)
NA [NA, NA]
4.87 [1.09, 21.76]
4.01 [0.88, 18.30]
12.7%
20.1%
16.2%
NA
332.2%
268.1%
0.0253
0.0217
0.0525
0.0% (0)
4.4% (2)
NA [NA, NA]
4.4%
NA
0.2090
0.0% (0)
6.3% (3)
NA [NA, NA]
6.3%
NA
0.1341
CABG
(N=40)
TAXUS
(N=48)
Hazard Ratio
[95% CI]
25.4% (9)
19.8% (7)
17.1% (6)
37.9% (18)
23.2% (11)
19.0% (9)
2.8% (1)
19
V. Reclassification Analyses for Randomised SYNTAX Population
Tables 10-11: Reclassification Analyses
Table 10
Reclassification analyses (intermediate SXscore and low-intermediate EuroSCORE
reclassified to GRCLOW) within the randomised SYNTAX Population: Kaplan-Meier
event rates in reclassified PCI and CABG patients are shown.
Reclassified SYNTAX
Population
Randomised
Randomised LMS
Randomised 3VD
Outcome
Event Rates/Total
Reclassified
CABG Patients
Event Rates/Total
Reclassified
PCI Patients
3-Year MACCE
3-Year death
3-Year MACCE
3-Year Death
3-Year MACCE
3-Year Death
18.7% (39/222)
6.4% (13/222)
24.4% (16/68)
10.8% (7/68)
16.1% (23/154)
4.3% (6/154)
23.0% (55/242)
5.4% (13/242)
15.6% (12/77)
1.3% (1/77)
26.4% (43/165)
7.4% (12/165)
Table 11
Reclassification analyses (low SXscore and high EuroSCORE reclassified to GRC INT)
within the randomised SYNTAX Population: Kaplan-Meier event rates in the
reclassified CABG and PCI patients are shown.
Reclassified SYNTAX
Population
Randomised
Randomised LMS
Randomised 3VD
Outcome
Event Rates/Total
Reclassified
CABG Patients
Event Rates/Total
Reclassified
PCI Patients
3-Year MACCE
3-Year Death
3-Year MACCE
3-Year Death
3-Year MACCE
3-Year Death
24.8% (12/53)
10.1% (5/53)
28.6% (5/19)
11.1% (2/19)
22.5% (7/34)
9.6% (3/34)
32.1% (20/63)
14.5% (9/63)
24.1% (7/29)
6.9% (2/29)
39.1% (13/34)
21.3% (7/34)
20
VI.
Additional Analyses for the All-Comers (Entire Population and
LMS/3VD Cohorts) SYNTAX Population
Figure 9: Kaplan Meier curves for cumulative rate of Death (upper), and MACCE
(lower) in the Global ‘All-Comers’ SYNTAX population at 3-year follow-up
stratified according to the group of Global Risk, event rate ±1.5 SE.
‘ALL-COMERS’ DEATH - PCI
‘ALL-COMERS’ DEATH - CABG
‘ALL-COMERS’ MACCE - PCI
‘ALL-COMERS’ MACCE - CABG
21
Figure 10
Comparison of different risk models for the Global ‘All-Comers’ SYNTAX
population Death (left) and MACCE (right), utilising calibration (Hosmer-Lemeshow
test), discrimination (c-statistic) and overall model performances (Brier score). Renal
function was not collected in all nested registry patients, consequently the ACEF
based scores were excluded from the analysis below.
ALL-COMERS SYNTAX POPULATION
– 3-YEAR MACCE
ALL-COMERS SYNTAX POPULATION
– 3-YEAR DEATH
22
Figure 11
Comparison of different risk models for the ‘All-Comers’ LMS and 3VD populations
for Death (upper) and MACCE (lower) at 3-Years. A smaller Brier score (x-axis) and
larger c-statistic (y-axis) represents a better predictive ability of the risk model.(17)
Yellow arrows represent the incremental predictive benefit of the GRC compared to
the SXscore and additive EuroSCORE within the LMS PCI population, not evident
within the 3VD PCI population with comparability of the GRC and additive
EuroSCORE.
Striped circles represents calibrated additive EuroSCORE and non-calibrated logistic
EuroSCORE in the LMS CABG (MACCE) population and calibrated additive EuroSCORE
and non-calibrated GRC within the 3VD CABG (MACCE) population.
The renal function was not collected in all nested registry patients, consequently the
ACEF based scores were excluded from the analysis below.
23
‘ALL-COMERS’ LMS and 3VD Cohorts: 3-Year Death
3VD Cohort
LMS Cohort
‘ALL-COMERS’ LMS and 3VD Cohorts: 3-Year MACCE
LMS Cohort
3VD Cohort
24
Tables 12-14: Comparisons (CABG and PCI) of low Global Risk Groups (GRCLOW)
Table 12
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, all low Global Risk groups (GRCLOW) for ‘All-Comers’ CABG and ‘AllComers’ PCI patients (N=1156)
Event
3 Year
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Cerebrovascular Event
(Stroke), Any
MI, Any
Revascularisation, Any
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft Occlusion
CABG
(N=626)
PCI
(N=530)
Hazard Ratio
[95% CI]
Difference
pValue
18.0% (108)
10.3% (62)
5.2% (31)
22.3% (117)
8.8% (46)
4.8% (25)
1.28 [0.98, 1.66]
0.84 [0.57, 1.23]
0.92 [0.54, 1.56]
4.4%
-1.5%
-0.4%
0.067
0.38
0.76
3.5% (21)
1.2% (6)
0.32 [0.13, 0.80]
-2.4%
0.01
2.8% (17)
4.8% (25)
1.70 [0.92, 3.15]
2.0%
0.088
9.7% (57)
9.2% (54)
0.8% (5)
17.2% (89)
14.7% (76)
3.7% (19)
1.87 [1.34, 2.61]
1.67 [1.18, 2.37]
4.41 [1.65, 11.82]
7.5%
5.5%
2.9%
0.0002
0.0035
0.0012
3.4% (20)
3.5% (18)
1.03 [0.55, 1.95]
0.1%
0.92
Table 13
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing GRCLOW groups for ‘All-Comers’ LMS CABG and ‘AllComers’ LMS PCI patients (N=419).
Event
3 Year
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Stroke, Any
MI, Any
Revascularisation, Any
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft Occlusion
CABG
(N=234)
PCI
(N=185)
Hazard Ratio
[95% CI]
Difference
pValue
18.0% (41)
18.5% (34)
9.6% (22)
5.3% (12)
4.0% (9)
0.9% (2)
10.7% (24)
9.8% (22)
6.6% (12)
2.7% (5)
0.6% (1)
3.9% (7)
14.8% (27)
12.0% (22)
1.02 [0.65, 1.60]
0.6%
0.94
0.65 [0.32, 1.32]
0.51 [0.18, 1.44]
0.13 [0.02, 1.05]
4.30 [0.89, 20.69]
1.40 [0.81, 2.42]
1.23 [0.68, 2.22]
-3.1%
-2.6%
-3.5%
3.0%
4.1%
2.2%
0.23
0.19
0.025
0.047
0.23
0.49
0.9% (2)
3.8% (7)
4.37 [0.91, 21.02]
3.0%
0.044
4.0% (9)
2.3% (4)
0.54 [0.17, 1.74]
-1.7%
0.29
25
Table 14
Principal effectiveness and safety results, summary of time-to-event analyses intentto-treat, comparing GRCLOW groups for ‘All-Comers’ 3VD PCI and ‘All-Comers’
3VD CABG patients (N=737).
Event
3 Year
Post-Allocation MACCE
Death/Stroke/MI, Any
Death, Any
Stroke, Any
MI, Any
Revascularisation, Any
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft Occlusion
CABG
(N=392)
PCI
(N=345)
Hazard Ratio
[95% CI]
Difference
pValue
17.9% (67)
10.7% (40)
5.1% (19)
3.2% (12)
24.4% (83)
10.0% (34)
5.9% (20)
1.5% (5)
1.42 [1.03, 1.96]
0.93 [0.59, 1.47]
1.16 [0.62, 2.17]
0.46 [0.16, 1.30]
6.4%
-0.7%
0.7%
-1.7%
0.031
0.76
0.65
0.13
4.0% (15)
9.1% (33)
8.8% (32)
0.8% (3)
5.3% (18)
18.5% (62)
16.2% (54)
3.6% (12)
1.34 [0.67, 2.65]
2.20 [1.44, 3.35]
1.96 [1.27, 3.04]
4.45 [1.26, 15.79]
1.3%
9.5%
7.4%
2.8%
0.41
0.0002
0.0021
0.011
3.0% (11)
4.2% (14)
1.41 [0.64, 3.10]
1.2%
0.40
26
VII. Reclassification Analyses for ‘All-Comers’ SYNTAX Population
Tables 15-16: Reclassification Analyses
Table 15
Reclassification analyses (intermediate SXscore and low-intermediate EuroSCORE
reclassified to GRCLOW) within the ‘All-Comers’ SYNTAX Population: KaplanMeier event rates in reclassified PCI and CABG patients are shown.
Reclassified SYNTAX
Population
All-Comers
All-Comers LMS
All-Comers 3VD
Outcome
Event Rates/Total
Reclassified
CABG Patients
Event Rates/Total
Reclassified
PCI Patients
3-Year MACCE
3-Year Death
3-Year MACCE
3-Year Death
3-Year MACCE
3-Year Death
16.7% (56/350)
4.8% (16/350)
18.8% (21/114)
6.3% (7/114)
15.6% (35/236)
4.1% (9/236)
23.3% (62/269)
6.0% (16/269)
19.0% (16/84)
3.6% (3/84)
25.2% (46/185)
7.1% (13/185)
Table 16
Reclassification analyses (low SXscore and high EuroSCORE reclassified to GRC INT)
within the ‘All-Comers’ SYNTAX Population: Kaplan-Meier event rates in
reclassified PCI and CABG patients are shown.
Reclassified SYNTAX
Population
All-Comers
All-Comers LMS
All-Comers 3VD
Outcome
Event Rates/Total
Reclassified
CABG Patients
Event Rates/Total
Reclassified
PCI Patients
3-Year MACCE
3-Year Death
3-Year MACCE
3-Year Death
3-Year MACCE
3-Year Death
21.1% (13/66)
8.1% (5/66)
20.4% (5/26)
8.0% (2/26)
21.4% (8/40)
8.2% (3/40)
30.8% (25/82)
13.6% (11/82)
27.0% (10/37)
10.8% (4/37)
33.9% (15/45)
15.9% (7/45)
27
VIII. Additional Material:
Fig. 12 Vessel Distribution in the LMS Population According to SYNTAX Score
Tertiles.
Upper graphs: proportion of LMS population with isolated LMS disease, or
associated with one (1VD), two (2VD) or three vessel disease (3VD).
Middle graphs: proportion of LMS disease with non distal disease (non distal), distal
bifurcation disease (distal) or both components (both).
Lower graphs: proportion of non-total occlusion and total-occlusion disease within
the coronary tree (not within the LMS).
28
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30