Online Appendix
Contents
Page
I. Investigators and Trial Personnel List
2
II. Online Methods Section
A. Inclusion Criteria
4
B. Exclusion Criteria
4
III. Online Tables
A. Online Table 1. Medications
6
B. Online Table 2. Clinical Events in the As-Treated Analysis
8
E. Online Table 3. Clinical Events According to Baseline SYNTAX Score
10
Tertile
IV. Online Figures
A. Online Figure 1. Kaplan-Meier Curves for the Landmark Analyses
13
B. Online Figure 2. Cumulative Incidence of Primary and Secondary End
14
Points according to Baseline SYNTAX Score Tertile
1
I Investigators and Trial Personnel List
The following persons participated in the enrollment of patients, data collection, or study
coordination. Number of patients enrolled per site in the randomized controlled trial and
registries is indicated following the site name in parentheses.
Investigators: SJ Park, JM Ahn, JH Roh, YH Kim, DW Park, SC Yun, SW Lee, CW Lee,
SW Park, Asan Medical Center, Seoul, South Korea; DS Lim and HS Son, Korea University
Anam Hospital, Seoul, South Korea; SW Rha and HJ Kim, Korea University Guro Hospital,
Seoul, South Korea; SG Lee and JP Jung, Ulsan University Hospital, Ulsan, South Korea; HC
Gwon and YT Kim, Samsung Medical Center, Seoul, South Korea; HS Kim and GB Kim,
Seoul National University Hospital, Seoul, South Korea; IH Chae and GH Park, Seoul
National University Hospital, Bundang, South Korea; Y Jang and KJ Yoo, Yonsei University
Severance Hospital, Seoul, South Korea; MH Jeong and BH Ahn, Chonnam National
University Hospital, Gwangju, South Korea; SJ Tahk and SH Lim, Ajou University Medical
Center, Suwon, South Korea; KB Seung and GH Go, Catholic University of Korea, St.
Mary’s Hospital, Seoul, South Korea.
Author Contributions: conception and design — SJ Park, JM Ahn, JH Roh, YH Kim, SC
Yun; analysis and interpretation of data — SJ Park, JM Ahn, JH Roh, YH Kim, SC Yun;
drafting of the manuscript — SJ Park, JM Ahn, JH Roh, YH Kim, SC Yun; critical revision
of the manuscript for important intellectual content — SJ Park, JM Ahn, JH Roh, YH Kim,
DW Park, SC Yun, SW Lee, CW Lee, SW Park, DS Lim, SW Rha, SG Lee, HC Gwon, HS
Kim, IH Chae, Y Jang, MH Jeong, SJ Tahk, KB Seung; final approval of the manuscript —
SJ Park, JM Ahn, JH Roh, YH Kim, DW Park, SC Yun, SW Lee, CW Lee, SW Park, DS
Lim, SW Rha, SG Lee, HC Gwon, HS Kim, IH Chae, Y Jang, MH Jeong, SJ Tahk, KB
2
Seung; statistical expertise — SC Yun, YH Kim, JM Ahn, JH Roh, SJ Park; obtaining of
public funding — SJ Park; administrative, technical, or logistic support — SJ Park, JM Ahn,
JH Roh, YH Kim, DW Park, SC Yun, SW Lee, CW Lee, SW Park; acquisition of data — SJ
Park, JM Ahn, JH Roh, YH Kim, DW Park, SC Yun, SW Lee, CW Lee, SW Park, DS Lim,
SW Rha, SG Lee, HC Gwon, HS Kim, IH Chae, Y Jang, MH Jeong, SJ Tahk, KB Seung.
Data and Safety Monitoring Board: MS Lee (University of Ulsan College of Medicine),
KY Cho (Hallym University Sacred Heart Hospital); JY Yang (National Health Insurance
Corporation Ilsan Hospital); UC Kang (Daejeon University)
Event-Adjudication Committee: JJ Kim (University of Ulsan College of Medicine), JH Oh
(University of Ulsan College of Medicine), SH Kim (University of Ulsan College of
Medicine)
3
II Online Methods Section
Inclusion and Exclusion Criteria
Inclusion Criteria
1. The patient must be at least 18 years of age.
2. The patient must have significant de novo unprotected left main coronary artery
(ULMCA) stenosis (>50% by visual estimation) with or without any additional target
lesions (>70% by visual estimation). “Unprotected” in this context means that no
perfusion distal to the left main stenosis is supplied by either a patent bypass graft or
a collateral vessel.
3. Left main lesions and lesions outside ULMCA (if present) must be potentially
comparably treatable with coronary stenting and coronary artery bypass graft
(CABG).
4. Patients with stable (CCS class 1 to 4) or acute coronary syndromes (unstable angina
pectoris Braunwald class IB, IC, IIB, IIC, IIIB, IIIC or Non-ST elevation myocardial
infarction [MI]) or patients with atypical chest pain or without symptoms but having
documented myocardial ischemia may be enrolled.
5. The patient or guardian must agree to the study protocol and the schedule of clinical
and angiographic follow up, and must provide informed, written consent, as
approved by the appropriate Institutional Review Board/Ethical Committee of the
respective clinical site.
Exclusion Criteria
1. Known hypersensitivity or contraindication to any of the following medications:
4
 Heparin
 Aspirin
 Both clopidogrel and ticlopidine
 Sirolimus
 Stainless steel and/or
 Contrast media (patients with documented sensitivity to contrast which can be
effectively pre medicated with steroids and diphenhydramine [e.g. rash] may be
enrolled. Patients with true anaphylaxis to prior contrast media, however, should
not be enrolled).
2. Systemic (intravenous) sirolimus use within 12 months.
3. Any previous percutaneous coronary intervention (PCI) within 1 year
4. Previous bypass surgery
5. Any previous PCI of a ULMCA or ostial left circumflex artery or ostial left anterior
descending artery lesion within 1 year
6. Intention to treat more than one totally occluded major epicardial vessel
7. Acute MI within 1 week
8. Ejection fraction <30%.
9. Cardiogenic shock
10. Any stroke with a persistent neurological deficit or any cerebrovascular accident
within 6 months
11. Creatinine level ≥ 2.0 mg/dL or dependence on dialysis.
12. Severe hepatic dysfunction (AST and ALT ≥ 3 times upper normal reference
values).
5
13. Gastrointestinal or genitourinary bleeding within the prior 3 months, or major surgery
within 2 months.
14. History of bleeding diathesis or known coagulopathy (including heparin-induced
thrombocytopenia), or will refuse blood transfusions.
15. Current known current platelet count <100,000 cells/mm3 or Hgb <10 g/dL.
16. A planned elective surgical procedure that would necessitate interruption of
thienopyridines during the first 1 year post enrollment.
17. Non-cardiac co-morbid conditions with life expectancy <1 year or that may result in
protocol non-compliance (per site investigator’s medical judgment).
18. Active participation in another drug or device investigational study, which has not
completed the primary end point follow-up period.
19. Unable or unwilling to follow-up with visits required by protocol
20. Female of childbearing potential, unless a recent pregnancy test is negative, who
possibly plan to pregnant any time after enrollment into this study
6
III Online Tables
Online Table 1: Medications at Discharge and Follow-up.
Medication
PCI
CABG
P value
At discharge
295/298 (99.0)
290/294 (98.6)
0.69
1 month after procedure
294/298 (98.7)
288/293 (98.3)
0.72
6 months after randomization
287/296 (97.0)
279/292 (95.5)
0.37
12 months after randomization
277/292 (94.9)
274/291 (94.2)
0.71
5 years after randomization
245/262 (93.5)
231/252 (91.7)
0.42
At discharge
293/298 (98.3)
272/294 (92.5)
0.001
1 month after procedure
293/298 (98.3)
268/293 (91.5)
<0.001
6 months after randomization
283/296 (95.6)
242/292 (82.9)
<0.001
12 months after randomization
255/292 (87.3)
224/291 (77.0)
0.001
5 years after randomization
185/262 (70.6)
136/252 (54.0)
<0.001
At discharge
298/298 (100)
294/294 (100)
NA
1 month after procedure
298/298 (100)
291/293 (99.3)
0.15
6 months after randomization
292/296 (98.6)
283/292 (96.9)
0.15
12 months after randomization
278/292 (95.2)
279/291 (95.9)
0.69
5 years after randomization
254/262 (96.9)
236/252 (93.7)
0.077
At discharge
290/298 (97.3)
268/294 (91.2)
0.001
1 month after procedure
289/298 (97.0)
265/293 (90.4)
0.001
6 months after randomization
278/296 (93.9)
238/292 (81.5)
<0.001
12 months after randomization
254/292 (87.0)
219/291 (75.3)
<0.001
5 years after randomization
176/262 (67.2)
131/252 (52.0)
<0.001
182/298 (61.1)
121/294 (41.2)
<0.001
Aspirin
Clopidogrel
Any antiplatelet drug
Dual antiplatelet drugs
Other medications at discharge
At discharge
Beta-blocker
7
Calcium-channel blocker
184/298 (61.7)
136/294 (46.3)
<0.001
ACE inhibitor
45/298 (15.1)
27/294 (9.2)
0.028
Angiotensin II-receptor antagonist
73/298 (24.5)
53/294 (18.0)
0.055
Statin
215/298 (72.1)
216/294 (73.5)
0.72
Beta-blocker
145/262 (55.3)
111/252 (44.0)
0.01
Calcium-channel blocker
163/262 (62.2)
122/252 (48.4)
0.002
ACE inhibitor
31/262 (11.8)
28/252 (11.1)
0.80
Angiotensin II-receptor antagonist
81/262 (30.9)
72/252 (28.6)
0.56
Statin
130/262 (49.6)
121/252 (48.0)
0.72
5 years after randomization
CABG denotes coronary artery bypass graft; NA, not available; PCI, percutaneous coronary
intervention.
8
Online Table 2: Study outcomes of the as-treated groups at the 5 year follow-up.
Endpoint
PCI
CABG
(N=327)
(N=272)
Hazard ratio (95% CI)
P value
Number (%)*
MACCE
Death from any cause
Cardiac Death
Noncardiac Death
Myocardial Infarction
Q wave MI
Non-Q wave MI
Stroke
Death, MI, or stroke
Repeat revascularization
62 (19.2)
32 (12.0)
1.67 (1.09-2.56)
0.017
21 (6.6)
19 (7.1)
0.92 (0.50-1.72)
0.80
15 (4.8)
16 (6.1)
0.79 (0.39-1.59)
0.50
6 (1.9)
3 (1.2)
1.66 (0.41-6.63)
0.47
5 (1.6)
6 (2.2)
0.69 (0.21-2.26)
0.54
3 (0.9)
4 (1.5)
0.62 (0.14-2.77)
0.53
2 (0.6)
2 (0.8)
0.83 (0.12-5.90)
0.85
3 (1.0)
1 (0.4)
2.49 (0.26-23.92)
0.41
29 (9.0)
24 (9.0)
1.01 (0.59-1.73)
0.98
46 (14.6)
13 (4.9)
3.07 (1.66-5.69)
< 0.001
9
Target vessel revascularization
Ischemia-driven TVR
Clinically driven TVR
Death, MI, or Ischemia-driven TVR
43 (13.7)
11 (4.1)
3.40 (1.76-6.60)
< 0.001
39 (12.4)
10 (3.8)
3.38 (1.69-6.77)
< 0.001
32 (10.2)
10 (3.8)
2.74 (1.34-5.57)
0.004
59 (18.3)
31 (11.6)
1.64 (1.06-2.54)
0.024
*Percentages are Kaplan-Meier estimates from an as-treated analysis. A log-rank test was used to calculate p values. Ischemia-driven TVR
was defined as any repeat revascularization with either PCI or CABG in the treated vessel having at least 50% diameter stenosis in the
presence of ischemic signs or symptoms or at least 70% diameter stenosis in the absence of ischemic signs or symptoms. Clinically driven
TVR excluded lesions without ischemic symptoms or signs from the ischemia-driven TVR. CABG denotes coronary artery bypass grafting;
CI, confidence interval; MACCE, major adverse cardiac or cerebrovascular events; MI, myocardial infarction; PCI, percutaneous coronary
intervention; TVR, target vessel revascularization.
10
Online Table 3: Study outcomes at the 5-year follow-up, according to baseline SYNTAX
score tertile.*
SYNTAX score 0-22
MACCE
Death or stroke or MI
Death
Cardiac death
Noncardiac death
MI
Q wave MI
Non-Q wave MI
Stroke
Repeat revascularization
TVR
Ischemia-driven
TVR
Clinically
driven
TVR
SYNTAX score 23-32
MACCE
Death or stroke or MI
Death
Cardiac death
Noncardiac death
MI
Q wave MI
Non-Q wave MI
Stroke
Repeat revascularization
TVR
Ischemia-driven
TVR
Clinically
driven
TVR
SYNTAX score ≥33
MACCE
Death or stroke or MI
PCI
N=129
16 (12.5)
10 (7.8)
5 (3.9)
4 (3.2)
1 (0.8)
3 (2.4)
2 (1.6)
1 (0.8)
2 (1.6)
13 (10.3)
11 (8.7)
CABG
N=104
13 (13.0)
8 (8.0)
7 (7.0)
5 (5.0)
2 (2.1)
1 (1.1)
0
1 (1.1)
0
8 (8.1)
7 (7.1)
HR (95% CI)
p value
0.98 (0.47-2.05)
0.99 (0.39-2.51)
0.56 (0.18-1.76)
0.63 (0.17-2.33)
0.39 (0.04-4.32)
2.37 (0.25-22.76)
NA
0.79 (0.05-12.56)
NA
1.31 (0.54-3.17)
1.26 (0.49-3.25)
0.97
0.98
0.31
0.48
0.43
0.44
0.21
0.86
0.21
0.54
0.63
9 (7.2)
6 (6.1)
1.20 (0.43-3.37)
0.73
8 (6.4)
6 (6.1)
1.06 (0.37-3.06)
0.91
N=102
22 (21.7)
11 (10.9)
9 (8.9)
4 (4.2)
5 (4.9)
2 (2.0)
1 (1.0)
1 (1.0)
0
13 (13.2)
13 (13.2)
N=97
12 (12.6)
7 (7.4)
6 (6.4)
6 (6.4)
0
0
0
0
1 (1.0)
7 (7.5)
6 (6.4)
1.85 (0.91-3.73)
1.53 (0.59-3.95)
1.45 (0.52-4.08)
0.65 (0.18-2.30)
NA
NA
NA
NA
NA
1.85 (0.74-4.64)
2.16 (0.82-5.69)
0.083
0.38
0.48
0.50
0.029
0.17
0.33
0.33
0.31
0.18
0.11
13 (13.2)
5 (5.3)
2.58 (0.92-7.24)
0.061
10 (10.2)
4 (4.2)
2.47 (0.78-7.88)
0.11
N=58
N=68
14 (24.2)
4 (6.9)
13 (19.2)
10 (14.8)
1.37 (0.64-2.91)
0.47 (0.15-1.51)
0.41
0.20
11
Death
3 (5.2)
9 (13.3)
0.39 (0.11-1.45)
0.14
Cardiac death
3 (5.2)
8 (12.0)
0.44 (0.12-1.66)
0.21
Noncardiac death
0
1 (1.5)
NA
0.36
MI
1 (1.7)
1 (1.5)
1.19 (0.07-19.08)
0.90
Q wave MI
1 (1.7)
1 (1.5)
1.19 (0.07-19.08)
0.90
Non-Q wave MI
0
0
NA
NA
Stroke
0
1 (1.5)
NA
0.35
Repeat revascularization
12 (21.6)
5 (7.5)
2.99 (1.05-8.49)
0.031
TVR
12 (21.7)
4 (6)
3.78 (1.22-11.73)
0.013
Ischemia-driven
11 (19.8)
4 (6.0)
3.44 (1.10-10.81)
0.024
TVR
Clinically
driven
9 (16.2)
4 (6.0)
2.76 (0.85-8.95)
0.078
TVR
*Percentages are Kaplan-Meier estimates from the intention-to-treat analysis. A log-rank test
was used to calculate p values. Ischemia-driven TVR was defined as any repeat
revascularization with either PCI or CABG in the treated vessel having at least 50% diameter
stenosis in the presence of ischemic signs or symptoms or at least 70% diameter stenosis in
the absence of ischemic signs or symptoms. Clinically driven TVR excluded lesions without
ischemic symptoms or signs from the ischemia-driven TVR. CABG denotes coronary artery
bypass grafting; CI, confidence interval; MACCE, major adverse cardiac or cerebrovascular
events; MI, myocardial infarction; NA, not applicable; PCI, percutaneous coronary
intervention; TVR, target vessel revascularization.
12
III Online Figures
Online Figure 1: Kaplan-Meier Curves for the Landmark Analyses. Shown are the
cumulative incidences of major adverse cardiac or cerebrovascular events (A), ischemiadriven target vessel revascularization (B) in the two study groups, stratified on the basis of a
landmark point at 1 year after randomization.
13
Online Figure 2: Kaplan-Meier cumulative event curves at the 5-year follow-up,
according to baseline SYNTAX score tertile.*
14
* Percentages are Kaplan-Meier estimates from the intention-to-treat analysis. P values were
calculated with the use of log-rank test. CABG denotes coronary artery bypass graft; PCI,
percutaneous coronary intervention.
15