JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY

VOL. 65, NO. 20, 2015

2015 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION

PUBLISHED BY ELSEVIER INC.

ISSN 0735-1097/$36.00
[Link]

Randomized Trial of Stents

Versus Bypass Surgery for
Left Main Coronary Artery Disease
5-Year Outcomes of the PRECOMBAT Study
Jung-Min Ahn, MD,* Jae-Hyung Roh, MD,* Young-Hak Kim, MD,* Duk-Woo Park, MD,* Sung-Cheol Yun, PHD,y
Pil Hyung Lee, MD,* Mineok Chang, MD,* Hyun Woo Park, MD,* Seung-Whan Lee, MD,* Cheol Whan Lee, MD,*
Seong-Wook Park, MD,* Suk Jung Choo, MD,* CheolHyun Chung, MD,* JaeWon Lee, MD,* Do-Sun Lim, MD,z
Seung-Woon Rha, MD,x Sang-Gon Lee, MD,k Hyeon-Cheol Gwon, MD,{ Hyo-Soo Kim, MD,# In-Ho Chae, MD,**
Yangsoo Jang, MD,yy Myung-Ho Jeong, MD,zz Seung-Jea Tahk, MD,xx Ki Bae Seung, MD,kk Seung-Jung Park, MD*

ABSTRACT
BACKGROUND In a previous randomized trial, we found that percutaneous coronary intervention (PCI) was not inferior
to coronary artery bypass grafting (CABG) for the treatment of unprotected left main coronary artery stenosis at 1 year.
OBJECTIVES This study sought to determine the 5-year outcomes of PCI compared with CABG for the treatment of
unprotected left main coronary artery stenosis.
METHODS We randomly assigned 600 patients with unprotected left main coronary artery stenosis to undergo PCI
with a sirolimus-eluting stent (n 300) or CABG (n 300). The primary endpoint was a major adverse cardiac or
cerebrovascular event (MACCE: a composite of death from any cause, myocardial infarction, stroke, or ischemia-driven
target vessel revascularization) and compared on an intention-to-treat basis.
RESULTS At 5 years, MACCE occurred in 52 patients in the PCI group and 42 patients in the CABG group (cumulative
event rates of 17.5% and 14.3%, respectively; hazard ratio [HR]: 1.27; 95% condence interval [CI]: 0.84 to 1.90;
p 0.26). The 2 groups did not differ signicantly in terms of death from any cause, myocardial infarction, or stroke as
well as their composite (8.4% and 9.6%; HR, 0.89; 95% CI, 0.52 to 1.52; p 0.66). Ischemia-driven target vessel
revascularization occurred more frequently in the PCI group than in the CABG group (11.4% and 5.5%, respectively;
HR: 2.11; 95% CI: 1.16 to 3.84; p 0.012).
CONCLUSIONS During 5 years of follow-up, our study did not show signicant difference regarding the rate
of MACCE between patients who underwent PCI with a sirolimus-eluting stent and those who underwent CABG.
However, considering the limited power of our study, our results should be interpreted with caution. (Bypass Surgery
Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease [PRECOMBAT];
NCT00422968) (J Am Coll Cardiol 2015;65:2198206) 2015 by the American College of Cardiology Foundation.

From the *Heart Institute, University of Ulsan College of Medicine, Asan Medical Center, Seoul, South Korea; yDivision of
Biostatistics, Center for Medical Research and Information, University of Ulsan College of Medicine, Asan Medical Center, Seoul,
South Korea; zKorea University Anam Hospital, Seoul, South Korea; xKorea University Kuro Hospital, Seoul, South Korea; kUlsan
University Hospital, Ulsan, South Korea; {Samsung Medical Center, Seoul, South Korea; #Seoul National University Hospital,
Seoul, South Korea; **Seoul National University Hospital, Bundang, South Korea; yyYonsei University Severance Hospital, Seoul,
South Korea; zzChonnam National University Hospital, Gwangju, South Korea; xxAjou University Medical Center, Suwon, South
Korea; and the kkCatholic University of Korea, St. Marys Hospital, Seoul, South Korea. This study was supported by funds from
the CardioVascular Research Foundation, Seoul, South Korea; Cordis, a Johnson & Johnson Company, Miami Lakes, Florida; and
Health 21 R&D Project, Ministry of Health & Welfare, Seoul, South Korea (HI10C2020). The authors have reported that they have no
relationships relevant to the contents of this paper to disclose. Drs. Ahn and Roh contributed equally to this paper.
Manuscript received February 9, 2015; revised manuscript received March 5, 2015, accepted March 6, 2015.

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Stenting Versus CABG for Left Main Stenosis

atients undergoing revascularization of un-

PROCEDURES. The

protected left main coronary artery (ULMCA)

and CABG were described previously (5).

procedures

for

PCI

ABBREVIATIONS
AND ACRONYMS

stenosis are considered at high risk of adverse

Sirolimus-eluting stents were the default

cardiovascular events. Coronary artery bypass graft-

drug-eluting stents used during PCI. Use of

ing (CABG) had been considered the standard of

intravascular ultrasound, adjunctive devices,

care for ULMCA stenosis (1). However, over the

or glycoprotein IIb/IIIa inhibitors was at

past 20 years, improvements in stent technology

the operators discretion. All patients under-

and an accumulation of operator experience have

going PCI took aspirin plus clopidogrel (300-

increased the number of elective percutaneous coro-

mg loading dose) or ticlopidine (500-mg

event(s)

nary interventions (PCIs) performed to treat UMLCA

loading dose) before or during the procedure.

MI = myocardial infarction

stenosis (24). Subsequently, several large registries

After PCI, all patients were prescribed 100

and randomized, controlled studies have shown

mg/day aspirin indenitely and 75 mg/day

that PCI with a drug-eluting stent and CABG had

clopidogrel or 250 mg/day ticlopidine for at

TVR = target vessel

comparable incidences of death, myocardial infarc-

least 1 year. During CABG, the internal

revascularization

tion (MI), or stroke (57). Thus, recent guidelines

thoracic artery was preferred for bypass of the

ULMCA = unprotected

considered PCI to be a potential alternative to

left anterior descending artery. Medications

left main coronary artery

CABG for ULMCA stenosis (8). However, the durable

after CABG were given according to the policy of the

effect of PCI remains in debate, and there are limited

institution or the preference of the surgeon. During

existing data from long-term studies comparing PCI

the index procedure or repeated revascularization, the

and CABG.

decision of which lesion was to be revascularized was

CABG = coronary artery bypass

grafting

CI = condence interval
HR = hazard ratio
MACCE = major adverse
cardiac or cerebrovascular

PCI = percutaneous coronary

intervention

at the operators discretion.

SEE PAGE 2207

We present the 5-year results of the PRECOMBAT

(Bypass Surgery Versus Angioplasty Using SirolimusEluting Stent in Patients With Left Main Coronary
Artery Disease) study.

FOLLOW-UP AND ENDPOINTS. After PCI, all patients

were asked to undergo follow-up angiography 8

to 10 months after the procedure or earlier if they
were experiencing symptoms of angina. However,
routine follow-up angiography was not performed

METHODS

for patients who underwent CABG. All other followup assessments were performed at 1, 6, 9, and 12

STUDY DESIGN AND PATIENTS. The study design

months and yearly thereafter at a clinic visit or via a

and methods of the PRECOMBAT trial were previously

telephone interview.

reported (6). In brief, the PRECOMBAT trial was a

The primary endpoint was a major adverse cardiac

prospective, open-label, randomized trial conducted

or cerebrovascular event (MACCE) (a composite of

at 13 sites in South Korea. Patients considered eligible

death from any cause, MI, stroke, or ischemia-driven

to participate in the study were older than 18 years of

target vessel revascularization [TVR]) after randomi-

age and had received a diagnosis of stable angina,

zation. Secondary endpoints included the individual

unstable angina, silent ischemia, or nonST-segment

components of the primary endpoint; a composite of

elevation MI. All patients had newly diagnosed

death, MI, or stroke; and clinically driven TVR.

ULMCA stenosis (more than 50% diameter stenosis by

Deaths were considered cardiac unless an unequivo-

visual angiographic estimation) and had been judged

cal noncardiac cause was established. MI was dened

to be suitable candidates for either PCI or CABG. A

as the appearance of new Q waves and an increase in

complete list of inclusion and exclusion criteria is

the creatine kinase-myocardial band concentration to

provided in the Online Appendix. Patients were

more than 5 times the upper limit of the normal

randomly assigned to undergo PCI with sirolimus-

range, if occurring within 48 h after the procedure or

eluting stents or CABG in a 1:1 ratio. The institu-

as the appearance of new Q waves or an increase in

tional review board at each hospital approved the

the creatine kinase-myocardial band concentration

protocol,

to greater than the upper limit of the normal range,

and

all

patients

provided

written

informed consent.
The funder of the study had no role in study

plus ischemic symptoms or signs, if occurring more

than 48 h after the procedure. Stroke was dened

design, data collection, data analysis, data interpre-

as a sudden onset of neurological decit resulting

tation, or writing of the report. The corresponding

from vascular lesions of the brain and persisting

author had full access to all the data in the study and

for more than 24 h. TVR, in which repeat revascu-

had nal responsibility for the decision to submit for

larization with either PCI or CABG was performed in

publication.

the treated vessel, was considered to be driven by

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Stenting Versus CABG for Left Main Stenosis

ischemia if the stenosis of any vessel was at least

cumulative incidence were presented as number (%),

50% of the vessel diameter in the presence of

with the latter estimated using the Kaplan-Meier

ischemic signs or symptoms or if the stenosis was

method and compared between the 2 groups using

at least 70% of the vessel diameter, even in the

the log-rank test of the time to the rst event after

absence of ischemic signs or symptoms. Alterna-

randomization. Hazard ratios (HRs) and 95% con-

tively, TVR was considered clinically driven when

dence intervals (CIs) were estimated with the use of

the treated vessels had stenosis of at least 50% in

Cox proportional hazards models. The proportional

the presence of ischemic signs or symptoms. The

hazards assumption was checked with a graphical log-

event adjudication committee, whose members were

minus-log method. We also compared the primary

blind to the study group assignments, assessed all

endpoint between the 2 groups using Cox regression

clinical endpoints.

models with robust SEs to account for the clustering

effect of sites. The patients lost to follow-up were

STATISTICAL ANALYSIS. Assuming 13% incidence

included in the analyses for all outcomes by censoring

of the primary endpoint in the CABG group, a

at the data of last follow-up. We assessed the con-

noninferiority margin of 7%, and use of a Z test

sistency of treatment effects in the pre-specied

for hypothesis testing, the original PRECOMBAT

subgroups using Cox regression models with tests

trial was designed to have 80% power to show the

for interaction. For more explicit comparison with

noninferiority of PCI, with a 1-sided type I error rate

contemporary studies and guidelines, we added a

of 0.05. In this study, unless stated otherwise, all

subgroup analysis according to the SYNTAX tertile

analyses were performed on an intention-to-treat

from the SYNTAX (Synergy Between PCI With Taxus

basis. A descriptive analysis was performed by pre-

and Cardiac Surgery) trial. All statistical analyses

senting data as the mean  SD or number (%).

were performed using IBM SPSS version 21 (IBM,

Continuous variables were compared with a Student

Chicago, Illinois). A 2-tailed p value <0.05 was

t test or Wilcoxon rank sum test, and categorical

considered statistically signicant.

variables were compared with chi-square or Fisher

exact test, as appropriate. Five-year outcomes were

RESULTS

dened as events occurring within 1,825 days after

randomization. The number of events and their

STUDY PATIENTS. Between April 2004 and August

2009, a total of 600 eligible patients were randomly

assigned to undergo PCI with sirolimus-eluting
F I G U R E 1 Patient Distribution in the PRECOMBAT Study at the 5-Year Follow-Up

stents (n 300) or CABG (n 300). Of those, 279

patients (93%) in the PCI group and 275 patients
(91.7%) in the CABG group completed 5 years of

600 patients randomized

follow-up (Figure 1).

300 assigned to PCI

300 assigned to CABG

24 treated with CABG

276 treated with PCI
0 medically treated

248 treated with CABG

51 treated with PCI
1 medically treated

Baseline demographic and lesion characteristics

were previously described (7). In brief, the mean
age of patients was 61.8  10.0 years in the PCI

3 lost to FU
297 remained at 2 years
18 lost to FU

2 lost to FU
298 remained at 2 years
23 lost to FU

group and 62.7  9.5 years in the CABG group; 228

patients (76.0%) in the PCI group and 231 patients
(77.0%) in the CABG group were male; 102 patients
(34.0%) in the PCI group and 90 patients (30.0%) in
the CABG group had medically treated diabetes, of
whom 10 (3.3%) and 9 (3.0%), respectively, needed
insulin; 223 patients (74.4%) in the PCI group and
213 patients (71.0%) in the CABG group had left
main

279 remained at 5 years

275 remained at 5 years

plus

multivessel

involvement.

The

mean

SYNTAX score was 24.4  9.4 in the PCI group and

25.8  10.5 in the CABG group.
Selected procedural characteristics of the patients

The number of the patients randomized to each group, those who actually received the
assigned treatment, and those who were lost to follow-up are shown. CABG coronary
artery bypass grafting; FU follow-up; PCI percutaneous coronary intervention;
PRECOMBAT Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in
Patients With Left Main Coronary Artery Disease.

are as follows. In the PCI group, intravascular

ultrasound was used in 91.2%; the mean number
of stents implanted in left main coronary lesions
and per-patient was 1.6  0.8 and 2.7  1.4,
respectively. In CABG patients, 63.8% underwent

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Stenting Versus CABG for Left Main Stenosis

off-pump surgery; 93.6% underwent revascularization of the left anterior descending artery with left

T A B L E 1 Study Outcomes at the 5-Year Follow-Up

internal mammary artery.

Antiplatelet drug use was signicantly higher in
patients in the PCI group than in the CABG group

Endpoint

MACCE
Death from any cause

PCI
(n 300)

CABG
(n 300)

Hazard Ratio
(95% CI)

52 (17.5)*

42 (14.3)

1.27 (0.841.90)

0.26

17 (5.7)

23 (7.9)

0.73 (0.391.37)

0.32

p Value

throughout the study period. At 5 years, signicantly

Cardiac

11 (3.8)

20 (6.9)

0.54 (0.261.13)

0.098

more patients in the PCI group were receiving

Noncardiac

6 (2.0)

3 (1.1)

1.98 (0.497.91)

0.33

dual-antiplatelet therapy than in the CABG group

Myocardial infarction

6 (2.0)

5 (1.7)

1.20 (0.373.93)

0.76

Q-wave MI

4 (1.4)

3 (1.0)

1.33 (0.305.95)

0.71

NonQ-wave MI

2 (0.7)

2 (0.7)

0.99 (0.147.06)

1.00

2 (0.7)

2 (0.7)

0.99 (0.147.02)

0.99
0.66

(Online Table 1).

STUDY ENDPOINTS. The cumulative incidences of

Stroke

the clinical outcomes are described in Table 1,

Death, MI, or stroke

25 (8.4)

28 (9.6)

0.89 (0.521.52)

the Central Illustration, and Figure 2. At 5 years, the

Repeat revascularization

38 (13.0)

21 (7.3)

1.86 (1.093.17)

0.020

36 (12.4)

18 (6.3)

2.05 (1.173.62)

0.011

cumulative incidence of MACCE was 17.5% in the

TVR

PCI group and 14.3% in the CABG group (HR: 1.27;

Ischemia driven

33 (11.4)

16 (5.5)

2.11 (1.163.84)

0.012

95% CI: 0.84 to 1.90; p 0.26). Analysis after

Clinically driven

27 (9.3)

15 (5.2)

1.83 (0.973.44)

0.057

50 (16.8)

40 (13.7)

1.28 (0.851.94)

0.24

adjustment

for

between-site

variability

showed

results similar to those from the original analysis

(HR: 1.27; 95% CI: 0.83 to 1.93; p 0.28). The rate of
the composite of death from any cause, MI, or stroke
was also similar between the 2 groups (8.4% and
9.6%, respectively; HR: 0.89; 95% CI: 0.52 to 1.52;
p 0.66), without signicant differences in the in-

Death, MI, or ischemia-driven TVR

Values are n (%) unless otherwise indicated. *Percentages are Kaplan-Meier estimates from the intention-totreat analysis. A log-rank test was used to calculate p values. Ischemia-driven TVR was dened 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 ischemiadriven TVR.
CABG coronary artery bypass grafting; CI condence interval; MACCE major adverse cardiac or cerebrovascular event(s); MI myocardial infarction; PCI percutaneous coronary intervention; TVR target vessel
revascularization.

dividual components (Central Illustration). Ischemiadriven TVR was more likely to occur in the PCI
group than in the CABG group (11.4% and 5.5%; HR:
2.11; 95% CI: 1.16 to 3.84; p 0.012) (Figure 2). In a
landmark analysis (Online Figure 1), the risk of
ischemia-driven TVR in the PCI group was more
obvious 1 year after randomization. An analysis of an
as-treated basis is shown in Online Table 2. Denite or
probable stent thrombosis occurred in 2 patients,
with a 5-year cumulative incidence of 0.3%.

(7). The current 5-year results of the study showed

that there were no signicant differences in the rate
of MACCE between patients assigned to PCI with
sirolimus-eluting

stents

and

those

assigned

to

CABG, which conrmed and extended the results

observed at 1 year (Central Illustration). In addition,
the rate of the composite of death, MI, or stroke
was

similar

between

the

groups.

However,

more

frequently

SUBGROUP. Formal testing for interactions showed

ischemia-driven

that the results of the comparison of the 5-year rate

in the PCI group than in the CABG group. These

of MACCE between PCI and CABG were consistent

results are supported by data from observational

TVR

occurred

across multiple subgroups except for those dened

studies (912), a small randomized study (13), and a

according to angiographic left main coronary artery

meta-analysis of patients with long-term follow-up

stenosis (>70% vs. 50% to 70%) (Figure 3). Across the

(14). Recently, 5-year outcomes of the left main

3 subgroups dened by SYNTAX score tertiles, the

subgroup in the SYNTAX study also showed a

rates of MACCE and the composite of death from any

similar trend, with no differences in the rate of

cause, MI, or stroke were not signicantly different

MACCE between the PCI and CABG groups (15).

between the 2 groups (Online Table 3, Online

The rates of overall adverse events in our study

Figure 2). In the high SYNTAX score ($33) group,

were lower than those reported in the SYNTAX study.

the rate of ischemia-driven TVR was signicantly

The main differences were that we used sirolimus-

higher in the PCI group than in the CABG group.

eluting stents as the default stent, and we used

intravascular ultrasound in more than 90% of pa-

DISCUSSION

tients for stent optimization (1618). We considered

reasonably incomplete, but functionally adequate

The PRECOMBAT study was a randomized trial

stent implantation in the nonleft main coronary

comparing PCI with drug-eluting stents and CABG,

artery stenosis to avoid an excess of stent and related

focusing on patients with ULMCA stenosis. The

events (19). In addition, differences in patient char-

1-year outcomes of the study showed the non-

acteristics, presentation, and lesion complexity may

inferiority of PCI to CABG with respect to MACCE

be possible contributing factors. Nevertheless, the

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Stenting Versus CABG for Left Main Stenosis

F I G U R E 2 Kaplan-Meier Cumulative Event Curves for the Individual Clinical Events at the 5-Year Follow-Up

PCI

Cumulative Incidence, %

Death from any cause

30
25
20
p=0.32

15
10

7.9%

5.7%

2
3
4
Years Since Randomization
292
289
283
277
291
288
281
273

20
p=0.76

15
10

2.0%
1.7%

262
252

Stroke

30
25
20
p=0.99

15
10

0.7%
0.7%

0
Patient at risk
PCI
300
CABG
300

30
Cumulative Incidence, %

0
Patient at risk
PCI
300
CABG
300

Cumulative Incidence, %

25

Myocardial infarction

30
Cumulative Incidence, %

CABG

2
3
4
Years Since Randomization
288
284
278
271
289
286
279
270

5
257
249

Ischemia-driven target vessel revascularization

25
20
p=0.012

15

11.4%

10
5.5%

5
0

0
Patient at risk
PCI
300
CABG
300

2
3
4
Years Since Randomization
292
289
282
276
289
286
279
271

5
261
250

0
Patient at risk
PCI
300
CABG
300

2
3
4
Years Since Randomization
274
263
254
248
283
278
271
261

5
232
240

Shown are rates of the death of any cause (A), myocardial infarction (B), stroke (C), and ischemia-driven target vessel revascularization (D).
Abbreviations as in Figure 1.

rate of TVR signicantly increased in the PCI group at

group. Consequently, the rate of MACCE was similar

5 years compared with the CABG group. Given a

between groups. Although the absence of any dif-

higher rate of repeat revascularization, even after the

ference between the groups in our study is not

use of second-generation drug-eluting stents for

easily explained, possible causes are our studys

ULMCA stenosis, frequent repeat revascularization

low event rates and limited statistical power. In

could be an inherent weakness of stent-related

addition, the different ethnicities in our study and

treatments (20). However, the observed increase in

the SYNTAX study could be another contributing

repeat revascularization in the PCI group did not

factor.

appear to translate into an increase in hard end-

Unlike the situation in multivessel disease (21,22),

points, such as death, MI, or stroke, although a

both PCI and CABG showed similar rates of the com-

further study with longer follow-up and larger

posite of death, MI, or stroke in patients with ULMCA

number of subjects will be needed.

stenosis. The reason for this difference in outcomes

With respect to the occurrence of stroke, there

between ULMCA stenosis and multivessel stenosis is

was no signicant difference between PCI and

unclear, but ULMCA stenosis might be a more

CABG in our study. However, in the SYNTAX study,

attractive target for PCI because of its larger caliber,

although the rate of repeat revascularization was

shorter lesion length, and lack of tortuosity compared

signicantly higher in the PCI group, this was offset

with

by a signicantly higher rate of stroke in the CABG

(Evaluation of Xience Prime or Xience V Versus

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multivessel

disease.

The

ongoing

EXCEL

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Stenting Versus CABG for Left Main Stenosis

F I G U R E 3 Subgroup Analysis

MACCE

Subgroup

Hazard Ratio (95% CI)

P value

PCI
CABG
n / total n. (%)
Overall

1.27 (0.84-1.90)

52/300 (17.5) 42/300 (14.3)

0.26

P value for
Interaction

0.86

Age
65 yr

24/129 (18.8) 23/149 (15.8)

1.23 (0.70-2.18)

0.47

<65 yr

28/171 (16.5)

19/151 (12.8)

1.33 (0.74-2.38)

0.33

Male

39/228 (17.3) 30/231 (13.3)

1.35 (0.84-2.17)

0.21

12/69 (17.5)

1.06 (0.48-2.31)

0.89

>70%

20/140 (14.4) 27/159 (17.4)

0.83 (0.47-1.48)

0.53

50-70%

32/160 (20.2) 15/141 (10.9)

1.98 (1.07-3.65)

0.027

0.48 (0.09-2.47)

0.37
0.98

Sex

0.60
Female

13/72 (18.1)

0.043

Left main coronary artery stenosis

0.14

Coronary artery disease distribution

Left main only

2/27 (7.4)

5/34 (14.8)

4/50 (8.0)

4/53 (7.7)

1.02 (0.25-4.07)

LM with double-vessel disease

16/101 (16.0)

17/90 (19.2)

0.83 (0.42-1.64)

0.59

LM with triple-vessel disease

30/122 (24.8) 16/123 (13.3)

2.09 (1.14-3.84)

0.015

37/200 (18.7) 26/183 (14.7)

1.34 (0.81-2.22)

0.25

15/111 (13.6)

1.14 (0.56-2.33)

0.73

Yes

33/149 (22.3) 24/159 (15.5)

1.56 (0.92-2.64)

0.095

No

19/151 (12.7)

18/141 (13.0)

0.97 (0.51-1.85)

0.93

Yes

25/140 (17.9) 27/163 (16.8)

1.07 (0.62-1.85)

0.79

No

27/160 (17.1)

15/137 (11.4)

1.63 (0.87-3.06)

0.13

Yes

23/102 (22.7)

15/90 (16.9)

1.39 (0.73-2.67)

0.32

No

29/198 (14.8) 27/210 (13.2)

1.16 (0.69-1.96)

0.58

0-22

16/129 (12.5) 13/104 (13.0)

0.98 (0.47-2.05)

0.97

23-32

22/102 (21.7)

12/97 (12.6)

1.85 (0.91-3.73)

0.083

33

14/58 (24.2)

13/68 (19.2)

1.37 (0.64-2.91)

0.41

Left main with single-vessel disease

Bifurcation involvement
Yes
No

0.71
15/99 (15.2)

0.27

Right coronary artery involvement

0.35

Acute coronary syndrome

0.66

Diabetes

Syntax score

0.49

0.1
PCI Better

10
CABG Better

Subgroup analyses with hazard ratios and 95% condence intervals are shown for the primary endpoint of the composite of death of any cause, myocardial infarction,
stroke, or ischemia-driven target vessel revascularization among subgroups of patients randomized to undergo PCI or CABG. The p value for interaction represents the
likelihood of interaction between the variable and the relative treatment effect. CI condence interval; LM left main; MACCE major adverse cardiac or cerebrovascular event(s); other abbreviations as in Figure 1.

CABG for Effectiveness of Left Main Revasculariza-

strategy between treatments. Even in patients with

tion) trial comparing a 3-year composite endpoint of

the highest baseline SYNTAX scores ($33), no signif-

death, MI, or stroke in patients treated with PCI using

icant difference between treatment groups for the

second-generation drug-eluting stents and CABG

primary endpoint was reported. Although this might

will provide important information in this regard.

be primarily due to insufcient statistical power, the

Current clinical guidelines have adopted the

utility of the SYNTAX score for this purpose still

SYNTAX score to aid in selection of the appropriate

needs to be evaluated (21,2325). Recent approaches

revascularization strategy for ULMCA stenosis (8).

combining anatomic and clinical factors could be

However, our study showed that the SYNTAX score

promising for a more accurate personalized assess-

tertile did not discriminate the more appropriate

ment of patient risk (25).

Downloaded From: [Link] by Timothy Byrnes on 06/28/2015

2204

Ahn et al.

JACC VOL. 65, NO. 20, 2015

Stenting Versus CABG for Left Main Stenosis

MAY 26, 2015:2198206

CE N TR AL I LLUSTR A TI ON Stenting Versus CABG for Left Main Stenosis: Kaplan-Meier Cumulative Event Curves of the
Primary Endpoint and the Major Secondary Endpoint at the 5-Year Follow-Up

Ahn, J-M. et al. J Am Coll Cardiol. 2015; 65(20):2198206.

(Top) The cumulative incidence of major adverse cardiac or cerebrovascular events (the composite of death from any cause, myocardial infarction, stroke,
or ischemia-driven target vessel revascularization). (Bottom) The composite of death of any cause, myocardial infarction, or stroke. CABG coronary
artery bypass graft; PCI percutaneous coronary intervention.

Downloaded From: [Link] by Timothy Byrnes on 06/28/2015

Ahn et al.

JACC VOL. 65, NO. 20, 2015

MAY 26, 2015:2198206

Stenting Versus CABG for Left Main Stenosis

In the subgroup analysis, there was a signicant

sirolimus-eluting stent and those who underwent

interaction between angiographic stenosis of the

CABG, supporting current guidelines stating that

left main coronary artery and treatment strategies

left main stenting is a feasible revascularization

for the primary endpoint. The reason was unclear,

strategy for patients with suitable coronary anatomy.

and this unexpected nding is likely due to the play

However, considering the limited power of our study,

of chance. In addition, patients with left main dis-

our results should be interpreted with caution.

ease plus 3-vessel disease showed better outcomes

with CABG than with PCI, suggesting caution in the
use of PCI for left main disease in patients with
3-vessel coronary artery disease or advanced coronary artery disease.

ACKNOWLEDGMENTS The authors thank the staff of

the PRECOMBAT trial, the members of the cardiac

catheterization

laboratories

at

the

participating

centers, and the study coordinators for their efforts

in collecting clinical data and ensuring the accuracy

STUDY LIMITATIONS. First, although we tried to

and completeness of the data.

enroll all comers, as in other randomized studies, it

was possible that we enrolled selected patients with

REPRINT REQUESTS AND CORRESPONDENCE: Dr.

relatively

crossovers,

Seung-Jung Park, Heart Institute, Asan Medical

particularly from PCI to CABG, may have introduced

Center, University of Ulsan, 388-1 Pungnap-dong,

bias. Third, this study did not have adequate power to

Songpa-gu, Seoul 138-736, South Korea. E-mail:

compare hard endpoints, such as death, MI, and

sjpark@[Link].

low-risk

proles.

Second,

stroke. Fourth, owing to the limited sample size, the

results of our subgroup analyses should be considered hypothesis generating at best. Fifth, the systematic performance of follow-up angiography in
the PCI group may have increased the rate of TVR.
Smaller and statistically insignicant HR for clinically
driven TVR, compared with that for ischemia-driven
TVR, probably supports this hypothesis. Finally,
clinical outcomes may have been affected by unequal
use of antiplatelet agents between the 2 groups
(Online Table 1).

outcomes of revascularization for patients with LMCA stenosis

managed by PCI did not differ signicantly in terms of the
composite endpoint of all-cause mortality, MI, stroke, or
target vessel revascularization from those in patients undergoing
CABG surgery.

number of patients and longer follow-up are needed to provide

adequate statistical power to establish the optimal revasculari-

During the 5-year follow-up, our study did not

show a signicant difference in the rate of MACCE
patients

COMPETENCY IN MEDICAL KNOWLEDGE: Over 5 years,

TRANSLATIONAL OUTLOOK: Additional studies of a larger

CONCLUSIONS

between

PERSPECTIVES

who

underwent

PCI

with

zation strategy for the prevention of death, MI, and stroke in

patients with LMCA stenosis.

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KEY WORDS coronary artery bypass

grafting, long-term outcome,
percutaneous coronary intervention

A PPE NDI X For an expanded Methods

section, a list of the participating investigators,
and supplemental tables and gures, please
see the online version of this article.