DOI: 10.1161/CIRCULATIONAHA.113.006689
Five-Year Outcomes in Patients with Left Main Disease Treated with Either
Percutaneous Coronary Intervention or Coronary Artery Bypass Grafting in
the SYNTAX Trial
Running title: Morice et al.; SYNTAX LM Subgroup Outcomes at 5 years
Marie-Claude Morice, MD1; Patrick W. Serruys, MD, PhD2; A. Pieter Kappetein, MD, PhD2;
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Ted E. Feldman, MD3; Elisabeth Ståhle, MD4; Antonio Colombo, MD5; Michael J. Mack, MD6;
David R. Holmes, MD7; James W. Choi, MD8; Witold Ruzyllo, MD9; Grzegorz Religa, MD9;
Jian Huang, MD, MS10; Kristine Roy, PhD10; Keith D. Dawkins, MD10; Friedrich Mo
Mohr
Mohr,
hr, MD
hr
MD,, Ph
PhD
D11
1
Institut Cardiovasculaire Paris Sud, Hopital Privé Jacques Cartier, Générale de santé, Massy,
Fran
France;
an
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Erasmus
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Rotterdam,
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IL; Un
University
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Hos
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Upppsaala, Uppsala,
Up
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San
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Scientific
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Germany
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Address
for
Add
Ad
d
f Correspondence:
C
d
Marie-Claude Morice, MD, FESC, FACC
Head of Institut Cardiovasculaire Paris Sud
Hopital Privé Jacques Cartier
Générale de santé,6, Avenue du Noyer Lambert
Massy, 91349 France
Tel: +33 (016) 013-4602
Fax: +33 (016) 013-4603
E-mail: [email protected]
Journal Subject Codes: Cardiovascular (CV) surgery:[36] CV surgery: coronary artery disease,
Treatment:[24] Catheter-based coronary interventions:stents
1
DOI: 10.1161/CIRCULATIONAHA.113.006689
Abstract
Background—Current guidelines recommend coronary artery bypass graft surgery (CABG)
when treating significant de novo LM stenosis; however, percutaneous coronary intervention
(PCI) has a Class IIa indication for unprotected LM disease in selected patients. This analysis
compares 5-year clinical outcomes in PCI- and CABG-treated LM patients in the SYNTAX trial,
the largest trial in this group to date.
Methods and Results—SYNTAX randomized 1800 LM and/or 3-vessel disease patients to
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
receive either PCI (with TAXUS Express paclitaxel-eluting stents) or CABG. The unprotected
LM cohort (N=705) was predefined and powered. MACCE at 5 years was 36.9% in
in PCI
P I patients
PC
p ti
pa
tien
ents
and 31.0% in CABG patients (hazard ratio (HR) 1.23 [0.95, 1.59]; P=0.12). Mortality
Mort
rtal
alit
al
ityy was
it
waas 12.8%
12.8%
8%
and 14.6% in PCI
C and CABG patients, respectively
y (HR 0.88 [0.58, 1.32], P=0.53). Stroke was
significantly
ign
gniific
ifi antl
tlyy increased
i cr
in
crea
e se
ea
sedd in
i the
the CABG
CA
ABG
B group
gro
roup
upp (PCI
(PC
PCII 1.5%
1.55% vs
vs CABG
CA G 4.3%,
4.3
.3%,
%,, HR
HR 0.
0.33
33 [[0.12,
0.12
0.
12,, 0.
00.92],
922],
P=0.03)
andd re
revascularization
arm
(26.7%
HR
[1.28,
2.57],
P=0
P=
0.
0.03)
rrepeat
peeat rev
vascu
ulariza
ri ati
t on
n in
in the
the PC
PCI ar
rm (2
26.
6.7%
7% vvss 15.
115.5%,
5.5%,, H
R 1.82
82 [1
1.228, 2.
.57],,
P<0.01).
P<0.
0.01
01)). MACCE
MAC
ACCE
C was
was
a similar
sim
imilar
ar between
bet
etween arms
arm
rmss in patients
patien
ents
ts with
wit
ithh low/intermediate
low/
lo
w/in
inte
term
rmed
ediaatee SYNTAX
SYN
YNTA
TAX
X Scores
Scor
Sc
orees
increased
PCI
patients
with
but significantly
but
sign
si
gnif
ific
ican
antl
tlyy in
incr
crea
ease
sedd in P
CI pa
pati
tien
ents
ts w
ithh hi
it
high
gh sscores
core
co
ress ((•33).
•33
33))
Conclusions—At 5 years, no difference in overall MACCE was found between treatment groups.
PCI-treated patients had a lower stroke but higher revascularization rate versus CABG. These
results suggest that both treatments are valid options for LM patients. The extent of disease
should accounted for when choosing between surgery and PCI as patients with high SYNTAX
scores seem to benefit more from surgery compared to the lower terciles.
Clinical Trial Registration Information—clinicaltrials.gov. Identifier: NCT00114972.
Key words: percutaneous coronary intervention, stent, left main coronary artery disease,
SYNTAX score, SYNTAX
2
DOI: 10.1161/CIRCULATIONAHA.113.006689
Introduction
The optimal revascularization strategy (coronary artery bypass surgery [CABG] or percutaneous
coronary intervention [PCI]) for patients with complex coronary artery disease is a continuing
topic of debate. Patients undergoing revascularization of unprotected left main coronary artery
(LM) lesions are considered at high risk for adverse cardiovascular events. Several large studies
and meta-analyses have compared outcomes in patients treated with either CABG or PCI with
stenting; most have found similar intermediate and long-term safety outcomes (i.e., mortality and
MI), lower stroke rates, but an increased need for repeat revascularization with PCI compared
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
with CABG; a few studies have also demonstrated differences in long-term survival with
CABG1-7. This analysis evaluated the 5 year outcomes of the predefined LM subg
subgroup
bg
gro
oup
p ooff
patients randomly assigned to receive PCI or CABG in the SYNTAX trial.
Methods
M
etthods
th
Methods
M
Meth
eth
hod
ods forr the
the SYNTAX
SYNT
SY
NT
TAX trial
trial
riall have
hav
ve bbeen
e n pr
ee
prev
previously
vio
iouusly
y ddescribed
esscr
crib
ib
bed iin
n full
fu ((8-10)
8-10
810)) an
and
nd ar
are
re ssummarized
umm
mmar
mm
ariizeed
here.
here
he
re. Th
re
Thee Sy
Syn
Synergy
ner
ergy
gy B
Between
etwe
et
ween
we
en P
PCI
CI W
With
ithh TA
it
TAX
TAXUS
XUS aand
nd C
Cardiac
ardi
ar
diac
di
ac Surgery
Sur
urge
gery
ge
ry (SYNTAX)
(SY
SYNT
NTAX
NT
AX)) trial
AX
tria
tr
iall was
ia
was a
prospective, randomized, international, multicenter trial conducted in 17 countries. The study was
conducted in accordance with the US Food and Drug Administration Guidance for Industry E6
Good Clinical Practice: Consolidated Guidance, the Declaration of Helsinki, the International
Conference on Harmonisation, and all local regulations, as appropriate. Institutional Review
Boards at each center approved the study protocol and all patients provided written informed
consent. The study is registered at www.clinicaltrials.gov under identifier NCT00114972.
Subject Selection, Procedure, and Follow Up
Patients with LM and/or 3-vessel disease with no previous history of CABG or PCI were
assessed a priori using a Heart Team conference approach, including an interventional
3
DOI: 10.1161/CIRCULATIONAHA.113.006689
cardiologist and a cardiac surgeon, to determine the appropriate method for revascularization
(CABG or PCI). If, by consensus, the patient could be offered equivalent revascularization by
either technique, the patient was randomized to receive either CABG or PCI with TAXUS
Express stents, stratified by LM disease and diabetes. Patients considered ineligible for one
technique were entered into 1 of 2 parallel nested registries (the CABG registry for PCIineligible patients and the PCI registry for CABG-ineligible patients). The primary endpoint of
the trial was noninferiority of the rate of major adverse cardiac and cerebrovascular events
(MACCE) at 1 year for the PCI arm compared with the CABG arm. All patients in the
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
randomized cohort were required to have clinical follow-up yearly through 5 years8-10.
Definitions
Definitions of MACCE and other outcomes have been previously described8,10. In brief, MACCE
was de
was
defi
fine
fi
need aass tthe
he ccomposite
omposite of all-cause death,, my
myocardial infarction
infarrct
c ionn (M
(MI), stroke and repeat
defined
revascularization
evaasc
s ularizattio
ionn (via
(via
ia PCI
CI or
or CABG).
CABG
CA
BG).
BG
) Per
Per protocol
prrotocool symptomatic
sym
mptom
ptom
mat
atic
icc graft
gra
rafft oc
occl
occlusion
cluusio
usio
ionn an
andd st
stent
ten
nt
thrombosis
hro
omb
mbos
osis
iss w
were
eree ddefined
er
efi
finnedd aass eeither:
ithe
it
her:
he
r: ii)) cclinical
lin
nic
icaal
al pr
pres
presentation
essen
nta
t ti
t on ooff an aacute
cu
ute ccoronary
orrona
ronaary ssyndrome
ynddrom
yn
om
me wi
with
ith
h
documentatio
documentation
on of a flow
flo
ow limiting
liimi
miti
t ng thrombus
thro
r mb
mbus
u or
us
or occlusion
o cl
oc
clus
ussio
i n within
with
wi
thin
th
in a bypass
byypa
pass
ss graft
gra
raft
ft or
or ad
adja
adjacent
jace
ja
c nt to the
anastomosis of a previously bypassed coronary artery (for CABG patients), or within or adjacent
to a previously successfully treated artery (for PCI patients); ii) a Q-wave MI in the territory of
•1 treated vessels within first 30 days (d). All MACCE, Graft Occlusion (GO) and Stent
Thrombosis (ST) events were adjudicated by an independent clinical events committee.
Secondary endpoints included: overall MACCE rate and the rates of the individual components
of MACCE at 1 month post-procedure and at 6 months, 3 and 5 years post-allocation.
Statistical Methods
Initial enrollment was set at 1500 patients but was raised to 1800 to obtain a sufficient number of
4
DOI: 10.1161/CIRCULATIONAHA.113.006689
LM subjects (700) to detect a difference in 12-month MACCE between the PCI and CABG arms.
However, due to the hierarchical nature of the primary endpoint analysis although the subset of
LM patients was powered because the primary endpoint was not met the results reported here
should be considered hypothesis-generating. Procedural and outcomes analyses include all
lesions in patients with LM disease (with or without additional vessel involvement). Continuous
variables were expressed as means ± standard deviations (SD) and compared using a 2-sided
Students t-test. Binary variables were expressed as counts and percentages and compared using
Chi-square test. Significance was set at P<0.05. Fisher’s exact test was used in place of the Chi
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
square test when the total number of samples was ”40 and/or at least 1 cell count in the
ated
ted byy tthe
he
contingency table had an expected value <5. Cumulative event rates were estima
estimated
Kaplan-Meier method; log-rank test statistics and p-values were calculated to assess differences
beetw
wee
eenn treatment
trea
tr
e tmen
ea
tmen
nt groups
g oups for long term follow-up
gr
up endpoints.
endpoints. Thee Gree
eeenw
nwood formula for the
between
Greenwood
tan
nda
d rd errorr w
as used
useed to calculate
calc
alcula
culaate tthe
he 2-sided
2-siided 95
5% CI
CI of
of the
th
he Kaplan-Meier
Kaplan
Kap
plan-M
-Mei
-M
eieer
er event
eve
vent
n rrates.
nt
ates
at
e . Ha
es
Haza
zaard
standard
was
95%
Hazard
ati
tioo an
andd 95
5% co
onffid
ideenc
ence
ce iintervals
ntter
e va
vals
ls aare
ree ffrom
rom
ro
m Co
Cox’
x’s pa
ppartial
rtiaal like
llikelihood
ikeeli
l hood
hood m
ettho
hodd. P
atiien
at
ients we
ere aalso
lsso
ratio
95%
confidence
Cox’s
method.
Patients
were
posst hoc
hoc by baseline
bas
a ellin
inee SYNTAX
SYNT
SY
NTAX
NT
AX score
sco
core
re tercile
ter
erci
c le (lo
ci
low
lo
w ”22,
”222, in
iintermediate
term
te
rmed
rm
edia
ed
iate
ia
t 223
te
3 to 332,
2 and high
2,
analyzed post
(low
•33) for 5-year MACCE outcomes. Statistical analyses were performed using SAS Software
Version 9.1 (Cary, NC).
Results
Patients
A total of 705 patients with LM lesions were enrolled in the randomized arm of SYNTAX
(Figure 1). Of these, follow-up data to 5 years are available in 96.9% of patients who underwent
PCI with TAXUS Express stents and 92.5% of patients randomized to CABG (Figure 1).
Baseline patient and lesion characteristics were well-balanced between groups and have been
5
DOI: 10.1161/CIRCULATIONAHA.113.006689
previously published along with the 1 year clinical outcomes11.
MACCE Outcomes at 5-years
MACCE and its components were analyzed in a time to event manner over 5 years in the LM
cohort. The non-significant differences in outcomes in each arm of the trial persisted after 1 year
of follow-up. Total MACCE at 5 years was 36.9% in patients who received PCI compared with
31.0% in CABG patients (hazard ratio 1.23 [0.95, 1.59]; P=0.12; Figure 2, Table 1) which was
mainly related to differences in repeat revascularization. The composite safety endpoint of
death/stroke/MI was not significantly different between treatment groups at 5-years postDownloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
randomization (PCI 19.0% vs CABG 20.8%; HR 0.91 [0.65, 1.27]; P=0.57; Figure 2, Table 1).
All-cause death, cardiac death and MI rates were not significantly different betw
between
weenn grou
ggroups
rou
oups
ps ((allallal
cause death: PCI 12.8% vs CABG 14.6%; HR0.88 [0.58, 1.32] P=0.53; cardiac death: PCI 8.6%
vss CABG
CAB
ABG
G 7.2%;
7.2%
7.
2 ; HR
HR 1.23 [0.71, 2.11] P=0.46; MI:
MI: PCI
PCI 8.2% vs CABG
C BG
CA
G 4.8%;
4.8%; HR 1.67 [0.91,
Figure
stroke
was
33.10]
.10
0] P=0.10; Fi
Figu
gu
ure 22,, Table
Tabl
Ta
blee 1).
bl
1). IIn
n ccontrast,
ontrasst,, stro
ok e w
as ssignificantly
as
ign
nif
ifiicantl
antlyy increased
in
ncr
creeas
eased
sed in CABG
CAB
ABG
G
randomized
LM
patients
HR
and
ndom
omiz
om
ized
ed
dL
M pa
ati
tien
en
ntss ((PCI
PC
CI 11.5%
.5%
5% vvss CA
CABG
BG 44.3%;
.3
3%;
%; H
R 0.33
0. 3 [[0.12,
0.12
12
2, 0.92]
0.92
2] P=0.03).
P=0.
P=0.
0 03
3). Repeat
Reepe
epeat
eat
revascularization
evascularizat
attio
ionn was
was significantly
siign
gnif
ific
if
ican
ic
ntl
tlyy increased
incrrea
in
ease
sedd in PCI
se
PCI
C randomized
ran
ndo
domi
mize
mi
zedd patients
ze
paati
t en
ents
ts (PCI
(PC
P I 26.7%
26.7
26
.7%
.7
% vs CABG
15.5%; HR 1.82 [1.28, 2.57], P<0.01; Figure 2, Table 1). Of the repeat revascularizations, the
majority were treated with repeat PCI, with 21.6% of PCI patients and 13.8% of patients in the
CABG arm undergoing additional PCI within 5 years (P<0.01). Repeat revascularization with
CABG occurred in 7.9% of PCI patients and 1.7% of CABG patients over 5 years (P<0.001).
Over 5 years, symptomatic graft occlusion (GO) occurred in 14 LM patients in the
CABG arm (4.4%) and symptomatic stent thrombosis occurred in 17 (5.1%) in the PCI arm
(P=0.70). In the CABG arm, two patients experienced an acute (” 1day post index procedure)
graft occlusion which led to an MI requiring revascularization. One patient had a subacute (2-30
6
DOI: 10.1161/CIRCULATIONAHA.113.006689
days) GO that received no intervention. The majority of GO were either late (31-365 days; N=5)
or very late (>366 days; N=6). Of these, two GOs led to an MI, one was revascularized with PCI
and 1 was not treated. All other GOs were revascularized with PCI. In the PCI arm, 17 LM
patients experienced a symptomatic stent thrombosis (ST) over 5 years (5.1%). Of these, 7
patients had a subacute ST leading to death in 4 cases, an MI in 1 case and repeat PCI in 2
patients. Two patients experienced a late and 8 patients experienced a very late ST. One patient
died and 4 had MIs which were revascularized. ST in the remaining 5 patients were treated with
repeat CABG (N=3) or PCI (N=2).In 6 patients, the ST was located in the LM leading to death in
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
2 cases.
CABG,
N=37
The subgroup of LM patients with diabetes consists in 67 patients (N=30
0C
ABG,
AB
G, N
=377
=3
PCI). Though clearly underpowered for analysis, similar to the overall cohort the observed
MACCE
MA
ACC
CCE
E seems
seem
se
em
ms comparable
com
co
mparable between treatment groups,
grouups, the only statistical
sta
t tist
stic
icaal
ic
al difference being
increased
revascularization
Table
ncrrea
e sed reva
asc
scul
ular
ul
ariz
izat
iz
atio
ionn rate
io
rate
rat
te with
wit
i h PCI
PC (Supplementary
(S
Sup
ppleemen
ntary
nta
ary Tab
T
able 11).
)
).
Outcomes
Stratified
Baseline
SYNTAX
Score
Ou
utc
tcom
omes
om
ess S
trattif
trat
ifiied
ied byy B
assel
elin
inee SY
in
S
NTAX
NT
AX S
coree
co
Rates of MACCE
MAC
AC
CCE and
and its
its
t components
com
ompo
one
n nt
nts were
were similar
sim
imil
illar between
b tw
be
wee
eenn LM patients
pat
atie
ient
ie
ntss receiving
nt
rece
re
c iv
ce
ivin
ingg PC
in
PCI or CABG
G
at 5-years in the lower two SYNTAX Score terciles (scores between 0-32; Figure 3, Table 2).
There appeared to be a survival advantage in LM patients with scores ”32 treated with PCI
(Table 2). In contrast, the likelihood of experiencing a MACCE event was increased in PCI
compared with CABG patients with high SYNTAX Scores (•33; Figure 3, Table 2). In the
group of patients with high SYNTAX Scores, MACCE, as well as cardiac death, and
revascularization were all significantly increased in patients receiving PCI; whereas stroke and
MI occurred at similar rates between treatment arms.
7
DOI: 10.1161/CIRCULATIONAHA.113.006689
Discussion
The SYNTAX study is the largest randomized comparison of PCI versus CABG for the
treatment of patients with LM disease. No significant differences were found between groups for
5-year MACCE. This confirms and extends the results observed at 1 year which also showed no
significant differences in MACCE in this LM subgroup of patients, in contrast with the global
cohort where the results were clearly in favor of surgery11. Additionally, outcomes in patients
with LM coronary artery disease have been shown to be related to the severity (or complexity) of
the downstream disease, rather than the actual presence of LM coronary artery disease12, which
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
the present analysis corroborates.
Although overall MACCE in the LM subgroups was prespecified and powered;
po
owe
were
r d; the
the
SYNTAX trial used a hierarchical statistical testing plan whereby testing of the LM subgroup
would
woul
wo
uldd occu
ul
ooccur
ccu
curr oonly
nly
ly
y iiff primary endpoint was met. T
The
hee non-inferiori
non-inferiority
ity end
endpoint
nd
dpoint
po of 12-month
MACCE
MACC
MA
C E was not
not met
met inn the
the overall
overa
veraall population;
poopu
pulati
tiionn; thus,
th
hus, the
th
he analysis
an
nalys
ysiis
is ooff LM ppatients
attie
ient
ntss pr
ppresented
e ente
es
tedd he
te
here
r
10,13
13
should
hypothesis-generating
hou
ould
ld be
be considered
connsid
co
nsid
derred observational
obser
bserva
vaatio
ona
nall an
andd hy
hyp
poth
poth
hes
e is-g
-geener
-g
ener
erat
atin
at
ingg10
. Ho
H
However,
weve
we
ver,
r, cconsistent
on
nsi
sissten
nt wi
w
with
th
h
other random
miz
ized
e ttrials
ed
rial
ri
alls an
andd no
nnon-randomized
n ra
nrand
ndom
nd
mizzed
d rregistries
eg
gis
i tr
t ies
e ooff LM patients,
pat
atieent
n s, mortality
mor
orta
t liity was
ta
was similar
similar in
randomized
both treatment groups at 5 years1,3,14-19. Only one propensity matched registry did find increased
mortality in LM patients treated with DES compared with CABG2.
Procedure-related stroke is a serious and well-known complication after CABG20. Stroke
was significantly increased in LM CABG-randomized patients at 1 year and remains
significantly increased at 5 years. The majority of strokes in the CABG arm occurred acutely
(<30d) whereas most occurred >30 days after the index procedure in the PCI arm. The
cumulative stroke curves for LM patients remain parallel after one year. This is different from
the observed stroke rate in the global SYNTAX population ( LM plus 3VD) where the stroke rate
8
DOI: 10.1161/CIRCULATIONAHA.113.006689
was significantly increase with CABG at one year and no more significant at 5 years21.
Significant increases in repeat revascularization were observed within 1 year after the
index procedure10,11. The rate of repeat revascularization in the LM PCI subgroup at 5 years
(26.7%) is consistent with other published randomized trials and registries comparing PCI and
CABG-treated LM patients (15.7% - 28.4%2,3,14-19 ; but was higher in the CABG LM cohort
(15.5%) compared with these studies (3.2% - 8.4%)2,3,14-19. In the patient population analyzed,
the increased likelihood of repeat revascularization with PCI is a trade-off; CABG has an
increased stroke rate2-7, 11. This difference in outcome between the 2 revascularization strategies
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
is important to highlight in patient discussions as the relative importance attributed to each varies.
Revascularization was also increased in LM patients with medically-trea
medically-treated
ateed di
diab
diabetes
abet
ab
etes
et
es
randomized
andomized to PCI compared to CABG; all other events including the composite MACCE seem
too bbee co
comp
comparable.
mpar
mp
a able
lee. T
This
his must be treated with caution
caut
utio
ut
i n due to the small
io
sma
m ll nnumber
ma
umber of patients (67
um
patients).
patiien
e ts). Excess
Exces
esss mortality
morttal
mort
alit
ityy has
it
has been
been observed
obse
bserveed in other
othher studies
sttud
udiies off ddiabetic
iabe
ia
beti
t c ppatients
atie
at
ieent
ntss wi
with
th complex
coomp
omplex
2,22,23
2,22
2,23
3
coronary
co
oro
rona
nary
na
ry disease,
dis
iseease
easee, but
but not
noot in the
the SYNTAX
SYN
YNT
TAX trial
triaal2,2
tr
.
year
ye
ars,
ar
s, M
ACCE
AC
E iin
n PC
PCII LM ppatients
atie
at
ieent
ntss wi
with
th lo
llow
w or m
oder
od
e at
atee disease
dissea
di
ease
s ccomplexity
se
ompl
om
p ex
pl
e ity (low
At 5ye
5years,
MACCE
moderate
and intermediate SYNTAX Scores) was similar to patients randomized to CABG. However, in
patients with high SYNTAX Scores (•33), MACCE was significantly increased in the PCI arm.
Increased coronary disease did not impact stroke rate in either arm, similar to the findings from a
large meta-analysis of acute (30 days) and mid-term (1 year) stroke between CABG and PCI20.
Updated LM revascularization guidelines have recently assigned a Class IIb recommendation to
PCI in patients with low/intermediate SYNTAX Scores (or a class IIa indication in selected
patients without coexisting MVD)24,25. Since the SYNTAX trial was designed in 2004 new
generations of stents have emerged and proven superior to the TAXUS Express stent.
9
DOI: 10.1161/CIRCULATIONAHA.113.006689
Additionally, adjunct medication and techniques have improved significantly and together with
the evolution of the stent design have reduced mortality. Surgical techniques have evolved as
well. The ongoing EXCEL (Evaluation of Xience Prime or Xience V Versus CABG for
Effectiveness of Left Main Revascularization) trial is enrolling LM patients with mild to
moderate anatomic complexity (SYNTAX score ”32) using a more contemporary stent and
current surgical techniques, and will shed more light on the issues of LM revascularization;
EXCEL will compare the 3-year primary composite end point of death, MI, and stroke in
patients treated with PCI with DES to CABG.
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Potentially, with a heart team available, triaging of patients to PCI or CABG will provide
formalized
optimal outcomes for the patient. SYNTAX has beenn credited as the trial that fo
orm
mal
a izzed tthe
he
Heart Team concept: a multi-disciplinary group of health care professionals who assess and
manage
mannage
ma
nage ppatients
atiien
at
ientss with
wit complex coronary artery ddisease
isease26,27. Recent
ise
nt updates
upd
pddat
atees to the 2010 European
Society
S
occiet
cie y of Cardiology
Carrdi
diol
olog
ogyy and
an
nd the
the European
Euro
Eu
r pean
ro
pean Ass
Association
sociattion ffor
or C
Cardio-Thoracic
ardi
d o--Th
di
Thor
oraacic S
Surgery
urge
ur
gery
ry
yG
Guidelines
uiideeli
line
nees for
28,29
8,2
29
29
Coronary
Revascularization
Co
oro
r na
nary
ry
yR
evas
ev
ascu
cula
cu
lari
riza
zaati
tioon2255, an
andd th
tthe
hee 20
2011
011 A
ACC
CC G
Guidelines
uiideeli
linnes
nes fo
fforr PC
PCII aand
ndd CA
CABG
B 28
BG
list
li
istt tthe
hee
as a class
clas
cl
asss 1 indication
as
in
ndi
d ca
c tiion for
for
o treatment
tre
reat
a me
at
mennt of coronary
cor
o on
onar
aryy ar
ar
arte
tery
te
ry ddisease.
isea
is
ease
ea
se.. A te
se
team
am-b
am
-b
bas
a ed
Heart Team as
artery
team-based
approach to patient care, especially in patients with complex disease or circumstances, will likely
further improve outcomes.
Study Limitations
Hierarchical primary endpoint testing of the SYNTAX study allowed testing of the LM subgroup
only if the overall comparison reached statistical significance. As non-inferiority of the primary
endpoint was not met, the results from this analysis must be considered hypothesis-generating
only and should be interpreted with care. The results may have been confounded by the
heterogeneity of the LM subgroup which consisted of LM patients with 0, 1, 2 or 3 vessel
10
DOI: 10.1161/CIRCULATIONAHA.113.006689
disease. Although the SYNTAX study was designed to follow patients for 5 years, additional
differences between the treatment arms may develop over time.
Conclusions
The SYNTAX trial is currently the largest RCT comparing PCI with CABG in complex coronary
disease with a prespecified and powered LM subgroup. CABG has been the gold standard for
revascularization of the LM vessel; however, this hypothesis-generating subanalysis of the
SYNTAX trial, suggests that PCI can provide equivalent long-term (to 5 years) death/stroke or
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
MI to CABG, in particular in the subset of LM subjects with SYNTAX Scores <33.
Corporation.
Funding Sources: The SYNTAX Study was supported by Boston Scientific Co
orp
por
orat
atio
at
io
on.
n
Conflict of Interest Disclosures: TEF received consulting and lecture fees (BSC, Abbott),
research
full-time
employees
esea
search
arch support
sup
pportt (BSC,
(BS
BSC,
C, Abbott)
Abb
bbottt) andd JH,
H KR
KR and
an
nd KD
KDD ar
aree al
aalll fu
ulll-t
-tim
me em
employ
oyee
ees of BSC
SC and
have
ownership
have
hav
ve stock own
wneersship inn BSC.
BSC. All
Alll other
oth
ther
er authors
auth
th
hors have
havve no
no disclosures
disc
di
sclo
losu
suures too declare.
dec
ecla
larre.
la
re.
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coronary intervention: Executive summary: A report of the American College of Cardiology
Foundation/American Heart Association Task Force on practice guidelines and the Society for
Cardiovascular Angiography and Interventions. Circulation. 2011;124:2574-2609.
14
DOI: 10.1161/CIRCULATIONAHA.113.006689
Table 1. Components of MACCE and Stent Thrombosis Incidence Rates at 5 Years in Left Main
Patients.
Event
PCI
(N=357)
CABG
(N=348)
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
MACCE
36.9% (130)
All Death/Stroke/MI
19.0% (67)
All Death
12.8% (45)
Cardiac Death
8.6% (30)
Stroke
1.5% (5)
MI
8.2% (28)
Revascularization
26.7% (90)
PCI
21.6% (73)
CABG
7.9% (26)
Stent Thrombosis/Graft Occlusion 5.1% ((17))
31.0% (103)
20.8% (69)
14.6% (48)
7.2% (23)
4.3% (14)
4.8% (16)
15.5% (49)
13.8% (43)
1.7% (6)
4.4% ((14))
Hazard Ratio
PCI vs CABG
[95% CI]
1.23 [0.95, 1.59]
0.91 [0.65, 1.27]
0.88 [0.58, 1.32]
1.23 [0.71, 2.11]
0.33 [0.12, 0.92]
1.67 [0.91, 3.10]
1.82 [1.28, 2.57]
1.67 [1.15, 2.43]
4.16 [1.71, 10.10]
1.15 [[0.57,, 2.33]]
P value
0.12
0.57
0.53
0.46
0.03
0.10
<0.001
0.007
<0.001
0.70
Values are given as Kaplan Meier event rate % (n) and calculated by time to event analyses withh lo
log
log-rank
g-ra
g-ra
rank
nk P values.
val
alue
ues.
thrombosis/graft
occlusion
Site-reported data. MACCE and its components are calculated post allocation; stent thrombosis/
/grrafft oc
occl
cluusio
cl
usio
ion
n ar
aaree
calculated
alculated post index procedure. Per-protocol stent thrombosis. CABG=coronary artery bypass graft
grafft surgery;
CVA=cerebrovascular event; MACCE=major adverse cardiovascular and cerebrovascular events; MI=myocardial
infarction;
nfarction; PCI=percutaneous coronary intervention.
15
DOI: 10.1161/CIRCULATIONAHA.113.006689
Table 2. Components of MACCE Rates at 5 Years in Left Main Patients Stratified by SYNTAX
Score Tercile.
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
SYNTAX Score 0-32
MACCE
All Death/Stroke/MI
All Death
Cardiac Death
Stroke
MI
Revascularization
PCI
CABG
SYNTAX Score •33
MACCE
All Death/Stroke/MI
All Death
Card
Ca
rdiaac De
rd
D
ath
Cardiac
Death
St ke
Stroke
MI
Revasccul
u arrizzatio
on
Revascularization
PCI
PCI
CABG
CABG
PCI
CABG
N=221
31.3% (68)
14.8% (32)
7.9% (17)
4.2% (9)
1.4% (3)
6.1% (13)
22.6% (48)
19.3% (41)
6.2% (13)
N=135
46.5% (62)
26.1% (35)
20.9% (28)
15.8% (21)
1.6%
1.
6% ((2)
2)
11
1.7
.7%
% (1
(15)
11.7%
344.11% (42)
(4
42)
34.1%
25.6
25
.6%
.6
% (3
(32)
2)
25.6%
11
( 3))
(1
11.2%
(13)
N=196
32.1% (60)
19.8% (37)
15.1% (28)
8.3% (15)
3.9% (7)
3.8% (7)
18.6% (33)
17.1% (30)
1.5% (3)
N=149
29.7% (43)
22.1% (32)
14.1% (20)
55.9%
. % (8)
.9
44.9%
.99% (7
(7))
66.1%
.11% (9
9)
(9)
111.66% (16)
(16)
11.6%
99.5%
.5
5% (1
(13)
3)
2.0%
% (3)
( )
(3
Hazard Ratio
PCI vs CABG
[95% CI]
P Value
0.94 [0.67, 1.33]
0.71 [0.44, 1.14]
0.50 [0.27, 0.91]
0.50 [0.22, 1.14]
0.35 [0.09, 1.35]
1.58 [0.63, 3.95]
1.23 [0.79, 1.91]
1.15 [0.72, 1.83]
3.68 [1.05, 12.91]
0.74
0.16
0.02
0.09
0.11
0.33
0.36
0.57
0.03
1.78 [1.21, 2.63
63
3]
2.63]
1.23 [0.76, 1.98]
1.59 [0.90, 2.83]
2.98
8 [[1.32,
1 32, 6.73]
1.
00.32
0.
.32
2 [[0.07,
0.07,, 1.
0.
1.54
54]]
1.54]
1.88
1.88
8 [0
0.82
2, 4.30
44.30]
.30
0]
[0.82,
3.30 [1.86,
[1
1.8
.866, 55.88]
.88]]
3.30
33.07
.077 [1
.0
1.6
.61,
1 55.85]
1,
. 5]
.8
[1.61,
5 01 [1.43,
5.
[1.43
43,, 17.57]
17.557]]
17
5.01
00.
.00
0033
00
0.003
0.40
0.11
0.006
0.13
13
0.13
0.13
<
0.00
001
00
<0.001
<
0.00
0.
0011
00
<0.001
00.005
.0005
Values are given
giv
ven
n as
as Kaplan
Kapl
Ka
plan
pl
an Meier
Meiier event
eveent rate
rat
atee % (n)
(n) and
and calculated
c lccul
ca
ulat
ated
at
e bbyy ti
time
me tto
o ev
eevent
entt an
en
anal
analyses
alys
al
yses
ys
e w
es
with
ithh lo
it
loglog-rank
g-ra
grank P values..
ra
Si
Site
te-rep
repor
orte
ted
d da
data
ta MA
MACC
CCE
E an
andd it
itss co
comp
mpon
onen
ents
ts aare
re ccalculated
alcu
al
cula
late
tedd post
post aallocation.
lloc
ll
ocat
atio
ionn C
ABG=
AB
G=co
coro
rona
nary
ry aartery
rter
rt
eryy by
bypa
pass
ss ggraft
raft
ra
ft
Site-reported
data.
MACCE
components
CABG=coronary
bypass
surgery; CVA=cerebrovascular event; MACCE=major adverse cardiovascular and cerebrovascular events;
MI=myocardial infarction; PCI=percutaneous coronary intervention.
Figure Legends:
Figure 1. Patient disposition in the prespecified LM subgroup of SYNTAX. *Patients who died
within the first were accounted for at 5 year follow up.
Figure 2. Five-year incidence of cardiac events in LM patients. Hazard ratio and 95%
confidence intervals are from Cox’s partial likelihood method. Event rates are Kaplan-Meier
16
DOI: 10.1161/CIRCULATIONAHA.113.006689
estimates with a log-rank P-value.
Figure 3. Five-year incidence of cardiac events in patients with A) low and intermediate (0-32)
and B) high (•33) SYNTAX Scores. Hazard ratio and 95% confidence intervals are from Cox’s
partial likelihood method. Event rates are Kaplan-Meier estimates with a log-rank P-value.
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
17
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Figure 1
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Figure 2
Downloaded from http://circ.ahajournals.org/ by guest on June 18, 2017
Figure 3
Five-Year Outcomes in Patients with Left Main Disease Treated with Either Percutaneous
Coronary Intervention or Coronary Artery Bypass Grafting in the SYNTAX Trial
Marie-Claude Morice, Patrick W. Serruys, A. Pieter Kappetein, Ted E. Feldman, Elisabeth Ståhle,
Antonio Colombo, Michael J. Mack, David R. Holmes, James W. Choi, Witold Ruzyllo, Grzegorz
Religa, Jian Huang, Kristine Roy, Keith D. Dawkins and Friedrich Mohr
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Circulation. published online April 3, 2014;
Circulation is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2014 American Heart Association, Inc. All rights reserved.
Print ISSN: 0009-7322. Online ISSN: 1524-4539
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://circ.ahajournals.org/content/early/2014/04/03/CIRCULATIONAHA.113.006689
Data Supplement (unedited) at:
http://circ.ahajournals.org/content/suppl/2014/04/03/CIRCULATIONAHA.113.006689.DC1
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published in
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Supplementary Table 1. Components of MACCE and Stent Thrombosis Incidence Rates at 5
Years in Left Main Patients with and without Diabetes
Event
DM
N-DM
PCI
CABG
PCI
CABG
(N=75)
(N=75)
(N=271)
(N=247)
49.3% (37/75)
40.0% (30/75)
34.3% (93/271)
30.0% (74/247)
22.7% (17/75)
30.7% (23/75)
18.5% (50/271)
19.0% (47/247)
18.7% (14/75)
18.7% (14/75)
11.4% (31/271)
14.2% (35/247)
Stroke
1.3% (1/75)
6.7% (5/75)
1.5% (4/271)
3.6% (9/247)
MI
8.0% (6/75)
9.3% (7/75)
8.1% (22/271)
3.6% (9/247)
37.3% (28/75)
17.3% (13/75)
22.9% (62/271)
14.6% (36/247)
30.7% (23/75)
13.3% (10/75)
18.5% (50/271)
13.4% (33/247)
8.0% (6/75)
4.0% (3/75)
7.4% (20/271)
1.2% (3/247)
6.7% (5/75)
6.7% (5/75)
4.4% (12/271)
3.6% (9/247)
Post-Allocation
MACCE
All Death/Stroke/MI
All Death
Revascularization
PCI
CABG
Post-Procedure Stent
Thrombosis/Graft
Occlusion
Values are given as % (n/N) and calculated binary analysis.