Download Revascularization for Unprotected Left Main Stem Coronary Artery

Journal of the American College of Cardiology
© 2008 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 51, No. 9, 2008
ISSN 0735-1097/08/$34.00
doi:10.1016/j.jacc.2007.09.067
STATE-OF-THE-ART PAPER AND COMMENTARY
Revascularization for Unprotected
Left Main Stem Coronary Artery Stenosis
Stenting or Surgery
David P. Taggart, MD (HONS), PHD, FRCS,* Sanjay Kaul, MD, FACC,†
William E. Boden, MD, FACC,‡ T. Bruce Ferguson, JR, MD, FACC,§
Robert A. Guyton, MD, FACC,¶ Michael J. Mack, MD,# Paul T. Sergeant, MD, PHD,††
Richard J. Shemin, MD, FACC,** Peter K. Smith, MD, FACC,储
Salim Yusuf, DPHIL, FRCPC, FRSC, FACC‡‡
Oxford, United Kingdom; Los Angeles, California; Buffalo, New York; Greenville and Durham,
North Carolina; Atlanta, Georgia; Dallas, Texas; Leuven, Belgium; and Hamilton, Ontario, Canada
For coronary artery disease with unprotected left main stem (LMS) stenosis, coronary artery bypass grafting
(CABG) is traditionally regarded as the “standard of care” because of its well-documented and durable survival
advantage. There is now an increasing trend to use drug-eluting stents for LMS stenosis rather than CABG despite very little high-quality data to inform clinical practice. We herein: 1) evaluate the current evidence in support of the use of percutaneous revascularization for unprotected LMS; 2) assess the underlying justification for
randomized controlled trials of stenting versus surgery for unprotected LMS; and 3) examine the optimum approach to informed consent. We conclude that CABG should indeed remain the preferred revascularization treatment in good surgical candidates with unprotected LMS stenosis. (J Am Coll Cardiol 2008;51:885–92) © 2008
by the American College of Cardiology Foundation
Percutaneous coronary intervention (PCI) is frequently
favored as an initial treatment strategy by some interventional cardiologists in patients with multivessel coronary
artery disease (CAD) despite evidence from a meta-analysis
of randomized trials (1) and registry data (2) favoring
coronary artery bypass grafting (CABG). Food and Drug
Administration approval of drug-eluting stents (DES) in
2003 has further encouraged this practice even in “off-label”
situations (3). Although DES do not improve survival or
reduce myocardial infarction in comparison with bare-metal
From the *Department of Cardiac Surgery, University of Oxford, John Radcliffe
Hospital, Oxford, United Kingdom; †Division of Cardiology, Cedars-Sinai Heart
Institute, Los Angeles, California; ‡Department of Cardiovascular Services, Kaleida
Health, Buffalo General and Millard Fillmore Hospitals, University at Buffalo School
of Medicine and Biomedical Sciences, Buffalo, New York; §Division of Cardiothoracic and Vascular Surgery, Brody School of Medicine, Eastern Carolina University,
Greenville, North Carolina; 储Division of Cardiothoracic Surgery, Duke University
Medical Center, Durham, North Carolina; ¶Division of Cardiothoracic Surgery,
Emory University School of Medicine, Atlanta, Georgia; #Cardiopulmonary Research Science Technology Institute, Medical City Hospital, Dallas, Texas; **Division
of Cardiothoracic Surgery, Department of Surgery, David Geffen School of Medicine
at UCLA, Cardiovascular Center, Los Angeles, California; ††Cardiac Surgery
Department, University Hospital Gasthuisberg, Leuven, Belgium; and the ‡‡Population Health Research Institute, McMaster University, Hamilton Health Sciences,
Heart and Stroke Foundation, Hamilton, Ontario, Canada.
Manuscript received July 3, 2007; revised manuscript received August 9, 2007,
accepted September 7, 2007.
stents (BMS) (4), and despite concerns about their lack of
cost-effectiveness (5) and increased risk of stent thrombosis
(6), enthusiasm for their use in the coronary arteries has now
encouraged some to advocate their use in left main stem
(LMS) stenosis, for which CABG is traditionally regarded
as the standard of care because of its well-documented and
durable survival advantage (7–9). Indeed, current American
College of Cardiology/American Heart Association (ACC/
AHA) guidelines state that for LMS stenosis PCI is a class
III indication (i.e., that the procedure is generally not effective
and may even be harmful) in those who are otherwise eligible
for CABG (10,11), and this view is echoed in the European
Society of Cardiology’s PCI guidelines, which state that
“stenting for unprotected left main disease should only be
considered in the absence of other revascularization options”
(12). Nevertheless, in a 2004 survey of interventions for LMS
stenosis, PCI was used in 29% of European and 18% of U.S.
patients (13). This practice has been justified on the short-term
follow-up of small cohorts of highly selected patients receiving
DES for LMS stenosis and has persuaded some interventionalists to question whether it is now actually time for DES to
replace CABG completely (14).
Although there is an important role for PCI in patients
with LMS stenosis who are hemodynamically unstable
or ineligible for CABG, this article reviews current
886
Taggart et al.
Stenting Versus Surgery for LM Stem Stenosis
Abbreviations
and Acronyms
ACC/AHA ⴝ American
College of Cardiology/
American Heart Association
BMS ⴝ bare-metal stent(s)
CABG ⴝ coronary artery
bypass grafting
CAD ⴝ coronary artery
disease
DES ⴝ drug-eluting stent(s)
IMA ⴝ internal mammary
artery
outcomes with percutaneous and
surgical revascularization to examine whether there is sufficient
clinical evidence to support the
use of stents in the majority of
elective patients with unprotected LMS (i.e., where there are
no existing bypass grafts).
Pathology of LMS
and Implications for
Revascularization With
Stents or Surgery
LMS ⴝ left main stem
A significant LMS stenosis is
considered to be a lesion occupying over 50% of the vessel diamPCI ⴝ percutaneous
eter. Left main stem stenosis curcoronary intervention
rently occurs in 4% to 6% of all
RCT ⴝ randomized
patients undergoing coronary ancontrolled trial
giography (15) and in 30% of
CABG patients (16).
Left main stem stenosis is theoretically an attractive
target for PCI because it is the most proximal component of
the left coronary circulation and because of its relatively
large diameter. However, in reality, 3 important anatomical
features carry important qualifications about the likely
success of PCI and CABG in LMS stenosis:
MACE ⴝ major adverse
coronary events
• Left main stem stenosis occurs as an isolated lesion in
only 6% to 9% of patients, whereas over 70% to 80% of
patients also have multivessel CAD (17–24), thereby
potentially enabling more complete coronary revascularization with CABG than with stenting.
• Most LMS stenoses (40% to 94%) occur in the distal
segment of the artery and extend into the proximal
coronary arteries (17–24); such bifurcated or trifurcated
lesions have a high risk of restenosis (25), while acute
occlusion at this site can have catastrophic consequences.
• Morphologically, around one-half of LMS lesions have
significant calcification (15).
Whereas considerations about the precise anatomical location and complexity of LMS stenosis impact critically on both
the short- and long-term outcomes of PCI, they have negligible influence on the success of CABG, as the distal anastomoses of the bypass grafts are to the mid or distal coronary
vasculature, well beyond all diseased segments in both the LM
and the proximal coronary arteries, thereby protecting entire
proximal zones of vulnerable myocardium.
Rationale for CABG as the “Standard
of Care” Treatment for LMS Stenosis
In 1975 Cohen and Gorlin (26) first reported that CABG
resulted in a significant improvement in 10-year survival
compared with medical therapy in patients with significant
JACC Vol. 51, No. 9, 2008
March 4, 2008:885–92
LMS stenosis, an observation confirmed in 3 randomized
trials (7) and numerous observational studies over the next 2
decades. Although both the medical therapy and surgical
techniques used in these studies are outdated by today’s
standards (e.g., aspirin, statins, and internal mammary
artery [IMA] grafts were not widely used), a meta-analysis
of these trials demonstrated a significant relative risk reduction in mortality with CABG of about 66% at 5 years with
the benefit extending to 10 years (7). Even so, the trials
probably substantially underestimated the real survival benefit of CABG surgery because the trial patients were
relatively low risk, only 10% of surgical patients received an
IMA graft (which leads to superior long-term graft patency
and a clear survival benefit), and analysis on an intentionto-treat basis “discounted” the survival advantage of CABG
in the 40% of the medical group who crossed over to surgery
(7). Indeed, in the largest prospective study of LMS
stenosis, in which 1,484 patients in the CASS (Coronary
Artery Surgery Study) registry were followed for up to 16
years, the overall median survival for CABG patients was
13.3 years versus 6.6 years for medical therapy (8). Since
these pivotal studies, improvements in medical therapy have
benefited both surgical and medical groups, but in view of
the overall survival advantage of CABG in most angiographic and clinical subsets, current ACC/AHA guidelines
state that “the benefit of surgery over medical treatment in
patients with significant LMS stenosis (greater than 50%) is
little argued” (9).
Current Results for CABG in LMS Stenosis
In the last decade, 6 groups from Europe and the U.S. have
reported CABG results in cohorts of at least 300 patients
with LMS stenosis (16,27–31) (Table 1). Cumulatively,
these studies included almost 11,000 patients of whom
around one-third (range 5% to 57%) underwent urgent
surgery with an average in-hospital mortality of 2.8% and
30-day mortality of 3% to 4.2% (Table 1). In the largest
individual study, the Society of Cardiothoracic Surgery in
the U.K. reported a mortality of 3% for all 5,003 patients
undergoing CABG for LMS stenosis in 2003 (compared
with ⬍2% in over 17,000 patients with no LMS stenosis)
(31). Two recent British studies reported excellent 2-year
survival rates of 94% and 95% (28,30). As for all cardiac
surgical procedures, the mortality rate is strongly influenced
by comorbidities; for example, Ellis et al. (27) reported that
3-year mortality for CABG in LMS stenosis varied from
4% in low-risk patients to 40% in those with significant and
multiple comorbidities (27).
Left main stem stenosis may also be particularly suitable
for the use of bilateral IMA grafts. The angiographic
patency of both IMA placed to left-sided coronary vessels is
over 95% at 1 week and at 7 years (32) and may translate
into a significant survival benefit. In a systematic review of
over 15,000 CABG patients matched for age, gender,
diabetes, and left ventricular function, the hazard ratio for
Taggart et al.
Stenting Versus Surgery for LM Stem Stenosis
JACC Vol. 51, No. 9, 2008
March 4, 2008:885–92
887
Current Results of CABG for LMS Stenosis
Table 1
Current Results of CABG for LMS Stenosis
Mortality (%)
Author (Ref. #) (Year)
Year of Surgery
n
Hospital
30-Day
1-Year
2-Year
Jonsson et al. (31) (2006)
1970 to 1999
1,888
2.7
—
—
—
Lu et al. (30) (2006) (2005)
1997 to 2003
1,197
2.8
3
5
6
2003
5,003
3
—
—
—
—
Keogh and Kinsman (16) (2003)
Dewey et al. (29) (2006) (2001)
1998 to 1999
728
—
4.2
—
Yeatman et al. (28) (2006) (2001)
1996 to 2000
387
2.4
—
—
5
Ellis et al. (27) (2006) (1998)
1990 to 1995
1,585
2.3
—
—
—
—
10,788
2.8
—
—
—
Weighted average
CABG ⫽ coronary artery bypass grafting; LMS ⫽ left main stem.
death was 0.81 (95% confidence interval 0.70 to 0.94) with
bilateral versus single IMA grafts (number needed to treat,
13 to 16) (32). In addition, the use of bilateral IMA grafts
appears safe; the ART (Arterial Revascularisation Trial)
study of bilateral versus single IMA grafts reported an
overall 30-day mortality of 1% in over 3,000 patients (33).
PCI With BMS for LMS
Initial attempts at PCI using simple balloon angioplasty in
LMS stenosis were soon abandoned because of a high rate
of procedural complications from elastic recoil and vessel
dissection (Table 2). However, the ability of BMS to
minimize these complications encouraged at least 8 studies
of BMS in LMS stenosis in over 1,100 patients between
1999 to 2003 (34 – 41). Interpretation of outcome is, however, hampered by the absence of data regarding: 1) the
actual proportion of all LMS stenosis patients undergoing
PCI rather than CABG who were ineligible for CABG
because of other significant comorbidity (therefore at high
risk for PCI) and/or nonsurgical preference; and 2) the
number of patients with significant distal LMS stenosis and
multivessel CAD.
Notwithstanding these limitations, as shown in Table 2,
the overall in-hospital mortality averaged 6% with further
immediate revascularization in 4% (range 0% to 20%). Most
worrying, however, was a 1- to 2-year mortality of 17%
(range 3% to 31%) and a repeat revascularization rate of 29%
(range 15% to 34%). However, several authors have also
reported more favorable results in “low-risk” patients
(younger patients, normal ventricular function, and predominantly ostial or midshaft lesions) with 1-year mortality
rates of 3.4% (in the Ultima registry) (36) to 7% (35) and a
3-year mortality of 7.4% (39). Even in these patients,
however, repeat revascularization rates were 28% to 32%.
Furthermore, the results of CABG would also be excellent
in such low-risk populations; for example, the 1-year mortality rate in the 504 CABG patients in the SoS (Stent or
Surgery) trial was 0.8% (42).
Indeed, the overall high late mortality and revascularization rates with BMS influenced the 2001 (10) and 2005 (11)
ACC/AHA guidelines to state that PCI was a class III
indication for virtually all LMS stenosis in those who are
otherwise eligible for CABG (11) and the European Society
of Cardiology guidelines to conclude that “stenting for
unprotected left main disease should only be considered in
the absence of other revascularization options” (12).
PCI With DES for LMS Stenosis
Although, in comparison with BMS, DES do not reduce
the risk of death or myocardial infarction in stable CAD
(4,6), their ability to reduce restenosis has encouraged their
use in LMS disease (Table 3). Although 7 different groups
Eight Studies of PCI Using BMS in LMS
Table 2
Eight Studies of PCI Using BMS in LMS
In-Hospital to 30-Day
Author (Ref. #)
% Eligible
Stent
Revascularization
Mortality
Keeley et al. (34)
1
54
—
100%
5%
20%
31%
15%
Silvestri et al. (35): high risk
1
47
—
100%
9%
—
11%
15%
Silvestri et al. (35): low risk
Sites
n
Mortality
1- to 2-Year Follow-Up
Revascularization
1
93
—
100%
0%
—
3%
21%
Tan et al. (36): all
25
279
—
85%
14%
—
24%
34%
Tan et al. (36): low risk
25
89
—
85%
3.4%
—
3.4%
31%
Black et al. (37)
1
92
—
100%
4%
—
6.5%
16%
Takagi et al. (38)
1
63
—
58%
0%
10%
16%
31%
Park et al. (39)
4
270
—
100%
0%
4%
7%
29%
Brueren et al. (40)
1
71
—
64%
1%
4%
10%
25%
Kelley et al. (41)
3
97
—
100%
9%
—
28%
20%
38
1,155
6%
3%
17%
29%
Weighted average
BMS ⫽ bare-metal stent; LMS ⫽ left main stem; PCI ⫽ percutaneous coronary angioplasty.
20
66
21%
JACC Vol. 51, No. 9, 2008
March 4, 2008:885–92
*Data from 2 reports by same group presenting latest data.
CAD ⫽ coronary artery disease; DES ⫽ drug-eluting stent; EF ⫽ ejection fraction; LMS ⫽ left main stem; MI ⫽ myocardial infarction; TLR ⫽ target lesion revascularization; TVR ⫽ target vessel revascularization.
14
20
13%
1.6
8.3
13.4
7
11
14
1
2.1%
6
4.5
3.2
2.4
52
100
80
3
Weighted average
17
94
599
Palmerini et al. (24)
?
11
85
6
5
0
0
18
0
6
0
60
76
100
6
116
Kim et al. (22)*
23
85
42
⬍12
6
7
20
1
3
4
6
12
0
0
0
9
0
2
51
52
?
66
60
82
20
42
50
107
Chieffo et al. (21)
Lee et al. (23)
9
42
96
9
38
2
10
9
6
8
0
⬎40
?
94
—
—
50
Price et al. (20)
6
67
85
8
6
2
6
4
0
0
14
18
12
0
0
4
4
0
10
41
57
37
85
72
42
25
13
52
130
Valgimigli et al. (19)*
De Lezo et al. (17)
MI
(%)
n
Author (Ref. #)
Table 3
DES in LMS
Ostial
Mid
Distal/
Bifurcation
CAD
(%)
EF
Death
(%)
30-Day
TLR
(%)
Follow-Up,
Months
Death
(%)
MI
(%)
TLR/TVR
(%)
Angiography When
(Months)
Angiography
(%)
Restenosis
(%)
Taggart et al.
Stenting Versus Surgery for LM Stem Stenosis
DES in LMS
888
have published results involving 599 patients between 2004
to 2006 (17–24), interpretation is limited by small individual patient numbers (50 to 130 per study), incomplete
angiographic assessment of restenosis (only 1 study reassesses all patients [20]), short duration of follow-up (mean
of 11 months), and lack of a control group in 4 studies
(thereby inviting interpretive biases). Furthermore, with the
exception of the Bologna registry (24), for studies of BMS
there is little data regarding what proportions of all LMS
stenosis patients underwent PCI rather than CABG or were
ineligible for CABG because of other comorbidity and/or
nonsurgical preference (and were, therefore, also at high risk
for PCI).
As shown in Table 3, considering that 42% to 94% of
patients had significant distal or bifurcation LMS stenosis and
37% to 100% also had significant CAD, the immediate results
are encouraging. The in-hospital mortality rate averaged 2.4%
(range 0% to 11%), the immediate repeat revascularization rate
was 2% (range 0% to 6%), and biochemical evidence of
myocardial infarction was 6% (range 0% to 9%). However, at a
mean follow-up of 11 months (range 6 to 18 months),
mortality had increased to 7% (range 0% to 14%) and repeat
revascularization to 13% (range from 2% to 38%).
One group has reported no deaths in 116 LMS patients
at 18 months of follow-up but restenosis in 13% of the 85%
of patients who underwent angiography at 6 months
(18,22). In contrast, in the only study with complete
angiographic follow-up, the rate of restenosis increased
from 34% at 3 months to 44% at 9 months (20). This
disparity in restenosis rates may not only reflect differences
in patient selection, interventional techniques, and completeness and timing of angiographic follow-up but, most
importantly, differences in the incidence of distal/
bifurcation LMS stenosis. The crucial importance of distal
LMS stenosis as a predictor of adverse outcomes has
recently been re-emphasized by Valgimigli et al. (25) who,
at a median of 18 months, reported a 3-fold increase in
major adverse coronary events (MACE) in distal LMS
stenosis (30%) compared with those without (11%). And
both Price et al. (20) and Palmerini et al. (24) warned that
as restenosis was frequently asymptomatic, it mandated
serial angiographic follow-up, a view reiterated by Baim et
al. (14) who cautioned, “Without that safety net, one would
expect an up-tick in late mortality events resulting from
unrecognized restenosis in this critical location” (14).
Clearly, such a strategy not only has significant cost implications but also still begs the question: in view of potential
late failure of DES, how long should such surveillance
angiography be continued?
In contrast, the use of DES in nonbifurcation (an
infrequent anatomical subset), unprotected LMS appears to
be safe and effective based on a recent multicenter retrospective registry of 147 patients that reported a restenosis
rate of ⬍1% at 6-month angiographic follow-up, a major
adverse clinical event rate of 7.4%, and a cumulative cardiac
mortality of 2.7% at a median follow-up of 886 days (43).
JACC Vol. 51, No. 9, 2008
March 4, 2008:885–92
Current Comparisons of
PCI and CABG for LMS Stenosis
To date only 1 randomized trial of PCI versus CABG has
been reported (44). The LEMANS (Study of Unprotected
Left Main Stenting Versus Bypass Surgery) trial was a
randomized trial of 52 PCI (35% with DES) and 53 CABG
patients of whom approximately 60% had distal LMS
stenosis, and of whom 75% of the CABG group and 60% of
the PCI group had 3-vessel coronary artery disease (p ⫽
0.08). Although, as expected, the CABG group had more
short-term complications within the first month after surgery, the primary outcome of MACE at 1 year was similar
in the 2 groups, as 15% of the PCI group required further
PCI or CABG. Furthermore, the fact that only 72% of the
CABG group received an internal mammary artery graft
despite its well established survival benefit raises questions
about the quality of the surgery in the LEMANS trial, as
use of this graft should approach 100% in contemporary
practice. Currently a larger randomized trial of DES versus
CABG for LMS stenosis (the SYNTAX [Synergy between
PCI and Taxus and Cardiac Surgery] trial) has now completed enrollment.
Only 2 groups have reported registry data in patients with
LMS stenosis undergoing CABG or PCI with DES (21,24)
with at least 1-year follow-up. In the Bologna registry of
311 patients with LMS stenosis, 68% were deemed suitable
for either PCI or CABG, 19% for CABG only, and 13% for
PCI only (24). At a median follow-up of 14 months, the
mortality was 12% in 154 CABG and 13% in 157 PCI
patients (but 3%, respectively, in low-risk patients). The
repeat revascularization rate was, respectively, 3% for
CABG and 26% for PCI. In an Italian registry of 249 LMS
patients, there was no difference in 1-year mortality after
adjustment for baseline characteristics in the 107 PCI and
142 CABG patients, who were significantly older (68 vs. 64
years) with a higher proportion of renal failure (8% vs. 2%)
(21). Again, however, repeat revascularization was 20% in
PCI versus 4% of CABG patients, probably reflecting the
fact that 87% of patients had bifurcation disease (21).
The lack of long term follow-up is a fundamental
limitation of all of these studies. The benefits of CABG
surgery compared with medical therapy emerges beyond 1
year, as perioperative mortality and morbidity in the CABG
group becomes offset by mortality from CAD in the medical
group. Hence, the apparent lack of difference at 1 year is not
reassuring and does not contradict the longer-term benefits
of CABG.
Stent Thrombosis With DES
If restenosis is the Achilles heel of BMS, then stent
thrombosis is a potentially important limitation of DES,
with impaired endothelialization and healing the most
important of several possible mechanisms (45). However,
whereas restenosis usually has a relatively benign clinical
Taggart et al.
Stenting Versus Surgery for LM Stem Stenosis
889
outcome (except possibly in the LMS), stent thrombosis is
associated with a 65% to 70% increased risk of myocardial
infarction and a mortality of 25% to 45% (6). This persistent
potentially prothrombotic substrate necessitates prolonged
dual antiplatelet medication with aspirin and clopidogrel for
at least a year (46), compared with 1 month with BMS.
The precise incidence of DES thrombosis is unknown. It
was initially reported to be around 0.5%, similar to BMS, in
the pre-approval pivotal trials of BMS versus DES (in
low-risk patient and lesion cohorts, which involved limited
follow-up of 9 to 12 months). A recent Food and Drug
Administration Circulatory Devices Panel concluded that
DES now account for around 80% of all stent use and that
nearly 60% of their use is in “off-label” situations where,
depending on the complexity of the patient and the lesion,
they were “associated with increased risks of both early and
late stent thrombosis, as well as death or myocardial
infarction” with an annual thrombosis risk estimated at
between 1% to 5% (3).
The ACC/AHA now recommend that a longer duration
of dual antiplatelet therapy with aspirin and clopidogrel
(perhaps indefinitely) is warranted to mitigate the increased
risk of late stent thrombosis despite the significant longterm bleeding complications (47) and high costs (46).
Cautions Regarding Trials of
Stents or Surgery in LMS Stenosis
The randomized controlled trial (RCT), considered the
most robust form of evidence-based medicine, is predicated
on the prerequisite of equipoise, defined as substantial
uncertainty regarding the relative benefits and risks of
competing treatment options. As the stakes for LMS
stenosis are much higher than for other forms of CAD,
there are 2 schools of thought regarding how justifiable are
the ongoing or proposed RCT of PCI versus CABG given
current knowledge.
Proponents argue that PCI already offers tangible shortterm advantages over CABG as it is less invasive, reduces
hospitalization duration, avoids the disability of surgical
recovery, and allows patients to subsequently have CABG if
necessary. As nearly one-third of LMS patients in Europe
and one-fifth in the U.S. may have already been treated with
DES (13) based only on underpowered, nonrandomized,
and potentially biased studies, they advocate RCT to settle
which is the better treatment, rather than allow the current
highly variable and potentially dangerous clinical practice.
They maintain that PCI should be prudently constrained
within the strictly controlled and monitored environment of
the RCT and argue that such RCT are essential if innovation is not to be stifled, thereby denying individual patients
and society as a whole potentially better therapies.
In contrast, opponents of such RCT for LMS stenosis
question if there is sufficient evidence of equipoise to
warrant these trials. They maintain that the fundamental
flaw of such trials is the lack of equipoise between the
890
Taggart et al.
Stenting Versus Surgery for LM Stem Stenosis
treatments because CABG has a well-documented survival
benefit of many years (7–9), and as stenting has no survival
advantage over medical therapy in stable CAD (48,49), it is
counterintuitive to believe or expect that it will do so in
LMS stenosis. They emphasize that BMS in LMS stenosis
were, after promising early results, abandoned because of
excess late mortality and high intervention rates and that as
DES do not improve clinical outcome over BMS in stable
CAD (4), it is unlikely they will do so in LMS stenosis.
Furthermore, they argue that the notion that “CABG can
always be performed later” is a false premise with inherent
risks. First, timely crossover to surgery may be precluded
because restenosis in this critical lesion is frequently asymptomatic and can be abrupt (20,24). Second, observational
studies of tens of thousands of patients with multivessel
CAD have consistently shown that PCI with stents, followed by crossover to CABG when necessary, resulted in
inferior survival compared with an initial strategy of CABG
(2). The opponents of RCT in LMS stenosis believe that
patients should be offered the documented survival benefit
of CABG (because in no other area of medicine would it be
considered ethically justifiable to conduct an RCT that
involved withholding a therapy with proven and substantial
benefits) and that many appropriately informed patients
would be unlikely to trade off substantial and long-term
benefits of CABG (especially in an era when the procedural
mortality and morbidity are relatively low) for a much less
certain outcome with PCI.
Although there are no easy answers to resolve this
dilemma at the current time, the results of the ongoing
SYNTAX study should help inform clinical practice and
guide the design of future trials. Ideally, such trials should:
• Be vetted through ethics committees and institutional
review boards that are fully informed about the totality of
evidence, including the clear benefits of CABG on
mortality in LMS stenosis and the lack of efficacy of PCI
in any situation in patients with stable CAD;
• Be powered adequately to evaluate the clinically relevant
hard end point of mortality and clinically important
differences to avoid a spurious conclusion that the 2
procedures are equivalent;
• Appreciate that early mortality and MACE initially
“disadvantage” surgery, as most of these outcome measurements occur in the perioperative period;
• Include long-term follow-up (at least 5 years), as benefits
of surgery accrue with time; and
• Maintain a registry of potentially eligible patients not
entered in the trials.
Finally, for the results to be generalizable, a broad
category of at-risk patients, typical of those encountered
in routine clinical practice, must be included if feasible or
completely described and studied in registries if excluded
from randomization. It is vital that registry analysis
includes risk adjustment, is published with the primary
trial report, and includes sufficient patient descriptors to
JACC Vol. 51, No. 9, 2008
March 4, 2008:885–92
permit extrapolation of the results in formulating clinical
judgment.
The Need for a Standardized
Multidisciplinary Team Approach
As for any condition where several therapeutic approaches
are possible, a multidisciplinary team is essential to
ensure the highest likelihood that the most balanced
advice and best treatment option are offered to patients
with LMS disease. A multidisciplinary team can ensure
that the patient understands that whereas short-term
outcomes with PCI may appear satisfactory, the results by
1 year are less favorable and that significant uncertainties
about its long-term reliability and durability mandate
surveillance angiography, which should be weighed
against the proven survival benefits of surgery. However,
this ideal standard of care may be at risk of gradually
being eroded by an increasing tendency of partisan
interests to solely decide and instigate treatment, with the
patient often being influenced into making a preordained “choice.” Framing information in the simplistic
format—“we can fix your blockage with this stent or we
can have the surgeon crack your chest”—while implying
that the 2 treatments are otherwise equally efficacious
may ensure patient compliance but undermines the concept of informed consent and indeed misinforms patients.
Conclusions
The fact that most patients with LMS stenosis have
bifurcation disease and simultaneous multivessel CAD
predicates against likely long-term success with PCI. Consequently, in the absence of contraindications to surgery,
CABG should remain the standard of care for most patients
with LMS stenosis because of its substantial survival advantage and freedom from repeat intervention. Percutaneous
coronary intervention may be a reasonable alternative in
those with isolated LMS stenosis not involving the bifurcation or those ineligible for CABG. However, PCI (with
or without stents of any type) has been shown not to
confer any survival advantage compared with medical
therapy in any category of patients with stable CAD, and
concerns remain over the risk of stent thrombosis with
DES, particularly when used in “off-label” situations.
Despite their inherent limitations, the results of ongoing
trials with randomized and registry cohorts evaluating
DES with CABG should provide evidence-based guidance in selecting the preferred form of treatment for
LMS stenosis in the future. Until then, consistent with
ACC/AHA (10,11) and European Society of Cardiology
guidelines (12) and as stated by Serruys et al. (19),
“CABG should remain the preferred revascularization
treatment in good surgical candidates with left main
coronary artery disease.”
JACC Vol. 51, No. 9, 2008
March 4, 2008:885–92
Acknowledgments
The authors wish to acknowledge the helpful advice and
suggestions of Dr. Gabriel Steg and Dr. William Wijns in
reviewing this manuscript and the invaluable administrative
assistance of Mr. Michael Kuby of the Society of Thoracic
Surgeons.
Reprint requests and correspondence: Prof. David P. Taggart,
Cardiovascular Surgery, University of Oxford, Department of
Cardiac Surgery, John Radcliffe Hospital, Oxford OX3 9DU,
United Kingdom. E-mail: [email protected].
REFERENCES
1. Hoffman SN, TenBrook JA, Wolf MP, Pauker SG, Salem DN, Wong
JB. A meta-analysis of randomized controlled trials comparing coronary artery bypass graft with percutaneous transluminal coronary
angioplasty: one- to eight-year outcomes. J Am Coll Cardiol 2003;41:
1293–304.
2. Hannan EL, Racz MJ, Walford G, et al. Long-term outcomes of
coronary-artery bypass grafting versus stent implantation. N Engl
J Med 2005;352:2174 – 83.
3. Farb A, Boam MS. Stent thrombosis redux—the FDA perspective.
N Engl J Med 2007;356:984 –7.
4. Kastrati A, Mehilli J, Pache J, et al. Analysis of 14 trials comparing
sirolimus-eluting stents with bare-metal stents. N Engl J Med 2007;
356:1030 –9.
5. Hill R, Bagust A, Bakhai A, Dickson R, et al. Coronary artery stents:
a rapid systematic review and economic evaluation. Health Technol
Assess 2004;8:1–242.
6. Tung R, Kaul S, Diamond GA, Shah PK. Narrative review: drugeluting stents for the management of restenosis: a critical appraisal of
the evidence. Ann Intern Med 2006;144:913–9.
7. Yusuf S, Zucker D, Peduzzi P, et al. Effect of coronary artery bypass
graft surgery on survival: overview of 10-year results from randomised
trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration. Lancet 1994;344:563–70.
8. Caracciolo EA, Davis KB, Sopko G, et al. Comparison of surgical and
medical group survival in patients with left main equivalent coronary
artery disease. Long-term CASS experience. Circulation 1995;91:
2335– 44.
9. Eagle KA, Guyton RA, Davidoff R, et al. ACC/AHA 2004 guideline
update for coronary artery bypass graft surgery: a report of the
American College of Cardiology/American Heart Association Task
Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Surgery). J Am Coll Cardiol
2004;44:e213–311.
10. Smith SC Jr., Dove JT, Jacobs AK, et al. ACC/AHA guidelines for
percutaneous coronary intervention (revision of the 1993 PTCA
guidelines)— executive summary: a report of the American College of
Cardiology/American Heart Association Task Force on Practice
Guidelines (Committee to Revise the 1993 Guidelines for Percutaneous Transluminal Coronary Angioplasty). J Am Coll Cardiol 2001;37:
2215–39.
11. Smith SC Jr., Feldman TE, Hirshfeld JW Jr., et al. ACC/AHA/SCAI
2005 guideline update for percutaneous coronary intervention—
summary article: a report of the American College of Cardiology/
American Heart Association Task Force on Practice Guidelines
(ACC/AHA/SCAI Writing Committee to Update the 2001 Guidelines for Percutaneous Coronary Intervention). J Am Coll Cardiol
2006;47:216 –35.
12. Silber S, Albertsson P, Aviles FF, et al., Task Force for Percutaneous
Coronary Interventions of the European Society of Cardiology.
Guidelines for percutaneous coronary interventions. Eur Heart J
2005;26:804 – 47.
13. Kappetein AP, Dawkins KD, Mohr FW, et al. Current percutaneous
coronary intervention and coronary artery bypass grafting practices for
three-vessel and left main coronary artery disease. Insights from the
SYNTAX run-in phase. Eur J Cardiothorac Surg 2006;29:486 –91.
Taggart et al.
Stenting Versus Surgery for LM Stem Stenosis
891
14. Baim DS, Mauri L, Cutlip DC. Drug-eluting stenting for unprotected
left main coronary artery disease: are we ready to replace bypass
surgery? J Am Coll Cardiol 2006;47:878 – 81.
15. Ragosta M, Dee S, Sarembock IJ, Lipson LC, Gimple LW, Powers
ER. Prevalence of unfavorable angiographic characteristics for percutaneous intervention in patients with unprotected left main coronary
artery disease. Catheter Cardiovasc Interv 2006;68:357– 62.
16. Keogh BE, Kinsman R. Fifth National Adult Cardiac Surgical
Database Report 2003. Dendrite Clinical Systems, United Kingdom:
2004.
17. De Lezo JS, Medina A, Pan M, et al. Rapamycin-eluting stents for the
treatment of unprotected left main coronary disease. Am Heart J
2004;148:481–5.
18. Park SJ, Kim YH, Lee BK, et al. Sirolimus-eluting stent implantation
for unprotected left main coronary artery stenosis: comparison with
bare metal stent implantation. J Am Coll Cardiol 2005;45:351– 6.
19. Valgimigli M, van Mieghem CA, Ong AT, et al. Short- and
long-term clinical outcome after drug-eluting stent implantation for
the percutaneous treatment of left main coronary artery disease:
(RESEARCH and T-SEARCH). Circulation 2005;111:1383–9.
20. Price MJ, Cristea E, Sawhney N, et al. Serial angiographic follow-up
of sirolimus-eluting stents for unprotected left main coronary artery
revascularization. J Am Coll Cardiol 2006;47:871–7.
21. Chieffo A, Morici N, Maisano F, et al. Percutaneous treatment with
drug-eluting stent implantation versus bypass surgery for unprotected
left main stenosis: a single-center experience. Circulation 2006;113:
2542–7.
22. Kim YH, Park SW, Hong MK, et al. Comparison of simple and
complex stenting techniques in the treatment of unprotected left main
coronary artery bifurcation stenosis. Am J Cardiol 2006;97:1597– 601.
23. Lee MS, Kapoor N, Jamal F, et al. Comparison of coronary artery
bypass surgery with percutaneous coronary intervention with drugeluting stents for unprotected left main coronary artery disease. J Am
Coll Cardiol 2006;47:864 –70.
24. Palmerini T, Marzocchi A, Marrozzini C, et al Comparison between
coronary angioplasty and coronary bypass surgery for the treatment of
unprotected left main coronary artery stenosis (the Bologna registry).
Am J Cardiol 2006;98:54 –9.
25. Valgimigli M, Malagutti P, Rodriguez-Granillo GA, et al. Distal left
main coronary disease is a major predictor of outcome in patients
undergoing percutaneous intervention in the drug-eluting stent era: an
integrated clinical and angiographic analysis based on the RESEARCH
and T-SEARCH registries. J Am Coll Cardiol 2006;47:1530 –7.
26. Cohen MV, Gorlin R. Main left coronary artery disease. Clinical
experience from 1964 –1974. Circulation 1975;52:275– 85.
27. Ellis SG, Hill CM, Lytle BW. Spectrum of surgical risk for left main
coronary stenoses: benchmark for potentially competing percutaneous
therapies. Am Heart J 1998;135:335– 8.
28. Yeatman M, Caputo M, Ascione R, Ciulli F, Angelini GD. Off-pump
coronary artery bypass surgery for critical left main stem disease: safety,
efficacy and outcome. Eur J Cardiothorac Surg 2001;19:239 – 44.
29. Dewey TM, Magee MJ, Edgerton JR, Mathison M, Tennison D,
Mack MJ. Off-pump bypass grafting is safe in patients with left main
coronary disease. Ann Thorac Surg 2001;72:788 –91.
30. Lu JC, Grayson AD, Pullan DM. On-pump versus off-pump surgical
revascularization for left main stem stenosis: risk adjusted outcomes.
Ann Thorac Surg 2005;80:136 – 42.
31. Jonsson A, Hammar N, Nordquist T, Ivert T. Left main coronary
artery stenosis no longer a risk factor for early and late death after
coronary artery bypass surgery—an experience covering three decades.
Eur J Cardiothorac Surg 2006;30:311–7.
32. Taggart DP, D’Amico R, Altman DG. Effect of arterial revascularisation on survival: a systematic review of studies comparing bilateral
and single internal mammary arteries. Lancet 2001;358:870 –5.
33. Taggart DP, Lees B, Gray A, et al., ART Investigators. Protocol for
the Arterial Revascularisation Trial (ART). A randomised trial to
compare survival following bilateral versus single internal mammary
grafting in coronary revascularisation [ISRCTN46552265]. Trials
2006;7:7.
34. Keeley EC, Aliabadi D, O’Neill WW, Safian RD. Immediate and
long-term results of elective and emergent percutaneous interventions
on protected and unprotected severely narrowed left main coronary
arteries. Am J Cardiol 1999;83:242– 6.
892
Taggart et al.
Stenting Versus Surgery for LM Stem Stenosis
35. Silvestri M, Barragan P, Sainsous J, et al. Unprotected left main
coronary artery stenting: immediate and medium-term outcomes of
140 elective procedures. J Am Coll Cardiol 2000;35:1543–50.
36. Tan WA, Tamai H, Park SJ, et al. Long-term clinical outcomes after
unprotected left main trunk percutaneous revascularization in 279
patients. Circulation 2001;104:1609 –14.
37. Black A, Cortina R, Bossi I, Choussat R, Fajadet J, Marco J. Unprotected
left main coronary artery stenting: correlates of midterm survival and
impact of patient selection. J Am Coll Cardiol 2001;37:832– 8.
38. Takagi T, Stankovic G, Finci L, et al. Results and long-term predictors of
adverse clinical events after elective percutaneous interventions on unprotected left main coronary artery. Circulation 2002;106:698 –702.
39. Park SJ, Park SW, Hong MK, et al. Long-term (three-year) outcomes
after stenting of unprotected left main coronary artery stenosis in
patients with normal left ventricular function. Am J Cardiol 2003;91:
12– 6.
40. Brueren BR, Ernst JM, Suttorp MJ, et al. Long term follow up after
elective percutaneous coronary intervention for unprotected nonbifurcational left main stenosis: is it time to change the guidelines?
Heart 2003;89:1336 –9.
41. Kelley MP, Klugherz BD, Hashemi SM, et al. One-year clinical
outcomes of protected and unprotected left main coronary artery
stenting. Eur Heart J 2003;24:1554 –9.
42. Zhang Z, Mahoney EM, Spertus JA, et al. The impact of age on
outcomes after coronary artery bypass surgery versus stent-assisted
JACC Vol. 51, No. 9, 2008
March 4, 2008:885–92
43.
44.
45.
46.
47.
48.
49.
percutaneous coronary intervention: one-year results from the Stent or
Surgery (SoS) trial. Am Heart J 2006;152:1153– 60.
Chieffo A, Park SJ, Valgimigli M, et al. Favorable long-term outcome
after drug-eluting stent implantation in nonbifurcation lesions that
involve unprotected left main coronary artery. A multicenter registry.
Circulation 2007;116:158 – 62.
Buszman PE, Kiesz SR, Bochenek A, et al. Acute and late outcomes
of unprotected left main stenting in comparison with surgical revascularization. J Am Coll Cardiol 2008;51:538 – 45.
Joner M, Finn AV, Farb A, et al. Pathology of drug-eluting stents in
humans: delayed healing and late thrombotic risk. J Am Coll Cardiol
2006;48:193–202.
Grines CL, Bonow RO, Casey DE Jr., et al. Prevention of premature
discontinuation of dual antiplatelet therapy in patients with coronary
artery stents. J Am Coll Cardiol 2007;49:734 –9.
Bhatt DL, Fox KA, Hacke W, et al., CHARISMA Investigators.
Clopidogrel and aspirin versus aspirin alone for the prevention of
atherothrombotic events. N Engl J Med 2006;354:1706 –17.
Katritsis DG, Ioannidis JP. Percutaneous coronary intervention versus
conservative therapy in nonacute coronary artery disease: a metaanalysis. Circulation 2005;111:2906 –12.
Boden WE, O’Rourke RA, Teo KK, et al., COURAGE Trial
Research Group. Optimal medical therapy with or without PCI for
stable coronary disease. N Engl J Med 2007;356:1503–16.