A meta-analysis of 3,773 patients treated with percutaneous coronary intervention or surgery for unprotected left main coronary artery stenosis.

Abstract

This study sought to understand the total weight of evidence regarding outcomes in coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in unprotected left main coronary artery (ULMCA) stenosis.
Following a diagnosis of significant ULMCA stenosis in an individual that is a candidate for surgery, CABG is recommended by the American College of Cardiology/American Heart Association guidelines, whereas PCI is not recommended (Class III).
Databases were searched for clinical studies that reported outcomes after PCI and CABG for the treatment of ULMCA stenosis. Ten studies were identified that included a total of 3,773 patients.
Meta-analysis showed that death, myocardial infarction, and stroke (major adverse cardiovascular or cerebrovascular events) were similar in the PCI- and CABG-treated patients at 1 year (odds ratio [OR]: 0.84 [95% confidence interval: 0.57 to 1.22]), 2 years (OR: 1.25 [95% CI: 0.81 to 1.94]), and 3 years (OR: 1.16 [95% CI: 0.68 to 1.98]). Target vessel revascularization was significantly higher in the PCI group at 1 year (OR: 4.36 [95% CI: 2.60 to 7.32]), 2 years (OR: 4.20 [95% CI: 2.21 to 7.97]), and 3 years (OR: 3.30 [95% CI: 0.96 to 11.33]). There was no difference in mortality in PCI- versus CABG-treated patients at 1 year (OR: 1.00 [95% CI: 0.70 to 1.41]), 2 years (OR: 1.27 [95% CI: 0.83 to 1.94]), and 3 years (OR: 1.11 [95% CI: 0.66 to 1.86]).
Our analysis reveals no difference in mortality or major adverse cardiovascular or cerebrovascular events, for up to 3 years, between PCI and CABG for the treatment of ULMCA stenosis. However, PCI patients had a significantly higher risk of target vessel revascularization. In selected patients with ULMCA stenosis, PCI is emerging as an acceptable option.

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doi:10.1016/j.jcin.2009.05.020
2009;2;739-747
J. Am. Coll. Cardiol. Intv.
Fontana, Saibal Kar, Prediman K. Shah, Robert E. Weiss, and Raj Makkar
Hursh Naik, Anthony J. White, Tarun Chakravarty, James Forrester, Gregory

Intervention or Surgery for Unprotected Left Main Coronary Artery Stenosis
A Meta-Analysis of 3,773 Patients Treated With Percutaneous Coronary
This information is current as of May 18, 2011
http://interventions.onlinejacc.org/cgi/content/full/2/8/739
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A Meta-Analysis of 3,773 Patients Treated
With Percutaneous Coronary Intervention
or Surgery for Unprotected Left Main
Coronary Artery Stenosis
Hursh Naik, MD,* Anthony J. White, MBBS, PHD,* Tarun Chakravarty, MD,*
James Forrester, MD,* Gregory Fontana, MD,* Saibal Kar, MD,* Prediman K. Shah, MD,*
Robert E. Weiss, PHD,† Raj Makkar, MD*
Los Angeles, California
Objectives This study sought to understand the total weight of evidence regarding outcomes in
coronary artery bypass grafting (CABG) versus percutaneous coronary intervention (PCI) in unpro-
tected left main coronary artery (ULMCA) stenosis.
Background Following a diagnosis of significant ULMCA stenosis in an individual that is a candidate
for surgery, CABG is recommended by the American College of Cardiology/American Heart Associa-
tion guidelines, whereas PCI is not recommended (Class III).
Methods Databases were searched for clinical studies that reported outcomes after PCI and CABG
for the treatment of ULMCA stenosis. Ten studies were identified that included a total of 3,773 patients.
Results Meta-analysis showed that death, myocardial infarction, and stroke (major adverse cardio-
vascular or cerebrovascular events) were similar in the PCI- and CABG-treated patients at 1 year
(odds ratio [OR]: 0.84 [95% confidence interval: 0.57 to 1.22]), 2 years (OR: 1.25 [95% CI: 0.81 to
1.94]), and 3 years (OR: 1.16 [95% CI: 0.68 to 1.98]). Target vessel revascularization was significantly
higher in the PCI group at 1 year (OR: 4.36 [95% CI: 2.60 to 7.32]), 2 years (OR: 4.20 [95% CI: 2.21 to
7.97]), and 3 years (OR: 3.30 [95% CI: 0.96 to 11.33]). There was no difference in mortality in PCI-
versus CABG-treated patients at 1 year (OR: 1.00 [95% CI: 0.70 to 1.41]), 2 years (OR: 1.27 [95% CI:
0.83 to 1.94]), and 3 years (OR: 1.11 [95% CI: 0.66 to 1.86]).
Conclusions Our analysis reveals no difference in mortality or major adverse cardiovascular or cere-
brovascular events, for up to 3 years, between PCI and CABG for the treatment of ULMCA stenosis.
However, PCI patients had a significantly higher risk of target vessel revascularization. In selected
patients with ULMCA stenosis, PCI is emerging as an acceptable option.
2009;2:739–47) © 2009 by the American College of Cardiology Foundation
(J Am Coll Cardiol Intv
From *Cedars-Sinai Heart Institute, Cedars Sinai Medical Center, and †Department of Biostatistics, University of California,
Los Angeles School of Public Health, Los Angeles, California.
Manuscript received February 20, 2009; revised manuscript received April 30, 2009, accepted May 7, 2009.
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Significant left main stenosis is found in approximately 4% of
patients undergoing diagnostic coronary angiography (1) and
has been shown to portend high mortality (2–6). Trials
comparing coronary artery bypass grafting (CABG) to medical
therapy have shown a mortality reduction in patients with
these lesions (7–9). A meta-analysis of all available trials has
solidified CABG as the gold standard for the treatment of
unprotected left main disease (9). According to published
guidelines, it is a class I indication to perform CABG for
significant unprotected left main coronary artery (ULMCA)
stenosis in patients that are suitable for surgery (10).
Since these original trials were published, percutaneous
coronary intervention (PCI) has emerged as an alternative to
CABG for the treatment of coronary artery disease. Still, in
patients that are CABG candidates, PCI is designated a
Class III indication (10) and is a class IIa indication in
unsuitable candidates for CABG (11).
Advances in PCI technology and technique have led
some interventionalists to operate outside these guidelines.
In fact, a recent meta-analysis of
reports of unprotected left main
stenting demonstrated reason-
able outcomes (12), leading to
the conclusion that left main
stenting is at least feasible.
But how does PCI compare
with CABG? Although some
centers have published matched
data (13,14) a meta-analysis is
important because single-center
studies are typically underpow-
ered to detect differences in
mortality. To understand the
risk in unprotected left main pa-
tients, we performed a meta-
analysis of all available PCI versus CABG studies.
Methods
Search strategy. The meta-analysis considered studies that
compared PCI with CABG for unprotected left main
stenosis.
Candidate studies were identified by searching BioMed
Central, ClinicalTrials.gov, Google Scholar, and PubMed
and presentations of any randomized datasets at the major
meetings of the American Heart Association, the American
College of Cardiology, and Trans-Catheter Therapeutics.
All searches covered the period January 2004 through
December 2008. Key words used included “unprotected left
main,” “PCI,” “CABG,” and “comparison.” We also pe-
rused the bibliographies of retrieved articles and relevant
reviews to identify further relevant studies.
Studies were included if they met the following criteria: 1)
unrestricted comparison of cohorts of CABG and PCI for the
treatment of ULMCA stenosis; 2) a minimum of 1-year
follow-up; 3) documentation of survival and major adverse
cardiac and cerebrovascular events (MACCE); 4) more than
30 patients in each cohort along with reporting of risk scores;
5) publication in a peer-reviewed journal, or presentation of
randomized datasets at a major national cardiology meeting.
Outcomes. The primary end point was the odds ratio for
mortality after PCI or CABG, up to 3 years. Secondary end
points were the odds ratio of MACCE (death, myocardial
infarction [MI], and stroke) and target vessel revasculariza-
tion (TVR) after the procedure.
Data. From each study, we extracted patient characteristics,
study design, and outcomes at each of years 1, 2, and 3 after
treatment of ULMCA stenosis. When possible, actual
probabilities of mortality and death after 1, 2, or 3 years
following PCI or CABG were used to calculate odds ratios
(14–20). Alternatively, probabilities of mortality or
MACCE were estimated from published Kaplan-Meier
survival curves (13,21,22). Sample sizes at risk at each year
were taken from the reports, or in 1 case (18), estimated
using reported CABG/PCI group-specific means and vari-
ances of follow-up times and a log-normal model for actual
sample at risk (18). We reanalyzed our own dataset to
establish Kaplan-Meier curves and probabilities of mortality
and MACCE, which were used to calculate odds ratios
(14). We did not include adjusted odds ratios as only 1 study
reported this data (15), and only 4 others reported hazard
ratios (13,14,17,21). When possible, we also extracted TVR
from the total MACCE events and reported this outcome
as a separate measure. When MACCE was reported, all but
1 report defined MACCE to include death, MI, stroke, and
TVR. One report did not include stroke, and we did not
include this in our MACCE analysis (21). Another dataset
did not report total MACCE (17). The data from our
institution was reanalyzed up to September 2008 (14).
Statistical analysis. Each study is summarized by the odds
ratio (OR) for CABG against PCI. The ORs were com-
bined across studies using DerSimonian-Laird random
effects model and were pre-specified (23,24). We also
combined odds ratios with the fixed effects model using the
Mantel-Haenszel model. We performed the Woolf’s test
for heterogeneity. Sensitivity analyses were performed omit-
ting a single study at a time. Analysis was conducted in R (R
Development Core Team 2007) package rmeta version
2.14. All p values were 2-tailed and p ? 0.05 was considered
significant (25).
Results
Characteristics of the included studies. We identified 13
eligible studies (13–22,26–28) that compared PCI and
CABG cohorts for the treatment of ULMCA coronary
stenosis. Three of these studies were excluded because of: 1)
probable overlap with the institution’s previous report (27);
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Abbreviations
and Acronyms
CABG ? coronary artery
bypass grafting
MACCE ? major adverse
cardiac and cerebrovascular
events
MI ? myocardial infarction
OR ? odds ratio
PCI ? percutaneous
coronary intervention
TVR ? target vessel
revascularization
ULMCA ? unprotected left
main coronary artery
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2) subgroup analysis (27,28); and 3) ?30 PCI patients were
studied (26). Figure 1 demonstrates our search process.
Characteristics of each study are shown in Table 1. A total
of 3,773 patients were studied with 2,114 receiving CABG
and 1,659 receiving PCI. There were 354 PCI patients who
underwent bare-metal stent implantation and 1,305 PCI
patients who underwent drug-eluting stent implantation.
Of the total, 3,325 had more than 1 year of follow-up. The
overall internal validity was moderate and is illustrated in
Table 2. Of the 10 studies, 3 matched the treatment cohorts
using EuroSCORE (15,18,22), 2 randomized patients to
treatment group (16,20), and 3 used propensity scores to
Non-relevant studies
(n = 6975)
Articles requiring full
text/abstract review (n = 320)
Excluded (n = 310)
1. Lack of comparison of
PCI/CABG cohorts -307
2. < 30 patients included -1
3. Subgroup analysis of
left main patients -2
Articles meeting inclusion
criterion(n = 10)
Pub Med
Google
Scholar
Bio Med
Central
Clinical
Trials.gov
ACC/AHA/
TCT
Studies reviewed (n = 7294)
Figure 1. Search Process Algorithm
Flow chart demonstrating the resulting 10 studies that were analyzed. Subgroups of left main patients were not included due to the possibility of added con-
founding. ACC ? American College of Cardiology; AHA ? American Heart Association; CABG ? coronary artery bypass grafting; PCI ? percutaneous coronary
intervention; TCT ? Trans-Catheter Therapeutics.
Table 1. Study Characteristics
Study (Ref. #)CABG, nLIMA to LAD, %PCI, n DES, % BMS, %Unadjusted Risk
Method of
Adjustment Years
Brener et al. (18) 190 9997 5738 Matched on EuroSCOREUnneeded 1997–2006
Buszman et al. (16)5381 5235 65 Randomized, same riskUnneeded 2001–2004
Chieffo et al. (15)142 NA107 1000CABG slightly higherPropensity score
adjusted
2002–2004
Makikallio, et al. (19)238NA49 1000PCI group with a significantly
higher EuroSCORE
(7.7 vs. 5.2)
Unmatched,
unadjusted
2005–2007
Palmerini et al. (21) 15494.215760 40PCI higher. PCI group had a
significantly higher
Parsonett score
(17% vs. 13%)
Propensity score
adjusted
2002–2005
Sanmartin et al. (22) 24598 96 1000CABG slightly higherPropensity score
adjusted
2000–2005
SYNTAX left main* (20) 348NA 3571000Randomized, same riskUnneeded2006–2008
Seung et al. (13) 542“Whenever possible”542 7525Propensity score matchedUnneeded 2000–2006
White et al.† (14)6796.4671000Propensity score matchedUnneeded2003–2007
Wu et al. (17)135NA1354159Propensity score matchedUnneeded2000–2004
Total2,114 1,659
*Left main subset of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial. †Our data updated to October 2008.
BMS?bare-metalstent(s);CABG?coronaryarterybypassgrafting;DES?drug-elutingstent(s);LAD?leftanteriordescending;LIMA?leftinternalmammaryartery;PCI?percutaneouscoronaryintervention.
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guarantee like-to-like comparisons (13,14,17). We also
included the left main subset from the recently concluded
SYNTAX (Synergy Between Percutaneous Coronary Inter-
vention With Taxus and Cardiac Surgery) trial (20). In 2
studies (19,21), the baseline characteristics of the groups
were different. One of these studies (21) used the propensity
score to adjust for this difference. In these studies, the PCI
group had higher risk characteristics than the CABG group
as evidenced by a significantly higher Parsonnet (29) score
or EuroSCORE value (30).
Outcome
Death. The OR of the risk of death in the PCI group
compared with the CABG group in each study, at the 1-,
2-, and 3-year time points, is reported in Table 3. There
was no evidence for heterogeneity of treatment effect
among the studies for death at the 1-, 2-, or 3-year time
points.
The overall OR (95% confidence interval) of mortality
showed no difference between PCI and CABG at 1 year
(OR: 1.00 [0.70 to 1.41]), at 2 years (OR: 1.27 [0.83 to
1.94]), at 3 years (OR: 1.11 [0.66 to 1.86]) (Table 3 and
Figure 2).
MACCE. Table 4 and Figure 3 summarize MACCE without
TVR, for each study for PCI and CABG patients, at the 1-,
2-, and 3-year time points. Table 5 and Figure 4 summarize
the TVR results. Meta-analysis did not detect a difference in
MACCE, excluding TVR (death, MI, and stroke), in PCI-
versus CABG-treated patients at 1 year (OR: 0.84 [0.57 to
Table 2. Internal Validity
Study (Ref. #)
Prospective
Design
Multicenter
Enrollment
Selection
Bias
Performance
Bias
Attrition
Bias
Detection
Bias
Multivariate Adjustment for
Potential Confounders
Brener et al. (18)NoNoBBDB Probably adequate
Buszman et al. (16) Yes YesABABProbably adequate
Chieffo et al. (15)NoNoABABProbably adequate
Makikallio et al. (19) NoNoCBDB Probably adequate
Palmerini et al. (21)Yes NoABAB Probably adequate
Sanmartin et al. (22) No NoABABProbably adequate
SYNTAX left main* (20)Yes YesABABProbably adequate
Seung et al. (13)Yes YesABABProbably adequate
White et al.† (14)No NoABAB Probably adequate
Wu et al. (17)NoNoBBDBProbably adequate
Thiswasperformedby3independentreviewers.Theoverallbiasofthecombinedstudieswasconsideredmoderate.*LeftmainsubsetoftheSYNTAX(SynergyBetweenPercutaneousCoronaryIntervention
With Taxus and Cardiac Surgery) trial. †Our data updated to October 2008.
A ? risk of bias is low; B ? risk of bias is moderate; C ? risk of bias is high; D ? incomplete reporting.
Table 3. Estimated OR of Death in the PCI Group Versus the CABG Group at Each Year
Study (Ref. #)
Year 1
OR (95% CI)
Year 2
OR (95% CI)
Year 3
OR (95% CI)
Brener et al. (18)0.88 (0.26–2.99)1.08 (0.38–3.1)1.42 (0.56–3.63)
Buszman et al. (16)0.24 (0.03–2.23)
Chieffo et al. (15)0.43 (0.11–1.61)
Makikallio et al. (19)0.36 (0.08–1.58)
Palmerini et al. (21)0.27 (0.53–3.02)1.10 (0.29–4.2)
Sanmartin et al. (22)0.71 (0.20–2.53)0.93 (0.22–3.97)0.81 (0.07–9.35)
SYNTAX left main* (20)0.97 (0.47–2.02)
Seung et al. (13)1.13 (0.58–2.19)1.17 (0.65–2.12)1.01 (0.54–1.92)
White et al.† (14)1.36 (0.33–5.55)1.62 (0.15–17.05)
Wu et al. (17)3.06 (0.99–9.45)3.50 (0.89–13.80)
Summary (random effects)1.00 (0.70–1.41) 1.27 (0.83–1.94)1.11 (0.66–1.86)
Summary (fixed effects)0.97 (0.71–1.33)1.28 (0.84–1.94)1.11 (0.66–1.85)
Test for heterogeneitychi-square (9) ? 9.67, p ? 0.38chi-square (5) ? 2.52, p ? 0.77chi-square (2) ? 0.41, p ? 0.81
Est RE Var ? 0.02Est RE Var ? 0.0Est RE Var ? 0.0
Both fixed effects and random effects analysis were performed. *Left main subset of the SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) trial. †Our data
updated to October 2008. The chi-square test and p value are for the Woolf test of heterogeneity.
CI ? confidence interval; Est RE Var ? estimated random effects variance; OR ? odds ratio; other abbreviations as in Table 1.
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1.22], 2 years (OR: 1.25 [0.81 to 1.94], or at 3 years (OR: 1.16
[0.68to1.98]).Therewasastatisticallysignificantdifferencein
TVR favoring CABG at year 1 (OR: 4.36 [2.60 to 7.32]) and
year 2 (OR: 4.20 [2.21 to 7.97]). The effect was borderline not
significant in year 3 (OR: 3.30 [0.96 to 11.33]).
We were not able to separate TVR data from MACCE
from the study by Brener et al. (18), so this study did not
contribute to this MACCE meta-analysis. Also, the study by
Palmerini et al. (21) did not report stroke and thus we did not
include this set in our MACCE (death, MI, and stroke)
analysis.
There was no evidence of interstudy heterogeneity of treat-
ment effect for years 1, 2, and 3 for death, MI, and stroke (year
1: chi-square test: 9.96, p ? 0.18, estimated random effects
variance: 0.08; year 2: chi-square test: 0.71, p ? 0.7, estimated
random effects variance: 0; year 3: chi-square test: 1.47,
p ? 0.48, estimated variance: 0). There also was no evidence of
interstudy heterogeneity for TVR only (year 1: chi-square test:
13.28, p ? 0.66, estimated random effects variance: 0; year 2:
chi-square test: 3.69, p ? 0.30, estimated random effects
variance:0.09;year3:chi-squaretest:3.53,p?0.55,estimated
random effects variance: 0).
Discussion
The most important finding in our meta-analysis of left
main stenting versus CABG is that in a real-world appli-
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Brener
Buszman
Chieffo
Mäkikallio
Palmerini
Sanmartin
Seung
SYNTAX_LM
White
Wu
Summary
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
Mortality
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
.05.1
PCI better CABG better
.2.5125 1020
Figure 2. Odds Ratio of Mortality Following Treatment for ULMCA Disease in
PCI Versus CABG Patients
Odds ratio of mortality (with confidence intervals) following treatment for
unprotected left main coronary artery (ULMCA) disease after 1, 2, and 3 years.
Year 1: 1,393 PCI patients and 1,932 CABG patients; year 2: 528 PCI patients
and 890 CABG patients; and year 3: 263 PCI patients and 578 CABG patients.
Abbreviations as in Figure 1.
Buszman
Chieffo
Mäkikallio
Sanmartin
Seung
SYNTAX_LM
White
Summary
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
1
2
3
MACCEYear
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
●
.1
PCI better CABG better
.2.51251020
Figure 3. Odds Ratio of MACCE in PCI Versus CABG Patients
Odds ratio of major adverse cardiac and cerebrovascular events (MACCE)
(death, myocardial infarction, and stroke) in PCI patients versus CABG
patients after 1, 2, and 3 years. Year 1: 1,239 PCI patients and 1,614 CABG
patients; year 2: 432 PCI patients and 652 CABG patients; and year 3: 236
PCI patients and 451 CABG patients. Abbreviations as in Figure 1.
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cation among ?3,000 patients, there was no difference in
mortality between the 2 treatment options at 1, 2, or 3 years
of follow-up. In addition to the absence of difference in
mortality, we also found that the combined end point of
death, MI, and stroke was similar in the 2 treatment groups.
Of additional note is that 79% of the PCI patients received
drug-eluting stents, without succumbing to a higher mor-
tality than in patients treated with CABG. This is despite
the recent controversy involving stent thrombosis (31).
In contrast to the mortality, MI, and stroke results, TVR
was significantly higher in the PCI group. This result is
consistent with all comparisons of PCI to CABG and
reflects the restenosis rate associated with PCI (32). The
difference might be influenced by the 21% of patients with
bare-metal stents in the meta-analysis population, given
that bare-metal stent implantation has higher TVR rates in
large datasets (33). Regardless, it is clear from this analysis
that even with drug-eluting stents, there is a statistically
higher TVR rate.
Takagi et al. (34) recently presented a meta-analysis of
PCI versus CABG in unprotected left main patients. This
study identified only 6 studies. One study (35) included old
data from our group, of which we have presented updated
data here (14). Two of the studies (21,27) likely represent
overlapping data. Finally, their data does not include the
patients from 2 other studies (17,19) and the recently
presented randomized left main subset of the SYNTAX
trial (20). Given these reasons, we feel our analysis is more
inclusive of the data that is currently available.
The idea that PCI treatment of left main disease, as
compared with CABG, impedes treatment of moderate
proximal lesions and thereby increases risk was not borne
out in our data up to 3 years. Thus, the equivalence in death,
MI, and stroke along with a higher rate of TVR with PCI
Table 4. Estimated OR of Death, MI, and Stroke in the PCI Group Versus the CABG Group at Each Year
Study (Ref. #)
Year 1
OR (95% CI)
Year 2
OR (95% CI)
Year 3
OR (95% CI)
Buszman et al. (16)1.37 (0.58–3.23)
Chieffo et al. (15)0.53 (0.18–1.56)
Makikallio et al. (19)0.31 (0.09–1.06)
Sanmartin et al. (22) 0.48 (0.18–1.30)1.05 (0.33–3.30) 1.24 (0.21–7.31)
SYNTAX left main* (20)0.74 (0.43–1.28)
Seung et al. (13) 1.02 (0.57–1.84)1.16 (0.67–2.00)1.01 (0.56–1.84)
White et al.† (14)1.70 (0.73–3.97)1.81 (0.68–4.82) 2.82 (0.60–13.27)
Summary (random effects)0.84 (0.57–1.22)1.25 (0.81–1.94)1.16 (0.68–1.98)
Summary (fixed effects)0.82 (0.62–1.09)1.25 (0.81–1.94)1.16 (0.68–1.96)
Test for heterogeneitychi-square (6) ? 9.67, p ? 0.18chi-square (2) ? 0.71, p ? 0.70 chi-square (2) ? 1.47, p ? 0.48
Est RE Var ? 0.08Est RE Var ? 0.0 Est RE Var ? 0.0
Bothfixedeffectsandrandomeffectsanalysiswereperformed.*LeftmainsubsetoftheSYNTAXtrial.†OurdataupdatedtoOctober2008.Thechi-squaretestandpvaluearefortheWoolftestofheterogeneity.
MI ? myocardial infarction; other abbreviations as in Tables 1 and 3.
Table 5. Estimated OR of TVR in the PCI Group Versus the CABG Group at Each Year
Study (Ref. #)
Year 1
OR (95% CI)
Year 2
OR (95% CI)
Year 3
OR (95% CI)
Buszman et al. (16) 3.89 (1.30–11.68)
Chieffo et al. (15)6.69 (2.43–18.40)
Makikallio et al. (19)2.49 (0.44–13.99)
Sanmartin et al. (22)6.68 (1.27–35.02) 3.87 (0.75–19.88)5.89 (0.57–60.59)
SYNTAX left main* (20)1.94 (1.14–3.29)
Seung et al. (13)6.49 (2.96–14.23) 5.13 (2.50–10.54)5.40 (2.37–12.31)
White et al.† (14)3.10 (0.85–11.34) 1.55 (0.44–5.51)0.71 (0.10–5.16)
Wu et al. (17)13.77 (3.46–54.82)8.85 (2.08–37.65)
Summary (random effects)4.36 (2.60–7.32)4.20 (2.21–7.97)3.30 (0.96–11.33)
Summary (fixed effects)3.84 (2.77–5.33)4.35 (2.54–7.44)4.01 (2.01–7.98)
Test for heterogeneitychi-square (9) ? 9.67, p ? 0.38chi-square (9) ? 9.67, p ? 0.38chi-square (9) ? 9.67, p ? 0.38
Est RE Var ? 0.02Est RE Var ? 0.02 Est RE Var ? 0.02
Bothfixedeffectsandrandomeffectsanalysiswereperformed.*LeftmainsubsetoftheSYNTAXtrial.†OurdataupdatedtoOctober2008.Thechi-squaretestandpvaluearefortheWoolftestofheterogeneity.
TVR ? target vessel revascularization; other abbreviations as in Tables 1 and 3.
J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 2 , N O . 8 , 2 0 0 9
A U G U S T 2 0 0 9 : 7 3 9 – 4 7
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suggests that the choice between the 2 treatment options
can be defined by both the individual clinical presentation
and the practical tradeoff between differences in recovery
period and repeat revascularization.
The details of our meta-analysis also deserve iteration.
We only analyzed datasets that compared left main stenting
to a cohort of CABG for left main disease. In 2 of the 10
datasets (19,21) we used, substantially higher risk PCI
patients were compared with lower risk CABG. The other
8 datasets compared matched groups, which suggests that
the operators in these programs felt that left main PCI does
not portend worse outcomes. This view, different from the
guidelines, may reflect the influence of a number of recently
published datasets (12,36,37) reporting favorable outcomes
in left main PCI, even though most of these reports do not
compare PCI and CABG outcomes. One study (17), a New
York state data registry, reported results that differed from
the other 9 studies and from the conclusions of the
meta-analysis. The difference may be due to the inclusion of
data from many laboratories in the New York registry, as
opposed to the single high-volume centers represented in
other reports. Inclusion of this dataset makes our meta-
analysis less susceptible to publication bias given the mark-
edly different results reported.
We included in our analysis data from the recently
completed SYNTAX trial (20). This trial contains the
largest dataset to date comparing left main PCI and CABG.
This data has not been analyzed fully given that it was a
subset within the context of a larger group of patients
(multivessel disease and left main stenosis patients). The
study was not powered to detect statistically significant
differences between these groups. However we can make
inferences by including this data in a meta-analysis. Also,
our test of heterogeneity did not detect much difference
between studies, suggesting that the SYNTAX trial (20)
and LEMANS (Study of Unprotected Left Main Stenting
Versus Bypass Surgery) trial (16) (the only 2 randomized
datasets) reflect the real-world data described in the other
datasets. The absence of difference supports the notion that
real-world data is consistent with current randomized trials
for this particular analysis.
Although this meta-analysis represents ?3,000 patients
with general consistency between randomized and retro-
spective patients, the choice of therapy may best be deter-
mined by factors specific to the individual patient and
operator experience. The SYNTAX score (38) recently has
been developed to guide operators in this regard. This score
describes the coronary and clinical complexity of a patient
and might help us identify the most appropriate therapy
(PCI vs. CABG) on an individual level.
Study limitations. Our study is subject to the usual limita-
tions of meta-analyses, namely variation in study design and
publication bias. The meta-analysis is also dominated by the
Korean MAIN-COMPARE (Revascularization for Unpro-
tected Left Main Coronary Artery Stenosis: Comparison of
Percutaneous Coronary Angioplasty Versus Surgical Revas-
cularization) registry (13), which accounts for approximately
30% of the PCI patients in the synthesis. However, their
results are consistent with the other publications and are
similar based on heterogeneity. An additional caveat is that
with the exception of the New York Registry (17), data
came from highly experienced centers, with ?40 ULMCA
PCI cases performed. Therefore, similar results may not be
obtained by less experienced operators. A final limitation is
the absence of adequate published comparative data for the
third therapeutic option, medical therapy. Percutaneous
coronary intervention has not been compared with medical
therapy alone, but CABG has been shown to be superior to
medical therapy. Further, the follow-up in this analysis is up
to 3 years. The long-term durability of PCI versus CABG
remains undetermined and will require longer follow-up.
by on May 18, 2011 interventions.onlinejacc.org
Figure 4. Odds Ratio of TVR in PCI Versus CABG Patients
Odds ratio of target vessel revascularization (TVR) in PCI patients versus
CABG patients at 1, 2, and 3 years. Year 1: 1,240 PCI patients and 1,692
CABG patients; year 2: 417 PCI patients and 699 CABG patients; and year 3:
211 PCI patients and 447 CABG patients. Abbreviations as in Figure 1.
J A C C : C A R D I O V A S C U L A R I N T E R V E N T I O N S , V O L . 2 , N O . 8 , 2 0 0 9
Naik et al.
A U G U S T 2 0 0 9 : 7 3 9 – 4 7
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Also, it would be ideal to perform statistical pooling of
adjusted risk estimates of odds ratios or hazard ratios.
However, only 5 of the 10 studies reported adjusted risk
ratios that could be combined, and over one-third of the
patients would not be included. For this reason, we did not
include this analysis.
Conclusions
The notion that CABG is the only option for left main
stenosis for the prevention of death and MI, at least up to 3
years, can be re-evaluated. More importantly, we suggest
that a multidisciplinary management approach among sur-
geons, interventionalists, cardiologists, and primary care
physicians should occur with patients who have significant
left main disease. Then, based on patient and angiographic
factors, PCI can be considered a reasonable choice in
selected patients. Our results suggest that the current
American College of Cardiology/American Heart Associa-
tion guidelines regarding left main PCI (10) should be
revisited.
Reprint requests and correspondence: Dr. Raj Makkar, Cedars-
Sinai Heart Institute, Cardiovascular Intervention Center, Cedars-
Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles,
California 90048. E-mail: Raj.Makkar@cshs.org.
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Key Words: left main coronary artery ? stent ? coronary
artery bypass surgery ? coronary artery disease.
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doi:10.1016/j.jcin.2009.05.020
2009;2;739-747
J. Am. Coll. Cardiol. Intv.
Fontana, Saibal Kar, Prediman K. Shah, Robert E. Weiss, and Raj Makkar
Hursh Naik, Anthony J. White, Tarun Chakravarty, James Forrester, Gregory

Intervention or Surgery for Unprotected Left Main Coronary Artery Stenosis
A Meta-Analysis of 3,773 Patients Treated With Percutaneous Coronary
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