This randomized controlled trial compared percutaneous coronary intervention (PCI) using everolimus-eluting stents to coronary artery bypass grafting (CABG) for the treatment of left main coronary artery disease. The primary outcome was a composite of death, stroke, or myocardial infarction at 3 years. PCI was found to be non-inferior to CABG for the primary outcome. At 30 days, PCI had fewer adverse events like infections and bleeding, but more deaths, strokes and MIs. Between 30 days and 3 years, ischemia-driven revascularization was more common with PCI. Longer follow-up is still needed given differences in long-term medication use and revascularization between the treatments.

1. This article was published on October 31,
2016, at NEJM.org

2. BACKGROUND
Left main coronary artery disease is associated
with high morbidity and mortality owing to the
large amount of myocardium at risk.
European and U.S. guidelines recommend that
most patients with left main coronary artery
disease undergo coronary-artery bypass
grafting (CABG).
Randomized trials have suggested that
percutaneous coronary intervention (PCI) with
drug-eluting stents might be an acceptable
alternative for selected patients with left main
coronary disease.

3. DW Park, KB Seung, YH Kim, et al.: Long-term safety and efficacy of stenting versus coronary artery
bypass grafting for unprotected left main coronary artery disease: 5-year results from the MAIN-COMPARE
(Revascularization for Unprotected Left Main Coronary Artery Stenosis: Comparison of Percutaneous
Coronary Angioplasty Versus Surgical Revascularization) registry. J Am Coll Cardiol. 56:117-124 2010

4. Randomized studies of PCI vs Surgery for LMCA disease

9. Clinical
Outcomes
PRECOMBAT TRIAL-5 YRS SYNTAX TRIAL-5 YRS
Surgery
(N = 300)
Stents
(N = 300)
HR (95%
CI)
P value
Surgery
(N = 348)
Stents
(N = 357)
HR (95%
CI)
P value
MACCE 14% 18%
1.27 (0.84-
1.90)
.26 31% 37%
1.23 (0.95-
1.59)
.12
All
death/stro
ke/MI
10% 8%
0.89 (0.52-
1.52)
.66 21% 19%
0.91 (0.65-
1.27)
.57
All death 8% 6%
0.73 (0.39-
1.37)
.32 15% 13%
0.88 (0.58-
1.32)
.53
Cardiac
death
7% 4%
0.54 (0.26-
1.13)
.10 7% 9%
1.23 (0.71-
2.11)
.46
Stroke 1% 1%
0.99 (0.14-
7.02)
.99 4% 2%
0.33 (0.12-
0.92)
.03
MI 2% 2%
1.20 (0.37-
3.93)
.76 5% 8%
1.67 (0.91-
3.10)
.10
Revascul
arization
5.5% 11.4%
2.11
(1.16-
3.84)
.01 16% 27%
1.82
(1.28-
2.57)
<.001

10. Guidelines Class of Recommendation LOE
ACC/AHA 2011
IIa—For SIHD when both of the following are present: B
1.Anatomic conditions associated with a low risk of PCI procedural complications and a
high likelihood of good long-term outcome (e.g., a low SYNTAX score [≤22], ostial or
trunk left main stenosis)
1.Clinical characteristics that predict a significantly increased risk of adverse surgical
outcomes (e.g., STS-predicted risk of operative mortality ≥ 5%)
IIb—For SIHD when both of the following are present: B
1.Anatomic conditions associated with a low to intermediate risk of PCI procedural
complications and an intermediate to high likelihood of good long-term outcome (e.g.,
low-intermediate SYNTAX score <33, bifurcation left main stenosis)
1.Clinical characteristics that predict an increased risk of adverse surgical outcomes
(e.g., moderate-severe COPD, disability from prior stroke, or prior cardiac surgery; STS-
predicted risk of operative mortality >2%)
III—For SIHD in patients (vs. performing CABG) with unfavorable anatomy for PCI and
who are good candidates for CABG
B
ESC 2014
IIa—Left main (isolated or 1VD, ostium/shaft) B
IIb—Left main (isolated or 1VD, bifurcation)/left main + 2VD or 3VD, SYNTAX score ≤32 B
IIIb—Left main + 2VD or 3VD, SYNTAX score ≥33

12. Conclusions of the data available
● At one year and longer, CABG and PCI appear to have similar
rates of the combined end point of death from any cause, MI,
stroke.
● As the complexity of associated coronary artery disease
increases, assessed either by the SYNTAX score or as the
number of vessels that need revascularization, the benefit in
favour of CABG over PCI with stenting increases.
For patients with lower complexity coronary disease who can
undergo PCI at an acceptable risk and with reasonable
probability for success, PCI may be an acceptable or even
preferred option.
Still more data are available to validate this approach,
However, guidelines indicate that CABG should remain the
preferred option.

13. Conclusions of the data available
CABG is associated with a significantly higher
incidence of adverse in-hospital outcomes,
including death, MI, and stroke. However, the
long-term rates of death, MI, and stroke are
comparable or better depending on severity of
associated coronary artery disease.
PCI with stenting is associated with a higher
incidence of target vessel revascularization at
long-term follow-up.

14. WHY A NEW TRIAL??
The outcomes of PCI were acceptable only in the patients with
coronary artery disease of low or intermediate anatomical
complexity.
Because SYNTAX results represented a subgroup of a
subgroup, they were hypothesis generating.
PRECOMBAT and others were not adequately powered.
Routine angiographic follow up in PRECOMBAT
Moreover, contemporary metallic drug-eluting stents have a
better safety and efficacy profile than do the first-generation
stents used in earlier trials.
Surgical techniques and outcomes have also continued to
improve, and an evaluation of alternative methods of
revascularization for patients with left main coronary artery
disease is warranted in a contemporary trial.

15. This article was published on October 31,
2016, at NEJM.org

16. Trial design
EXCEL was an
International,
Open-label,
Multicenter (126 sites in 17 countries)
Randomized Trial
Compared Everolimus-eluting stents with CABG in
patients with LMCA disease.
Interventional cardiologists and cardiac surgeons
were represented equally

17. SPONSORSHIP
The trial was sponsored by Abbott
Vascular, which participated in the design
of the protocol and in the selection and
management of the sites
but was not involved in the writing of the
drafts of the manuscript or in the
management or analysis of the data

18. Inclusion criteria
1a. Unprotected LMCAD with angiographic diameter stenosis ≥70% (visually estimated),
or with angiographic diameter stenosis ≥50% but <70% with one or more of the
following present:
a. Non-invasive evidence of ischemia referable to a hemodynamically significant left
main lesion, and/or
b. IVUS MLA ≤6.0 mm2, and/or
c. FFR ≤0.80 OR
1b. LM equivalent disease: Left main distal bifurcation Medina 0,1,1 disease, in the
absence of significant angiographic stenosis in the left main coronary artery, may also
be randomized if either of the following conditions are present:
i. Both the ostial LAD and ostial LCX stenoses are ≥70% stenotic by visual
estimation, or
ii. If one or both of the ostial LAD and ostial LCX stenoses are ≥50% - <70%
stenotic by visual estimation, then this lesion(s) is demonstrated to be significant
either by
i. non-invasive evidence of ischemia in its myocardial distribution; and/or
ii. FFR ≤0.80; and/or
iii. IVUS MLA ≤4.0 mm2 (FFR is preferred).

19. Inclusion criteria
2. Clinical and anatomic eligibility for both PCI and CABG as
agreed to by the local Heart Team (interventionalist
determines PCI appropriateness and eligibility; cardiac
surgeon determines surgical appropriateness and
eligibility)
3. ≥18 years of age
4. Ability to sign informed consent and comply with all study
procedures , including follow-up for at least three years

21. Randomization was performed with the use of
an interactive voice-based or Web-based
system in block sizes of 16, 24, or 32, with
stratification according to diabetes (present vs.
absent), SYNTAX score (≤22 vs. ≥23), and
study center.

22. Treatment strategy-PCI
The goal of PCI was complete revascularization
of all ischemic territories with the use of
fluoropolymer- based cobalt–chromium
everolimuseluting stents (XIENCE, Abbott
Vascular).
Intravascular ultrasonographic guidance was
strongly recommended.
The use of heparin or bivalirudin was allowed
for procedural anticoagulation, and the use of
glycoprotein IIb/IIIa inhibitors was discouraged.
Dual antiplatelet therapy was initiated before
PCI and was continued for a minimum of 1 year
thereafter.

23. Treatment strategy-CABG
CABG was performed with or without
cardiopulmonary bypass (discretion of the operator).
The goal of CABG was complete anatomical
revascularization of all vessels 1.5 mm or larger in
diameter in which the angiographic diameter
stenosis was 50% or more; the use of arterial grafts
was strongly recommended.
Epiaortic ultrasonography and transesophageal
ultrasonography were recommended to assess the
ascending aorta and ventricular and valvular
function. Aspirin was administered during the
perioperative period, and the use of clopidogrel
during follow-up was allowed, but not mandatory,
according to the local standard of care.

24. Objectives and End Points
PRIMARY ENDPOINT OUTCOME
Composite rate of death from any
cause, stroke, or myocardial infarction at 3
years
Whether PCI was non-inferior to CABG
(The non-inferiority margin of 4.2 percentage points)

25. Objectives and End Points
SECONDARY OUTCOMES
1)Composite rate of death from any
cause, stroke, or myocardial infarction at 30 days
(Non-inferiority margin=2%)
2) Death, stroke , MI or Ischemia driven
revacularization at 3 years
(Non-inferiority margin=8.4%)

26. Objectives and End Points
ADDITIONAL SECONDARY OUTCOMES included
The individual components of the primary end point
Revascularization,
Stent thrombosis,
Symptomatic graft stenosis or occlusion,
Bleeding complications, and
A pre-specified composite of periprocedural major
adverse events.

27. RESULTS

30. Baseline
angiographic core
laboratory
assessment

31. Procedural data

32. Medicines used

33. Medicines used

34. Medicines used

36. End point PCI
N=948
CABG
N=957
DIFFERENC
E IN EVENT
RATE
P-VALUE
FOR
NON-
INFERIOR
ITY
HAZARD
RATIO (95%
CI)
P-
VALUE
FOR
SUPERI
ORITY
PRIMARY END
POINT
NO % NO % %points
(upper
confidenc
e limit)
DEATH,STROKE,
MI AT 3 YRS
137 15.4 135 14.7 0.7%
(4.0)
0.02
SECONDARY
END POINTS
DEATH,STROKE,
MI AT 30 DAYS
46 4.9 75 7.9 -3.1(-1.2) <0.001
DEATH,STROKE,
MI OR ISCHEMIA
DRIVEN REVASC
AT 3 YRS
208 23.1 174 19.1 4.0 (7.2) 0.01
DEATH,STROKE.
MI AT 3 YRS
137 15.4 135 14.7 - - 1.00
(0.79-
1.26)
0.98

37. Stone GW et al. N Engl J Med 2016. DOI: 10.1056/NEJMoa1610227
Time-to-Event Curves for the Primary Composite End Point and its
Components.

38. Stone GW et al. N Engl J Med 2016. DOI: 10.1056/NEJMoa1610227
Subgroup Analyses of the Primary Composite End Point.

39. Clinical endpoints at 30 days

41. Primary and hierarchical secondary endpoint events occurring within the
first 30 days and between 30 days and 3 years

42. SUMMARY
 Large Scale RCT – LMCA- PCI WITH XIENCE VS CABG
 PRIMARY OUTCOME : DEATH+STROKE+MI AT 3 YEARS-
PCI NON-INFERIOR
At 30 days PCI was better in terms of less infections/
procedure related complications esp periprocedural MI /
Bleeding
At 30 days, Death, Stroke and MI were lesser with PCI
But between 30 days and 3 years these were more
common with PCI
PLUS ischemia related revascularization was more
common with PCI at 3 years

43. Limitations
 Longer follow-up required
 Long term difference in medication
 Blinding of patients and investigators to the
treatments assigned was not possible
 24% patients had syntax >32 – furthur studies
are warranted in this subset

44. EXCEL VS SYNTAX
Syntax was hypothesis generating as it was a post
hoc analysis and not a pre-specified analysis.
First generation stents were used in syntax (higher
risk of ST)
IVUS was not used that frequently
CABG – also showed improvements in EXCEL with
greater use of off-pump surgery, arterial grafts anf
transesophageal echo , as compared to SYNTAX.
Periprocedural MI definition was standardized >10
times ULN

45. CONCLUSION
TAKE HOME MESSAGE
For the treatment of patients with left main
coronary artery disease and low or intermediate
SYNTAX scores, PCI with everolimus- eluting
stents was NONINFERIOR to CABG with respect
to the composite of death, stroke, or myocardial
infarction at 3 years

46. THANKS!

47. LANCET
31OCT 2016

53. THANKS!

54. STATISTICAL ANALYSIS
All principal analyses were performed with data
from the time of randomization in the intention
to-treat population, which included all patients
according to the group to which they were
randomly assigned, regardless of the treatment
received.
Sensitivity analyses were performed in the per-
protocol and as-treated populations.
Event rates were based on Kaplan–Meier
estimates in time-to-first-event analyses.

55. Noninferiority was calculated with the use of the Com–
Nougue approach to estimating the z statistic for the
Kaplan–Meier failure rates, with standard errors estimated
by means of Greenwood’s formula.
In time-to-first-event analyses, hazard ratios with 95%
confidence intervals were determined, and event rates
were compared with the use of the log-rank test.
Categorical variables were compared with the use of the chi-
square test or Fisher’s exact test.
Continuous variables were compared with the use of
Student’s t-test or the Wilcoxon rank-sum test for non-
normally distributed data.
For superiority, a two-sided P valueof 0.05 or less was
considered to indicate statistical significance.
All statistical analyses were performed with the use of SAS
software, version 9.4 (SAS Institute).