BACKGROUND

Significant LMCA disease affects:

85% of LV myocardium in R-dominant
100% of LV myocardium in L-dominant
Medical management alone 50% mortality
@ 3 yrs
CABG is gold standard - long track record of
safety and efficacy with 30 day mortality <
2 % in US database
Recent randomized trials show PCI as an
alternate non-inferior option.
 PCI vs CABG in ULMCA
EXCEL
NOBLE
PROCOMBAT
SYNTAX
 SYNTAX TRIAL:
PCI with DES(Paclitaxel) vs CABG
Complex CAD- ULMCA and TVD
5 yrs follow-up
Three terciles (<22, 22-32, >32)
PCI(357) vs CABG(348) in ULMCA:
No significant difference in the incidence of
MACCE events
No significant difference in the incidence of
stent thrombosis vs graft occlusion
 In the lower 2 syntax score terciles
(0-32):
No significant difference in MACCE
events
PCI appeared to have better survival
In high syntax score tercile (>32):
Both MACCE and mortality were higher
in PCI group
 PRECOMBAT STUDY:
PCI with DES(Sirolimus)(300) vs
CABG(300) in ULMCA
Mean syntax score-24
No significant difference in MACCE,
death, MI, stroke @ 1 yr
Significantly increased incidence of
ischemia driven revascularization in PCI
group
 EXCEL trial
(XIENCE vs CABG)
International, open-label, multicenter randomized
trial
Sponsored by Abbott Vascular
From September 29, 2010, to March 6, 2014
Study Design
1:1 randomization to either PCI with XIENCE everolimus-
eluting stents (n = 948) or CABG (n = 957).
Total number screened: 2,905
Total number of enrollees: 1,905
Duration of follow-up: 3 years
Mean patient age: 66 years
Percentage female: 23%
 Inclusion criteria:
Unprotected left main coronary artery disease
With 70% stenosis,or
50% to <70% with either:
1) noninvasive evidence of left main ischemia,
2) intravascular ultrasound minimum lumen area 6.0
mm2, or
3) fractional flow reserve 0.80
SYNTAX score 32
Clinical and anatomic eligibility for both PCI
and CABG, as agreed to by the local Heart
Team
 Exclusion criteria:
Prior CABG or left main PCI any time
Prior non-left main PCI within 1 year
Need for cardiac surgery other than
CABG
Inability to tolerate dual antiplatelet
therapy for 1 year
Creatine kinase-myocardial band >
upper limit of normal
 Primary composite end point:
Death from any cause, stroke, or myocardial
infarction at 3 years.
Secondary outcomes:
Death, stroke, or MI at 30 days for PCI vs. CABG
Death, stroke, or MI between 30 days and 3
years for PCI vs. CABG
Stent thrombosis or graft occlusion at 30 days
Stent thrombosis or graft occlusion at 3 years
Ischemia-driven revascularization at 3 years
 Timing of follow-
Endpoint Powered for
up
Primary endpoint: Median 3 years,
Non-inferiority
Death, stroke or MI minimum 2 years
Secondary endpoint
#1: 30 days Non-inferiority
Death, stroke or MI
Secondary endpoint
#2a: Median 3 years,
Non-inferiority
Death, stroke, MI or minimum 2 years
IDR
Secondary endpoint
Median 3 years,
#2b: Superiority
minimum 2 years
Death, stroke or MI
 Clinical follow-up was performed at 1
month, 6 months, and 1 year and
then annually through 5 years.
The primary composite end point was
assessed at a median follow-up of 3
years, with a minimum follow-up of 2
years for all patients.
 PCI (N=948) CABG (N=957)
Age(years) 66.09.6 65.99.5
Male 76.2% 77.5%
Countryofenrollment
-Europe 56.3% 56.5%
-NorthAmerica 40.2% 38.8%
-Other 3.5% 4.7%
Diabetes 30.2% 28.0%
-Insulin-treated 7.7% 7.7%
Hypertension,medicallytreated 74.5% 73.9%
Hyperlipidemia,medicallytreated 71.5% 69.3%
Currentsmoker 24.1% 20.8%
PriorPCI 18.4% 15.9%
Congestiveheartfailure 7.1% 6.2%
PriorstrokeorTIA 5.5% 7.0%
 PCI (N=948) CABG (N=957)
Peripheralvasculardisease 10.3% 8.8%
COPD 6.9% 8.5%
Clinicalpresentation
-RecentMI(within7days) 15.0% 14.8%
-Unstableangina,biomarkernegative 24.2% 24.6%
-Stableangina 53.1% 53.2%
-Silentischemiaorother 7.7% 7.4%
Bodymassindex(kg/m2) 28.65.0 28.8 4.9
Renalinsufficiency(CrCl<60mL/min) 17.6% 15.4%
Anemia(WHOcriteria) 26.9% 22.6%
Thrombocytopenia(<150,000cells/mm3) 7.0% 7.0%
Leftventricularejectionfraction(%) 57.09.6 57.39.0
 Syntax Score
Low(22)
SiteReported Intermediate(23-32)
CoreLab
High(33)

42.8%
40.8%
59.2% PCI 32.2%

25.1%

P=0.52 P=0.005
Mean 20.6 6.2 Mean 26.9 8.8

38.2% 37.3%
61.8% CABG 39.3%

23.4%

Mean 20.5 6.1 Mean 26.0 9.8

 PCI (N=942) CABG (N=936)
QualifyingLMlesion*
-LMcoronarysegment 97.6% 97.0%
-LMequivalentdisease** 1.2% 1.5%
-Neither 1.3% 1.5%
DistalLMbifurcationortrifurcationds. 81.8% 79.2%
#Diseasednon-LMcoronaryarteries*
-0 17.3% 17.8%
-1 31.0% 31.2%
-2 34.5% 31.5%
-3 17.2% 19.4%
 Other salient features/characteristics:
Diabetics: 29%
Prior PCI: 17%
Stable angina-53%; recent myocardial
infarction (MI)-15%; unstable angina-24%
Mean left ventricular ejection fraction: 57%
SYNTAX scores: low (22) for PCI vs. CABG,
32.2% vs. 39.3%; high (33), 25.1% vs. 23.4%
Distal left main trunk bifurcation lesion: 81%
Additional single-vessel disease-31%; two-
vessel disease-33%; three-vessel disease-18%
 PCI arm: IVUS-77.2%; hemodynamic
support-5.2%; stents per patient-2.4;
stented length-49.1 mm
CABG arm: off-pump-29.4%; conduits
per patient-2.6; internal mammary
artery use-99%
Medication use: aspirin-99%; statin-
95%; P2Y12 inhibitor for PCI vs. CABG-
97.6% vs. 32.6%; p < 0.001
 PCI group
Complete revascularization of all
ischemic territories with EES
Provisional LM bifurcation treatment
preferred
IVUS guidance strongly
recommended
DAPT pre-loading and treatment for
1 year
Routine angiographic follow-up not
permitted
 CABG group
Performed w/ or w/o CPB per
operator discretion
Complete anatomic revascularization
of all vessels 1.5 mm in diameter
with 50% DS
Arterial grafts strongly recommended
Epi-aortic ultrasound and TEE
recommended
Clopidogrel use during FU allowed
but not mandatory
 PCI procedure
935patients,1021plannedprocedures,2287stents
Plannedstagedprocedures 9.1% #Vesselstreatedperpt* 1.70.8
-LM 100.0%**
Arterialaccesssite*
-LAD 28.3%
-Femoral 72.9%
-LCX 16.6%
-Radial 26.9%
-RCA 26.7%
-Brachial 0.2% #Lesionstreatedperpt* 1.91.1
IVUSguidance 77.2% #Stentsimplantedperpt* 2.41.5
-Totalstentlength(mm)* 49.135.6
FFRassessment 9.0%
Typeofstentsimplanted*
Hemodynamicsupportdevice* 5.2%
-DES 99.8%
Contrastuse*(cc) 256127
-EES 99.2%
Fluoroscopytime*(min) 2416 -XIENCE 98.4%

*All procedures (index + planned staged); **Excludes pts with LM equivalent ds;

Max 4 vessels, including LM as a separate vessel
 CABG Procedure
923patientsandprocedures
#Conduitsperpt 2.60.8
Off-pumpCABG 29.4%
-Arterialconduits 1.40.6

-Venousconduits 1.20.9
On-pumpbypassduration(min) 8345
AnyIMAused 98.8%

-Crossclampduration(min) 5527 BilateralIMAused 28.8%

Anyradialarteryused 6.0%
Epi-aorticultrasound 13.1% Onlyarterialconduitsused 24.8%

Vesselsbypassedperpt
Transesophagealultrasound 42.3% -LAD 98.8%

-LCX 88.2%
Hemodynamicsupportdevice 3.5%
-RCA 37.8%
 Primary and Hierarchical
Secondary Clinical Outcomes
PCI CABG Diff [upper PNI PSup
HR [95%CI]
(n=948) (n=957) confidence limit]

Primary endpoint

Death,strokeorMI
at3years
15.4% 14.7% 0.7%[4.0%] 0.018 - -

Secondary endpoints

Death,strokeorMI
at30days
4.9% 7.9% -3.1%[-1.2%] <0.001 - -

Death,stroke,MIor
ischemia-drivenrevasc 23.1% 19.1% 4.0%[7.2%] 0.01 - -
at3years

Death,strokeorMI
at3years
15.4% 14.7% - - 1.00[0.79,1.26] 0.98

The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years,
2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven
revascularization at 3 years.
 Primary and Hierarchical
Secondary Clinical Outcomes
PCI CABG Diff [upper PNI PSup
HR [95%CI]
(n=948) (n=957) confidence limit]

Primary endpoint

Death,strokeorMI
at3years
15.4% 14.7% 0.7% [4.0%] 0.018 - -

Secondary endpoints

Death,strokeorMI
at30days
4.9% 7.9% -3.1%[-1.2%] <0.001 - -

Death,stroke,MIor
ischemia-drivenrevasc 23.1% 19.1% 4.0%[7.2%] 0.01 - -
at3years

Death,strokeorMI
at3years
15.4% 14.7% - - 1.00[0.79,1.26] 0.98

The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years,
2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven
revascularization at 3 years.
 Primary and Hierarchical
Secondary Clinical Outcomes
PCI CABG Diff [upper PNI PSup
HR [95%CI]
(n=948) (n=957) confidence limit]

Primary endpoint

Death,strokeorMI
at3years
15.4% 14.7% 0.7%[4.0%] 0.018 - -

Secondary endpoints

Death,strokeorMI
at30days
4.9% 7.9% -3.1%[-1.2%] <0.001 - -

Death,stroke,MIor
ischemia-drivenrevasc 23.1% 19.1% 4.0%[7.2%] 0.01 - -
at3years

Death,strokeorMI
at3years
15.4% 14.7% - - 1.00[0.79,1.26] 0.98

The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years,
2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven
revascularization at 3 years.
 Primary and Hierarchical
Secondary Clinical Outcomes
PCI CABG Diff [upper PNI PSup
HR [95%CI]
(n=948) (n=957) confidence limit]

Primary endpoint

Death,strokeorMI
at3years
15.4% 14.7% 0.7%[4.0%] 0.018 - -

Secondary endpoints

Death,strokeorMI
at30days
4.9% 7.9% -3.1%[-1.2%] <0.001 - -

Death,stroke,MIor
ischemia-drivenrevasc 23.1% 19.1% 4.0%[7.2%] 0.01 - -
at3years

Death,strokeorMI
at3years
15.4% 14.7% - - 1.00[0.79,1.26] 0.98

The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years,
2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven
revascularization at 3 years.
 Primary and Hierarchical
Secondary Clinical Outcomes
PCI CABG Diff [upper PNI PSup
HR [95%CI]
(n=948) (n=957) confidence limit]

Primary endpoint

Death,strokeorMI
at3years
15.4% 14.7% 0.7%[4.0%] 0.018 - -

Secondary endpoints

Death,strokeorMI
at30days
4.9% 7.9% -3.1%[-1.2%] <0.001 - -

Death,stroke,MIor
ischemia-drivenrevasc 23.1% 19.1% 4.0%[7.2%] 0.01 - -
at3years

Death,strokeorMI
at3years
15.4% 14.7% - - 1.00[0.79,1.26] 0.98

The pre-specified non-inferiority margins (deltas) were 4.2% for death, stroke or MI at 3 years,
2.0% for death, stroke or MI at 30 days, and 8.4% for death, stroke, MI or ischemia-driven
revascularization at 3 years.
 Primary Endpoint
Death, Stroke or MI at 3 Years
25%

CABG(n=957)
Death, stroke or MI (%)

PCI(n=948)
20%

15.4%
15%
14.7%

10%

HR[95%CI]=
5%
1.00[95%CI:0.79,1.26]
P=0.98
0%

01 6 12 24 36
No.atRisk:
Months
PCI 948 896 875 850 784 445
CABG 957 868 836 817 763 458
 3-Year Death, Stroke or MI
PCI CABG Favors Favors
Subgroup (N=948) (N=957) HR [95% CI] PCI CABG P (Int)
All patients 15.4% 14.7% 1.00[0.79,1.26]
Age (median cutoff)
-67years 18.7% 15.0% 1.22[0.89,1.69]
0.07
-<67years 12.2% 14.4% 0.78[0.55,1.11]
Gender
-Male 14.0% 14.9% 0.87[0.66,1.14]
0.06
-Female 19.7% 14.1% 1.48[0.93,2.41]
Diabetes mellitus
-Yes 21.2% 19.4% 1.04[0.70,1.55]
0.77
-No 13.3% 13.1% 0.97[0.72,1.30]
Chronic kidney disease
-eGFR60ml/min 24.5% 19.3% 1.24[0.75,2.07]
0.36
-eGFR>60ml/min 13.5% 13.6% 0.95[0.72,1.25]
Geographic location
-NorthAmerica 15.5% 12.4% 1.22[0.82,1.82]
-Europe 15.5% 15.6% 0.95[0.69,1.29] 0.14
-Other 9.5% 22.2% 0.37[0.08,1.20]
0.1 0.5 0.8 1 1.5 2 5
Hazard Ratio [95% CI]
 3-Year Death, Stroke or MI
PCI CABG Favors Favors
Subgroup (N=948) (N=957) HR [95% CI] PCI CABG P (Int)
All patients 15.4% 14.7% 1.00[0.79,1.26]
Left ventricular ejection fraction
-50% 14.7% 14.4% 0.98[0.75,1.27]
0.99
-<50% 20.4% 18.2% 0.98[0.52,1.83]
Non-LM diseased coronary arteries
-0 14.6% 14.4% 0.99[0.54,1.79]
-1 12.3% 16.0% 0.72[0.46,1.12]
0.78
-2 18.8% 12.7% 1.44[0.96,2.21]
-3 15.2% 16.8% 0.87[0.50,1.48]
LMbifurcationortrifurcationstenosis50%
-Yes 15.6% 15.3% 0.98[0.75,1.27]
0.82
-No 14.8% 12.9% 1.05[0.59,1.87]
Syntax score (site reported)
-22 14.3% 14.4% 0.95[0.70,1.31] 0.70
-23-32 17.0% 15.4% 1.05[0.73,1.51]
Syntax score (core lab assessment)
-22 10.3% 13.3% 0.71[0.44,1.13]
-23-32 17.6% 16.5% 1.02[0.71,1.47] 0.49
-33 16.9% 14.3% 1.15[0.71,1.87]
0.1 0.5 0.8 1 1.5 2 5
Hazard Ratio [95% CI]
 CONCLUSIONS
Treatment of patients with ULMCAD and low or
intermediate SYNTAX scores with CoCr-EES:
Similar rates of the primary endpoint of death, stroke or MI
at 3 years compared to CABG
Fewer adverse events within 30 days compared to CABG

PCI may thus be considered an acceptable or even

preferred revascularization modality for selected
patients with LMCAD, a decision which should be
made after heart team discussion, taking into
account each patients individual circumstances and
preferences
 NOBLE trial:
PCI with biodegradable polymer DES
(BIOLIMUS) vs CABG in ULMCA
1:1 randomization
1200 patients
5 yrs follow-up
 NOBLE trial results
Primary outcome (Death, MI, Stroke,
Repeat revascularization):
PCI 29% vs CABG 19% (p=0.006)
Repeat revascularization:
PCI 16% vs CABG 10% (p=0.03)
Secondary outcomes:
Stent thrombosis 0.3% vs Graft occlusion
0.4% (p=0.22)
30 day stroke:
PCI 0% vs CABG 0.7% (p=0.04)
 NOBLE - Conclusions
PCI with Biolimus is inferior to CABG
Repeat revascularization is higher in
PCI group
30-day stroke events are higher in
CABG group
Take home message..