PCI vs CABG for Multivessel and

LMCA Disease:

NOBLE vs. EXCEL Trial

Alexander (Sandy) Dick, MD

Disclosures

• Interventionist

NOBLE and EXCEL

Clarity for PCI vs CABG Debate

WindeckerS, Piccolo R. JACC. 2016;68:1010-3

Capodanno D, et al, JACC, 2011; 58:1426-32

Cavalcante R, et al. JACC 2016;68:999-1009

Levine G, et al. JACC 2011;58:44-122

Windecker S, et al Eur Hrt J 2014;35:2541-619

Need for Updated LM Trial

• SYNTAX, LM subgroup

• 1 yr follow-up insufficient to capture true

benefit accrual of CABG

• 1st generation DES

• IVUS/FFR guidance uncommon

• Discretional angiographic f/u overinflated

number events in PCI arm

• Best standards CABG underused

Capodanno D, et al. Int J Cardiol 2012;156;1-3

Patients allocated to CABG in

analysis (n=592)

567 received CABG

23 received PCI

Randomized (n= 1201)

Allocated to PCI (n=598)

• Received PCI (n=585)

• Did not receive PCI (n=13)

• Died before PCI (n=1)

• Patient declined PCI (n=4)

• PCI operator declined (n=4)

• LMCA lesion not significant (n=4)

Allocated to CABG (n=603)

• Received CABG (n=570 )

• Did not receive CABG (n=33)

• Died before CABG (n=1)

• Patient declined CABG (n=15)

• Not eligible for CABG (n=15)

• Cross over by mistake (n=2)

Lost to follow-up (n=6)

• Emigration (n=1)

• Contact lost (n=2)

• Withdrawal (n=3)

Lost to follow-up (n=11)

• Emigration (n=0)

• Contact lost (n=0)

• Withdrawal (n=11)

Patients allocated to PCI in

analysis (n=592)

580 received PCI

7 received CABG

Enrollment2905 patients enrolledat 126 sites in 17 countries

Registry enrollment

N=1000

Randomized enrollment

N=747

Screening registry closed

Randomized enrollment

N=1158 additional

N=1905 total randomized

PCI with CoCr-EES

N=948

CABG

N=957

Followed through

initial treatment

(no outcomes data)

N=1000

Screening registry phase open

Stone GW, et al. NEJM 2016; Christiansen EH, et al. Lancet 2016

ResultsNon-procedural myocardial infarction

HR 2·88 (1·40–5·90); p=0·004

6·9%

1·9%

ResultsTotal repeat revascularization

HR 1·50 (1·04–2·17); p=0·03

10·4%

16·2%

ResultsStroke

HR 2·25 (0·92–5·48); p=0·07

4·9%

1·7%

Conclusions

• PCI did not meet non-inferiority for the primary endpoint of 5-year MACCE compared to CABG

• CABG was superior to PCI

• PCI resulted in higher rates of non-procedural myocardial infarctions

• Repeat revascularization was higher after PCI, primarily due to de novo lesions and non LMCA target lesion revascularization

• All-cause mortality was similar for PCI and CABG

Primary Endpoint

Death, Stroke or MI at 3 Years

No. at Risk:

PCI

CABG

5%

25%

20%

15%

10%

0%

1 6 12 24 36

850

817

784

763

445

458

HR [95%CI] =

1.00 [95% CI: 0.79, 1.26]

P = 0.98

875

836

0

948

957

896

868

15.4%14.7%

De

ath

, s

tro

ke

or

MI (%

)

CABG (n=957)

PCI (n=948)

Months

Primary Endpoint Definitions

• Death: Adjudicated due to CV, non-CV, or undetermined causes

• Peri-procedural MI (<72 hrs): CK-MB >10x URL, or >5x URL plus

either i) new pathological Q waves in ≥2 contiguous leads or new

LBBB, or ii) angio documented graft or coronary artery occlusion or

new severe stenosis with thrombosis, or iii) imaging evidence of new

loss of viable myocardium or new regional wall motion abnormality

• Spontaneous MI (≥72 hrs): CK-MB or troponin >1x URL plus new

ST-segment elevation or depression or other findings as above

• Stroke: Requires: 1) Rapid onset of a focal/global neurological deficit

with no other readily identifiable non-stroke cause; 2) Duration ≥24

hrs, or <24 hrs if i) pharmacologic or non-pharmacologic Rx; or ii)

positive brain imaging; or iii) death; 3) Confirmation by neurologist

plus confirmatory brain imaging or LP; 4) ≥1 increase in modified

Rankin Scale (mRS)

Stone GW, et al. NEJM 2016

Stone GW, et al. NEJM 2016

Christiansen EH, et al. Lancet 2016

Stone GW, et al. NEJM 2016; Christiansen EH, et al. Lancet 2016

Stone GW, et al. NEJM 2016; Christiansen EH, et al. Lancet 2016

Stone GW, et al. NEJM 2016; Christiansen EH, et al. Lancet 2016

Stone GW, et al. NEJM 2016; Christiansen EH, et al. Lancet 2016

Capodanno D, et al. JACC Card Interv 2016

SYNTAX Score

Site Reported Core LabLow (≤22)

Intermediate (23-32)

High (≥33)

PCI

CABG

59.2%40.8%

61.8%38.2%

Mean 20.6 ± 6.2

Mean 20.5 ± 6.1

P=0.52

42.8%

25.1%

32.2%

37.3%

23.4%

39.3%

Mean 26.9 ± 8.8

Mean 26.0 ± 9.8

P=0.005

Results

SYNTAX score subgroups

4.9%

1.9%

K-M estimates

HR 1·88 (1·23–2·89); p=0·0031 HR 1·16 (0·76–1·78); p=0·48 HR 1·41 (0·62–3·20); p=0·41

SYNTAX score assessed by independent corelab (CERC)

Stone GW, et al. NEJM 2016; Christiansen EH, et al. Lancet 2016

Core Lab DataPCI (N=942) CABG (N=936)

Qualifying LM lesion*

- LM coronary segment 97.6% 97.0%

- LM equivalent disease** 1.2% 1.5%

- Neither 1.3% 1.5%

Distal LM bifurcation or trifurcation ds. 81.8% 79.2%

# Diseased non-LM coronary arteries*

- 0 17.3% 17.8%

- 1 31.0% 31.2%

- 2 34.5% 31.5%

- 3 17.2% 19.4%

*DS ≥50% by QCA

**DS of both the ostial left LAD and ostial LCX ≥50% by QCA

PCI Procedure

Planned staged procedures 9.1%

Arterial access site*

- Femoral 72.9%

- Radial 26.9%

- Brachial 0.2%

IVUS guidance 77.2%

FFR assessment 9.0%

Hemodynamic support device* 5.2%

Contrast use* (cc) 256 ± 127

Fluoroscopy time* (min) 24 ± 16

*All procedures (index + planned staged); **Excludes pts with LM equivalent ds;†Max 4 vessels, including LM as a separate vessel

935 patients, 1021 planned procedures, 2287 stents

# Vessels treated per pt*† 1.7 ± 0.8

- LM 100.0%**

- LAD 28.3%

- LCX 16.6%

- RCA 26.7%

# Lesions treated per pt* 1.9 ± 1.1

# Stents implanted per pt* 2.4 ± 1.5

- Total stent length (mm)* 49.1 ± 35.6

Type of stents implanted*

- DES 99.8%

- EES 99.2%

- XIENCE 98.4%

Registry (n=1000)

Major reasons for exclusion

from randomization

Treatment

of registry patients

CABG PCI No revasc

64.8%33.1%

2.1%17.1%

36.0%

38.1%

29.9%

0% 10% 20% 30% 40% 50%

Heart team consensus ofineligibility for CABG

Heart team consensus ofineligibility for PCI

Site-assessed SYNTAX score ≥33

50-<70% LM stenosiswhich did not meet

criteria for hemodynamicsignificance

Of the 1747 pts enrolled during the registry period, 62% were eligible for PCI (1078; 331 reg +

747 rand), and 80% were eligible for CABG (1395; 648 reg + 747 rand)

OHI Unprotected LM PCI

• 68 unprotected LM in 10 months

• Only 8 EXCEL or NOBLE like patients

– Too high risk for CABG

– SYNTAX >32

– Refused CABG

• Uniform excellent angiographic results

Bottom Line EXCEL

• Contemporary PCI (best DES, IVUS) vs

suboptimal standards CABG (minor off-

pump and full arterial revascularization)

• Applicable selected patients amenable to

both procedures

• Noninferiority of PCI met for meaningful

range of endpoints; superiority not met

Bottom Line EXCEL

• Results largely explained by less

periprocedural MIs (large) in PCI group but

important catch in MIs up to 3yrs (may

continue with ongoing collection)

Bottom Line NOBLE

• Very long enrollment period

• Reported 5-yr KM estimates while having

a median 3 yr follow up. Portion patients

received first-generation DES at beginning

of trial

• Differences with EXCEL partly explained

by different MI definition, inclusion repeat

revascularization and focus on longer

follow up

Bottom Line NOBLE

• More thrombosis in NOBLE with SES/BES

than in EXCEL with EES: need stratified

analysis with stent type

• SYNTAX score results at odds with current

guidelines

Bottom bottom line

• New left main recommendations to be

patient-centered based on the early-and

long-term trade-offs of each procedure

Circulation, Feb 28, 2017

“….additional evidence that may influence

current guidelines by broadening the patient

pool that might undergo PCI.”

“….considering each patient’s individual

circumstances, including life expectancy,

comorbidities, extent of disease,

angiographic anatomy, likelihood and

perceived need for complete

revascularization, and patient preference.”

Revascularization Heart Team

• Most often none on committee has seen

patient

• No responsibility for decision

• If you don’t routinely

– Make evidence based decision (DM,

SYNTAX) in conjunction with referring

physician with special attention paid to

comorbid conditions and patient wishes

Heart Team Revasc vs TAVI

• Physician presenting has seen patient

• No complex imaging with Revasc

– CT, TEE, Mitral valve assessment,

Dobutamine Echo – contractile reserve

• Allied team members such as geriatric

assessment much more relevant TAVI

Sample size

• SYNTAX trial MACCE after 2 years*(30% of PCI,23% of CABG)

• A HR of 1·35 was defined accordingly as the clinically acceptable non-inferiority limit not to be exceeded by the one-sided 95% CI

• 1- β (power) = 80%

• 275 events, with 1200 patients, 600 in each group needed

• The primary endpoint assessment was January 2015 changed to include MACCE endpoints occurring between 2 and 5 years to reach a total of 275 events

• September 2015 it was estimated that 275 events could not be reached within full 5 years (January 2020), and the primary endpoint assessment was changed to median 3 years

*Predicted from preliminary 1-year results in the SYNTAX trial