Multi-vessel Disease Patient with Coronary Artery Disease...

V. Voudris MD PhD FESC FACCDirector 2nd InterventionalCardiology DivisionChairman Cardiology DepartmentOnassis Cardiac Surgery Center

Multi-vessel Disease Patient with Coronary ArteryDisease: Is There any Difference in Treatment After

SYNTAX Study

Conflict of Interest

Advisory Board : Medtronic

© Cordis Corporation 2007© Cordis Corporation 2007 3

770,000810,000

850,000920,000

980,0001,030,000

1,092,0001,037,000

305,000 289,000296,000299,500395,000

485,000

542,000

514,000

200,000

500,000

800,000

1,100,000

PCI Vs CABG: New Vs Old Technology

Sources: Cordis Database, Morgan Stanley

2000 2001 2002 2004 2005 2006 20072003

Angioplasty

Bypass Surgery

The Patient with LM / 3 VD CAD

Interventionalist

Surgeon

Patient

Interventionalist

SYNTAX Trial• 1800 patients with 3 vessel CAD randomized to PCI

with Taxus drug-eluting stents or CABG– ~ 28% diabetic– ~ 33% with LM disease– 4.6 stents per patient– Average of 86 mm of stent (1/3 with >100 mm)– Primary Endpoint : MACCE at 1-year

• Yearly F/U thereafter (up to 5 years)Serruys, et al. N Engl J Med 2009;360:961-72

SYNTAX Trial - 5 Year

Mohr, et al. Lancet 2013;381:629-38

All Cause Mortality

Stroke

SYNTAX -


5 Year Rates of Death, Stroke, or MI

SYNTAX - 5 Year MACCE


SJ Head et al. European Heart Journal (2014) 35, 2821–2830

CABG vs. PCI for patients with 3 vessel disease:5 - year FU of the SYNTAX trial


SYNTAXTrial :5 YearsResults

3 VesselDiseasePatients

Syntax Trial – 3 Vessel Disease PatientsThe 5-year analysis of patients with 3VD randomized in theSYNTAX trial demonstrated that treatment with PCI resulted insignificantly higher rates of MACCE, which were driven notonly by increased rates of repeat revascularization but also bysignificantly higher all-cause death and MI

Stroke rates were comparable between CABG and PCI

Treatment with PCI was found to be an independent predictor,not only of 5-year MACCE but also of all-cause death andcomposite safety endpoint of death/stroke/MI


CABG vs. PCI for patients with 3 vessel disease:5 - year FU of the SYNTAX trial

Syntax Trial – IncompleteRevascularizationIncomplete revascularization occurs more frequently in

patients with chronic total occlusions undergoing PCIresulting in large areas of non-revascularized/ischaemic

myocardium that could potentially increase the risk ofdeath during follow-up

Incomplete revascularization in CABG usually encompassessmall vessels with less ischaemic myocardium at riskdiffusely diseased vessels which are often well

collateralized

Five-year incidence of cardiac events in left maincoronary artery (LM) patients

MC Morice et al. Circulation. 2014;129:2388-2394

SYNTAX LM: Medically-treated Diabetic Patients5-year Outcomes (N=452)

12,95,4 4,7

14,619,5

9,03,0

35,3

0

10

20

30

40

50

60

TAXUS (n=231)CABG (n=221)

All Death MI CVA Revasc.

P=0.06

Patie

nts

(%)

P=0.20 P=0.34 P<0.001P<0.001

29.0

46.5

MACCEITT populationCumulative KM Event Rate; log-rank P value

Site-reported data

Heterogeneity in the Left Main Group

0102030405060

P=0.12 P=0.30 P=0.67 P=0.24 P=0.04

MACCE to 5 Years Left Main SubsetsPa

tient

s (%

)

TAXUSCABG

Dominance

SYNTAXscore

Diseased

Segment

#

Tota

lOc

clusio

n

Trifurcation

Bifurcation

Aorta OstialSevere

Tortuosity

Leng

thHeavy

Calcific

atio

nThrombus

DiffuseSmall

WWW.SYNTAXSCORE.COM

SYNTAX Score - 5 Year MACCELowest SYNTAX Tertile (0-22)

All Patients


All Patients

Middle SYNTAX Tertile (23-32)

All Patients

Highest SYNTAX Tertile (33+)

Five-year Incidence of Cardiac Events in Left Main(LM) Coronary Artery Patients

MC Morice et al. Circulation. 2014;129:2388-2394

HIGHER SYNTAX SCOREFAVOURS CABG

LOWER SYNTAX SCOREFAVOURS PCI

PCI

CABG

SYNTAX: Definite/Probable ARC Stent Thrombosis to 5 Years (Per Patient)

0

6

12

(3/896) (23/893) (15/874) (11/850) (12/830)

Days Post-procedure

Acute≤1 d

Subacute2-30 d

Late31-365 d

Very Late(10/803) (7/768)

366-730 d

731-1095 d

1096-1460 d

1461-1825 d

0.3

2.61.7 1.3 1.4 1.2 0.9

~3% ST rate within 30 days, and then~1-2%/yr thereafter

Serruys PW. TCT2012

SYNTAX: Short- and Long-term Clinical Impact of StentThrombosis and Graft Occlusion at 5 Years

Conclusion: Rates of stent thrombosis, graft occlusion at 5 years aresimilar, but stent thrombosis has greater effect on mortality

Analysis of patients with left main or 3-vessel disease undergoing PCI with Taxus(n = 871) or CABG (n = 805), using per protocol and ARC or ARC-like definitions

5-Year Follow-upARC Definite Stent

Thrombosis(n = 47)

ARC-like DefiniteGraft Occlusion

(n = 32)P Value

0-30 Days 3.0% 1.0% 0.03

31 Days-5 Years 4.2% 4.5% 0.68

Cardiac mortality was 35.4% in patients with stent thrombosis comparedwith 0% in patients with graft occlusion

Farooq V, et al. J Am Coll Cardiol.2013

• Higher initial cost of PCI vs CABG (due to the cost of stents, repeatrevascularization, medications) narrowed over 5 years

• Projected beyond 5 years, CABG provides gains in both life expectancyand quality-adjusted life-years, meeting the threshold for society’swillingness to pay

• In subgroup analyses, PCI was cost-effective for patients with a lowSYNTAX score (≤ 22) or left main disease

Five-year data from SYNTAX (n = 1,800) used to extrapolate costs, lifeexpectancy, and quality-adjusted life expectancy over a lifetime

Cost-Effectiveness of PCI with DES vs Bypass Surgeryfor Patients with 3-Vessel or Left Main CAD

Implications: For most patients with 3-vessel or left main disease, CABGis preferred for both clinical and economic reasons, but PCI is cost-effective for less complex anatomy

Cohen DJ, et al. Circulation. 2014;Epub ahead of print.

Syntax Trial MessagesThe treatment effect of PCI vs. CABG differed significantlybetween patients with LM and 3 vessel disease

left main PCI has become more common since theresults from the SYNTAX trial established similarsafety and efficacy in comparison with CABG

for multivessel disease this study for the first timeprovides robust evidence that CABG is superior to PCIusing first-generation DES in reducing long-term hardclinical endpoints of death and MI

Syntax Trial MessagesCABG should remain the standard of care for patientswith complex lesions (high or intermediate SYNTAX scores)

For patients with less complex disease (low SYNTAX scores)or left main coronary disease (low or intermediate SYNTAXscores), PCI is an acceptable alternative

All patients with complex multivessel coronary arterydisease should be reviewed and discussed by botha cardiac surgeon and interventional cardiologist to reachconsensus on optimum treatment

Implementation of the SYNTAX results in recent ESCguidelines on myocardial revascularization

.

European Heart Journal (2014) 35, 2541-2619

Limitations of the Syntax Trial

The non-inferiority end point of 12-monthMACCEs was not met in the overall population

Thus, the analysis of LM or 3 vessel diseasepatients should be considered observationaland hypothesis generating

• The conventional SYNTAX Score is advocated inthe US & European revascularisation guidelinesas a tool to aid the Heart Team

• These guidelines also state that clinical variablesshould be taken into account

• Recent attempts have been made to merge theSYNTAX Score with cardiac based surgical riskscores to overcome this limitation

Limitations of the SYNTAX Score

SYNTAX Score IIDesigned to Objectively to Balance Patient Risk To Guide

Decision Making Between CABG and PCI

25

Tables

Table 1

Title: Development (SYNTAX Trial) (a) and validation (DELTA Registry) (b) data

for the SYNTAX Score II.

Legend: Hazard ratios (HR) in a multivariable Cox Proportional Hazards Model for

the SYNTAX Score II are shown for the CABG and PCI arms, followed by the

interaction effects (HRPCI/HRCABG) in influencing long term mortality between CABG

and PCI.

CABG 4-Year DeathMultivariable adjustedHR and 95% CI

PCI 4-Year DeathMultivariable adjustedHR and 95% CI

Interaction EffectHRPCI/HRCABG

(95% CI and p-value)a) Development PopulationSYNTAX Trial (n=1800)SYNTAX Score (per 10 point increase)Age (per 10 year increase)Creatinine Clearance† (per 10 ml/min increase)LV Ejection Fraction (per 10% increase)Peripheral Vascular Disease†ULMCA DiseaseFemaleCOPD

0.97 (0.79, 1.18)1.88 (1.34, 2.64)0.91 (0.77, 1.07)0.84 (0.61, 1.16)2.79 (1.66, 4.71)1.47 (0.93, 2.34)0.59 (0.32, 1.10)2.84 (1.64, 4.90)

1.27 (1.08, 1.50)1.29 (0.97, 1.71)0.82 (0.72, 0.93)0.56 (0.43, 0.73)2.79 (1.72, 4.53)0.82 (0.54, 1.23)1.70 (1.11, 2.60)1.35 (0.74, 2.47)

1.32 (1.01, 1.71; p=0.039)0.69 (0.44, 1.07; p=0.095)0.89 (0.73, 1.10; p=0.30)0.67 (0.44, 1.00; p=0.053)1.00 (0.49, 2.04; p=1.00)0.56 (0.30, 1.03; p=0.062)2.87 (1.35, 6.07; p=0.0059)0.48 (0.21, 1.08; p=0.074)

b) External Validation PopulationDELTA Registry (n=2891)SYNTAX Score (per 10 point increase)Age (per 10 year increase)Creatinine Clearance (per 10 ml/min increase)LV Ejection Fraction (per 10% increase)Peripheral Vascular Disease*ULMCA DiseaseFemaleCOPD*

1.12 (0.95, 1.32)1.46 (1.15, 1.85)0.91 (0.78, 1.06)0.59 (0.47, 0.75)1.37 (0.68, 2.79)

-0.52 (0.31, 0.87)

3.63 (1.31, 10.04)

1.32 (1.20, 1.46)1.34 (1.19, 1.52)0.93 (0.86, 1.00)0.57 (0.50, 0.65)1.77 (1.01, 3.09)

-1.09 (0.82, 1.46)1.97 (0.88, 4.42)

1.18 (0.98, 1.42; p=0.083)0.92 (0.70, 1.21; p=0.56)1.02 (0.86, 1.21; p=0.82)0.96 (0.72, 1.27; p=0.75)1.29 (0.51, 3.22; p=0.59)

-2.09 (1.16, 3.76; p=0.014)0.54 (0.20, 1.47; p=0.23)

† Retained in SYNTAX Score II to improve the predictive accuracy of 4-year mortality in the CABG

and PCI arms (weak [CrCl] or negligible [PVD] interaction effects between CABG and PCI for 4-year

mortality)

* Data reported by the study sites in 1363/2891 (47.1%) patients for PVD and 1061/2891 (36.7%)

patients for COPD.

Abbreviations: CABG coronary artery bypass graft, PCI percutaneous coronary intervention, HR

hazard ratio, SD standard deviation, ULMCA unprotected left main coronary artery, LV left

ventricular, COPD chronic obstructive pulmonary disease

Age

HIGHER AGEFAVOURS PCI

YOUNGER AGE FAVOURSCABG

PCI

CABG

SYNTAX Score II Left VentricularEjection Fraction

LOWER LVEFFAVOURS CABG

HIGHER LVEFFAVOURS PCI

CABG

PCI

COPDFAVOURS PCI

PCI

CABG

SYNTAX Score IICOPD

ULMCA DISEASEFAVOURS PCI

PCI

CABG

Unprotected LMCAD

Female Gender

FEMALE GENDERFAVOURS CABG

PCI

CABG

Findings recently shown (In Press) on multivariable analyses of theSYNTAX Trial, demonstrating female gender to be an independentcorrelate of long term mortality after PCI

Syntax Trial Limitations – FuturePerspectives

Newer-generation DES have been developed since theuse of the paclitaxel-eluting stent in the SYNTAX trial andhave replaced the latter in current clinical practice dueto significant reductions in MI, ST, and repeat revascularization

We are waiting the EXCEL trial, which evaluates theperformance of the everolimus eluting stent vs.revascularization surgery in patients with lesions of leftmain coronary artery

“In your case, Dave, there’s a choice: elective surgery,outpatient medical therapy, or whatever’sin the box that our lovely Carol is holding.”

Thank You

CABG

PCI

LM and 1 or 2 VD and 3 VDwith Low Syntax Score

patients

CABG

PCI

LM and 3 VD with highSyntax Score patients

Multi-vessel Disease Patient with Coronary Artery Disease...

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