Alfredo E Rodriguez MD,PhD,FACC,FSCAI Founder

Cardiovascular Research Center(CECI) Director

Cardiology Fellow Training Program

Otamendi Hospital Director

Cardiac Unit Otamendi Hospital/Las Lomas

Editor in Chief Revista Argentina de Cardioangiologia

Intervencionista(RACI)

Associate Director TCT 2015/2017

Simposio TCT/CACI/SAC

Buenos Aires 13 y 14 de Octubre 2016

Evolución a Largo Plazo de los Pacientes

Revascularizados con CABG yPCI:

Mi Visión Despues de 25 Anos de Estudios

Randomizados y Observacionales

Long-Term Safety and Efficacy of Percutaneous Coronary Intervention

With Stenting and Coronary Artery Bypass Surgery for Multivessel

Coronary Artery Disease

A Meta-Analysis With 5-Year Patient-Level Data From the ARTS, ERACI-II,

MASS-II, and SoS Trials

Joost Daemen, Eric Boersma, Marcus Flather, Jean Booth, Rod Stables, Alfredo

E Rodriguez, Gaston Rodriguez-Granillo, Whady A. Hueb, Pedro A. Lemos,

Patrick W. Serruys,

Daemen et al. Circulation. 2008;118:1146-1154

Freedom From Death (A) and from

Death and Myocardial Infarction (B)

Chang M et al JACC,2016,68

Pooled Data Syntax(TAXUS) and BEST( EES) vs CABG

Chang M et al JACC,2016,68

Chang M et al JACC,2016,68

SJ Park et al. N Engl J Med. 2015 Mar 26;372(13):1204-12.

Long-Term Clinical

End Points after Randomization,

According to Study Group

SJ Park et al. N Engl J Med. 2015 Mar 26;372(13):1204-12.

Park et al. N Engl J Med. 2015 Mar 26;372(13):1204-12.

What we done in PCI

between both analysis?

30 Years Journey of PCI in Multiple Vessels CAD: Insights

from ERACI I to IV Studies

14.5 %

15.4 %

No differences in stent

thrombosis/graft

occlusion rate but…….

DEATH

ST GO

35.4% 0.0%

SYNTAX 5 Years, JACC, 2013

In spite of different DES designs (Taxus & EES)

they are sharing similar PCI strategy

SJ Park et al. NEJM. 2015 Mar 26;372(13).

Sianos G, et al. EuroIntervention. 2005 Aug;1(2):219-27.

The SYNTAX lesion score is

calculated by grading 11 types of

lesions by answering sequential

interactive questions

YES: Non Guided

-Intermediate (50 to 69%) or

Severe Stenosis (≥ 70%) with

RD ≥ 1.5 mm)

Goal

Complete Revascularization

Rodriguez AE et al, Current Cardiol Review, 2017, (in press)

Trials CABG PCI Complete

Revascularization

CABG

Complete

Revascularization

PCI

p

EAST 194 198 99% 75% 0.002

ARTS 605 600 84.1 70.5 % 0.001

ERACI 64 63 88% 51% 0.001

CABRI 513 541 82% 59% 0.001

RITA 501 510 97% 81% 0.003

MASS II 203 205 74% 41% 0.001

SYNTAX 897 903 63% 57% 0.005

ERACI II 225 225 85% 50% 0.002

BEST TRIAL 442 438 72% 51% <0.001

Completeness of revascularization in

randomized clinical trials.

Can we accept a

“Reasonable” incomplete

revascularization after PCI?

Are all incomplete

revascularization the

same?

Completeness of Revascularization after PCI

Rodriguez AE et al, Current Cardiol Reports 2017, (in press)

Trials N° pts Follow-up Cut-off RSS Primary Objective HR (CI 95%) p

Alidoosti M 760 One year > 5 MACCE (all-cause of

death, cardiac death,

non-fatal MI and TVR)

8.08 (3.2-19.7) <0.001

Khan R 243 In-Hospital ≥ 8 NACE (in-hospital death,

CHF, recurrent MI and

ACUITY – defined major

bleeding

3.82 (1.58-9.21) <0.000

1

Généreux P 454 Five years 4.5 +/- 6.9 All cause of mortality 4.13 (2.79-6.11) <0.000

1

Witberg G 148 Tree years ≤ 8 MACCE (death, MI,

repeat revascularization

and CVA)

3.62 (1.14-9.03) 0.014

Généreux P 2618 One year SIR # Mortality 0.60 (0.53-0.67) <0.000

1

Xu B 1851 One year rSS ## TVF (cardiac death,

target vessel MI,

ischaemia-driven TVR)

1.40 (1.08-1.82) 0.01

Residual SYNTAX score in

Clinical Trials

ERACI IV STUDY DESIGN

1917 PCI march 2013-feb 2014

233 patients with

multiple vessel CAD

and no clinical EC

EXCLUSION CRITERIA

Pregnancy

LVEF ≤ 35%

Recent STEMI (< 72 hs)

PCI with DES in intention to treat artery

Recent PCI (6 months)

Lesion diameter ≤ 2.5 mm

CRF, CI for DAPT, thrombocitopenia,

leukopenia

INCLUSION CRITERIA

ACS, SA or large area at myocardium at

risk

Significant CAD suitable for PCI or CABG

ULMD

2 or 3 vessel disease

Lesions ≥ 70% by visual estimation

225 pts with PCI with

Rapamycin Chromium

Cobalt 2nd generation

DES

8 pts excluded

didn´t met angio criteria

PRIMARY END

POINT

MACCE

VS ERACI III : 225 pts 1° DES generation

(Taxus/Cypher)

Haiek C, Rodriguez AE et al. Catheter Cardiovasc Interv. 2016 Mar 7

PCI Strategy Operator Advices

Stent severe (≥70%) stenosis only.

Provisional stent strategy in all bifurcations.

Avoid stent in SB < 2.0 mm.

Complete Functional Revascularization.

Prasugrel or ticagrelor in diabetics, complex left

main or high SYNTAX score.

ERACI IV

Modifying angiographic syntax score according to PCI

strategy: lessons learnt from ERACI IV Study

Rodriguez AE et al. Cardiovasc Revasc Med. 2015 Oct-Nov;16(7):418-20.

YES.

-Guided

-Severe stenosis (≥ 70%) with

RD ≥ 2.0 mm)

NO.

-Intermediate lesions (50-69%)

-Severe lesions in vessels with

RD < 2 mm

GOAL: Functional

Revascularization

Rodriguez AE et al. Cardiovasc Revasc Med. 2015 Jul 11.(15)00182-7

Classical SYNTAX score and Modified by ERACI IV Syntax

score comparison from ERACI IV trial population.

PT ID:01-082

SYNTAX score=37 (Red & blue arrows) 7 DES

Modified ERACI IV SYNTAX score=31 (Red arrows) 3 DES

Rodriguez AE et al. Cardiovasc Revasc Med. 2015 Oct-Nov;16(7):418-20.

2.2 3.1

1.3

4.4

0.4

3.1

9.3

3.6 4.0

11.6

6.7

16.9

0.9

3.1

0.56 0.04 0.07 0.01 0.17 0.001 0.003 20

18

16

14

12

10

8

6

4

2

Death AMI CVA D/MI/CVA TVR MACCE Stent

thrombosis

ERACI III vs ERACI IV Events progression comparison at 2 years of follow-up

Two years follow-up

Haiek C, Rodriguez AE et al. Catheter Cardiovasc Interv. 2016 Mar 7 (ahead of print)

Rodriguez AE et al Minerva Cardioangiologica, 2017 in press

En Resumen como “take home message”

de esta revisión, las estenosis intermedias

(50 a 69%) o lesiones severas en vasos

pequenos, no deben incorporarse en la

estrategia de revascularización y del

implante de stent durante la PCI o

igualmente si quisiéramos por esto definir

en nuestros pacientes pronostico clinico

o “completeness “ de revascularización

obtenida luego de PCI.

PCI vs CABG en Mala FVI

Meta-analisis de 10 RCT entre PCI vs CABG, Hlatky et al Lancet 2009 yJACC 2010, mostraron que CABG y PCI tuvieron similar sobrevida en pacientes con mala funcion ventricular izquierda aunque solo pocos pacientes de estas caracteristicas fueron incluidos (FE<35%).

El estudio STICH entre CABG vs tratamiento medico no mostro diferencias significativas entre ambas estrategias en el punto final primario de mortalidad por todas las causa aunque en un analisis secundario redujo la mortalidad cardiovascular con relacion al TM (NEJM 2011).

Bangalore S et al Circulation 2016,133

Bangalore S et al Circulation 2016,133

Bangalore S et al Circulation 2016,133

Bangalore S et al Circulation 2016,133

Bangalore S et al Circulation 2016,133

Randomized clinical trials, PCI vs CABG, poor left

ventricular function,stents, DES, multiple vessels

etc etc in Medline/PubMed

= Items not found !!

PCI vs CABG en Mala FVI

Conclusion

• El uso de Score de Riesgo Funcionales ya sea mediante la utilizacion de mediciones Funcionales durante la PCI como FFR, la valoracion clinica funcional del paciente previo al procedimiento y/o la utilizacion de un analisis critico de las lesiones coronarias, Score de riesgo ERACI IV, considerando solo lesiones severas en vasos importantes, permiten una estrategia mas racional y conservadora durante la angioplastia evitando la implantacion innecesaria de multiples stents en comparacion al uso de Score de riesgo puramente anatomicos como el Syntax original.

• Lo anterior conjuntamente con el uso de 2da generacion de DES es lo que podria explicar los resultados sorprendentemente bajos a dos años de eventos cardiacos adversos incluyendo muerte/IAM/ACV demostrado en el estudio ERACI IV( 6.7% y 3.6% respectivamente) hallazgo que tambien fue observado en el subgrupo de pacientes diabeticos (5.8% y 1.4% respectivamente).

Muchas Gracias!!

PCI

STRATEGY

Non-Guided

SYNTAX Guided?

• FFR

• New scoring

ERACI III ERACI IV P value ERACI III ERACI IV P value

Age 65.5 +/-

10.6

63.9 +/- 11.2 0.06 65.1 +/- 9 64.3 +/- 9 0.50

Sex 83.6 85.6 0.89 75.9 82.4 0.24

Previous myocardial

infarction

32.4 33.3 0.68 35.2 37.0 0.77

Diabetes mellitus 20.9 30.7 0.02 30.6 28.7 0.76

Previous revascularization 22.7 34.7 0.007 29.6 35.2 0.38

High blood pressure 79.6 78.7 1.00 88.0 90.7 0.50

High cholesterol 79.1 66.7 0.04 82.4 69.4 0.02

Peripheral vascular

disease

11.6 6.7 0.07 9.3 5.6 0.29

Unstable angina IIb/IIIc 40.7 64.2 <0.001 60.2 71.2 0.77

Left main disease (LMD) 5.8 9.8 0.11 6.4 10.1 0.29

3 vessel CAD+LMD 38.2 54.3 0.003 39.8 56.5 0.01

N° stents per patient 1.79+/- 0.7 1.8 +/- 0.9 0.8 1.83 +/-

0.8

1.8 +/- 0.8 0.7

Baseline demographic, clinical, angiographic and procedural characteristics

Overall population and after matching results.

PROPENSITY SCORE (n=216) ERACI

III

ERACI

IV RR (CI 95%)

Sig

level

Any cause of death (%) 3.7 0.9 0.25 (0.02 to 2.20) 0.21

Myocardial infarction (%) 5.6 0.9 0.16 (0.02 to 1.36) 0.09

Non-fatal CVA (%) 1.9 0.0 0.2 (0.009 to 4.11) 0.29

Death/Myocardial Infarction/CVA (%) 8.3 1.9 0.22 (0.04 to 1.00) 0.05

Unplanned revascularization (%) 12.0 2.8 0.23 (0.06 to 0.78) 0.01

MACCE (Death/Myocardial infarction/CVA/TVR) (%) 16.7 3.7 0.22 (0.07 to 0.6) 0.005

Haiek C, Rodriguez AE et al. Catheter Cardiovasc Interv. 2016 Mar 7

24.5 +/- 3.8 months of follow-up results from ERACI IV study. Diabetic vs

non-diabetic subgroup analysis

Cummulative outcome of hard clinical events and primary endpoint.

Haiek C, Rodriguez AE et al. Catheter Cardiovasc Interv. 2016 Mar 7

37.5%

71.4%

0.09

ERACI I - 1993 17.7%

33.3%

0.02

ERACI II - 2001

9.0%

23.4%

0.006

ERACI III - 2006

7.0%

5.8%

0.9

ERACI IV - 2016

30 Years Journey of PCI in Multiple Vessels

CAD: Insights from ERACI I to IV Studies

Zero ST beyond

1st year

Summary First, the use of new generation DES plus guided PCI

strategy allowed to treat around 80% of patients with complex MVD/LM taking in account that less than 20% of these patients using “Functional “ (FFR or ERACI) scores are included at high SS.

Secondly in the ERACI IV study we observed at two years a remarkable low MACCE rate, just as lower rates for all individual components of the end points.

Third, low events rate was also seen in Diabetic patients and this was an unique finding in all ERACI studies previously conducted in the last 30 years.

Finally, this new Angiographic Risk Score appears to be useful to guide PCI operators during stent implantation and it was validated by low cardiac events and TLR rate at 2 years in treated and non treated lesions.

Take Home Message

Better DES design is not the solely goal to improve

outcome after PCI. In spite of different DES

designs, many RCT share similar PCI

strategy(Syntax, FREEDOM,BEST etc) including stenting all intermediate lesions (<70%) and small

vessels (<2.0mm).

To narrowing the gap between PCI and CABG in

future RCT we should need together with safe DES

designs incorporate new PCI strategies avoiding unnecessary DES implantation.

Limitations

Patients treated with 2nd generation DES were prospectively included years later than those treated with the first generation ones, and during those years, significant improvement in medical therapies have been introduced, in fact ERACI IV patients with complex CAD were under more active P2Y12 such as prasugrel or ticagrelor.

Secondly it is clear that FFR is the most accurate tool to assess functional revascularization strategy and lesion assessment .FFR was not used in this

study, also, is well known that incomplete revascularization were linked with poor outcome after PCI, however, long term outcome of those patients with incomplete anatomical or functional revascularization would be different if the residual non-treated lesions were intermediate or critical.

Finally, baseline clinical and angiographic characteristics between both groups were not equal, although all differences associated with poor outcome during PCI are more frequently present in ERACI IV, moreover, low MACCE rate in patients treated with 2nd generation DES remained after a matched propensity score was performed.

Mensaje para la

Audiencia

Antes y /o durante la PCI electiva evaluar funcionalmente al paciente y o a la lesion parece ser

mandatorio !! = Guided PCI

Abdalla et al. JAMA. 2013;310(15):1581-1590.