the best strategy for the patient with multivessel coronary artery disease claudio moretti, md...

The best strategy for the patient with multivessel coronary artery disease

Claudio Moretti, MD

CARDIOLOGIA INTERVENTISTICA - UNIVERSITA’ DI TORINOOSPEDALE S.G.BATTISTA “Molinette”


The debate is an anglosaxon concept. In The debate is an anglosaxon concept. In

general, debates are a waste of time and general, debates are a waste of time and

energy and are close to an exercise in futility. energy and are close to an exercise in futility.

However, debates keep the audience However, debates keep the audience

entertained by artificially discussing issues entertained by artificially discussing issues

which are going to be resolved spontaneously.which are going to be resolved spontaneously.

P. SerruysP. Serruys

PRELIMINARIES


OVERVIEW

4

• Trial

• Clinical Parameters

Angiographic Endpoints

Cost AssessmentMortality & MI Angina Relief

Repeat Revasculariza

tion

GABI PCI PCI CABG No difference n/a

EAST No difference CABG CABG CABG PCI

RITA No difference CABG CABG n/a n/a

ERACI No difference CABG CABG n/a PCI

CABRI No difference CABG CABG n/a n/a

BARI No difference n/a CABG n/a n/a

MASS-2CABG (MI) n/a CABG n/a No

difference

AWESOME No difference No difference CABG n/a n/a

ERACI-2PCI n/a CABG CABG No

difference

SoS CABG (Mortality) CABG CABG n/a n/a

ARTS No difference n/a CABG n/a PCI

Superior Treatment ModalityNo stents used

Stents used CABG No differencePCI


Previous POBA studies Meta-analysis

3300 patients1660 CABG, 1710 PTCA Deaths 79 PCI vs 73 CABGRevascularisation rates 33% PCI v 3% CABG

Pocock SJ, et al. Lancet 1995

Unbiased estimate for patients who meet the (strict) entry criteria

< 5 % pts randomized

3

5,8

1,1

18

24

2,81,5

4,4

13

5,5

0

5

10

15

20

25

30

Death MI

Stroke

re-interventio

n

Total MACE

PCI

CABG

One-year outcomes of CABG vs PCI in multvessel disease: Meta-analysis from randomized clinical trials ( ARTS I , SoS, ERACI II, MASS II )

PCI 1518 pts vs CABG 1533 pts (1995-2000)

( Pts with LM disease , poor LV function and diffuse disease excluded )

All cause mortality at one yearCABG PCI

Numbers at risk

PCI 1518 1484 1472

CABG 1533 1501 1490

1476

1495

4

2

0

3

0

Cu

mu

lati

ve e

ven

t ra

te (

%)

1

120 360240

Days after randomization

Adjusted HR* (95% CI) = 1.02 (0.64 – 1.60)

3.0

2.8

Mercado N, Wijns W, Serruys PW, et al. J Thorac Cardiovasc Surg 2005; 130.


CONCLUSIONS At five years there was no difference in mortality between stenting and surgery for multivessel

　　　　　　　 disease. Furthermore, the incidence of stroke or myocardial infarction was not significantly

different between the two groups. However, overall MACCE was higher in the stent group,

driven by the increased need for repeat revascularization. (J Am Coll Cardiol 2005;46:

575–81)

CONCLUSIONS At five years of follow-up, in the ERACI II study, there were no survival benefits from any

revascularization procedure; however patients initially treated with CABG had better freedom

from repeat revascularization procedures and from MACE. (J Am Coll Cardiol 2005;46:

582–8)


Superior Treatment Modality

Registries• Broad Inclusion• Stent selection by the Operator

discretion • Large populations > 2000 • Usually multi center• Less adjusted required

propensity score• Clinical follow-up only• Reflect more “real world”

experience

Randomized Trials• Restricted inclusion with broad

exclusion criteria• Small sample size < 1500• Limited centers participate• Includes angio follow-up • Always clinical follow up in the

office• More experienced centers• Monitoring and adjudication of all

cases

Registries Versus Randomized Clinical Trials

Draft of Correspondence to NEJM Letter to the editors (never submitted ! )Letter to the editors (never submitted ! )

“This observational report attempts to equalize

the two groups by using risk-adjusted survival

methods. This flawed methodology attempts to

adjust an unadjustable characteristic:

– the judgment of the treating physician

regarding the revascularization strategy that is

not correctable by adjusting for clinical variables.”

Ong, Serruys, Boersma (August Ong, Serruys, Boersma (August 2005)2005)

ARTS II – Study designARTS II – Study design

Primary endpoint:Primary endpoint: effectiveness of coronary stent implantation effectiveness of coronary stent implantation using the using the CYPHERCYPHER®® S Sirolimus-eluting Stent with that of surgery as irolimus-eluting Stent with that of surgery as observed in ARTS Iobserved in ARTS I measured as MACCE-free survival at 1 year. measured as MACCE-free survival at 1 year.

ARTS IIARTS II CYPHER® StentCYPHER® Stent

N=N=607607

ARTS IARTS I

CABGCABG

N= 605N= 605

CrownCrown™ Stent™ Stent

N= 600N= 600

RR

• Same inclusion / exclusion criteria

• Same MACE definition.

Serruys PW et al; EuroInterv 2005; 1: 147-56

ARTS II - MACCE up to 1 yearARTS II - MACCE up to 1 year

93.6%93.6%

80.2%80.2%

91.0%91.0%

96.9%96.9%

90.8%90.8%93.8%93.8%

Time (Days)Time (Days)

0 50 100 150 200 250 300 350 4000 50 100 150 200 250 300 350 400

Eve

nt f

ree

Sur

viva

l (%

)E

vent

fre

e S

urvi

val (

%) 1010

00 9595 9090 8585 8080 7575 7070 6565 60 60 - ARTS II- ARTS II

- ARTS I CABG- ARTS I CABG- ARTS I PCI- ARTS I PCI P (log rank) =0.46 between P (log rank) =0.46 between

ARTS IIARTS II and and ARTS I-CABGARTS I-CABG

89.5%89.5%

73.7%73.7%

88.5%88.5%

Serruys PW et al; EuroInterv 2005; 1: 147-56

“The Rosy Prophecy “


Anatomy Severity

Patient

MVD : heterogeneous entity

Euro Heart Survey on PCI

Multivessel disease ….

Focal lesions

Multivessel disease ….

Tortuosity

Thrombus

Bifurcation Total Occlusion

3 Vessel

Left Main

Lesion location

Calcification

Scoringsystem

SYNTAX (SYNergy between PCI with TAXUS and cardiac surgery)

Post – ESC , Munich 2008

Limited Exclusion CriteriaPrevious interventions (PCI or CABG)Acute MI with CPK>2xConcomitant valve surgery

SYNTAX Score• Anatomic Scoring• For Each Lesion Segment

– Location– Length– Calcification– Tortuosity– Bifurcation– Diffuse Disease– Occlusion– Thrombus

SYNTAX Score

SYNTAX Score = 18 SYNTAX Score = 41

Primary Endpoint: Randomized trial

The primary clinical endpoint is the 12-Month binary MACCE rate. MACCE* is defined as:

All cause Death

Cerebrovascular Event (Stroke)

Documented Myocardial Infarction

Repeat Revascularization (PCI and/or CABG)

The primary endpoint (12-month MACCE) will be analyzed for all patients as well as the subgroups of patients with 3VD only and patients with LM disease.

SYNTAX

*ARC MACCE definition Circulation 2007; 115:2344-2351

Final Enrollment DataEnrollment Completed April 2007

TotalEnrollment

N=3075

Greater Lesion Complexity

•Chronic totalocclusions

•Diffuse coronary disease

More Comorbities

Compassionate use

23North American

62 European

SitesRandomized

N=1800

CABGN=1077

PCI N=198

Presented by P. Serruys, MD - EuroPCR 2007

What can we conclude from SYNTAX Trial ?

In patients with MVD ( including patients with LM disease):

Equivalence in safety overall outcomes (Death, MI, CVA) in PCI and CABG patients ( 7.7% vs 7.6 %)

Significant higher rates of TLR / TVR in PCI patients (13.7 % vs 5.9% )

Significant higher rates in CVA in CABG patients (2.2% vs 0.6%)

Similar symptomatic gratf occlusion and stent thrombosis at 12 months

What can we conclude from SYNTAX Trial ?

Only 65% of patients with MVD are amenable for PCI

Surgery is not the only option for unprotected LMCA disease

Need for patients’ startification for the appropriate revacularization option ( SYNTAX Score ? )

Need for a longer follow up data

How will the results of the SYNTAX study impact your practice on patients with multivessel disease and

unprotected LM?

• More CABG 22 %• More PCI with DES 39 %

• Will not change 39 %

22

39

39

More CABG

More PCI with DES

Will not cahnge

From: www.CRTonline.org September 2008

http://www.crtonline.org/

http://www.crtonline.org/


Multivessel PCIMultivessel PCI

...my personal opinion...my personal opinion


MVD : focal lesions

DES!

Safe and effective treatment.....

Two days later…..

24 h post multivesselPCI


MVD : diffuse disease

….

Surgery Has Changed !!

Adverse events from CAGs… Adverse events from CAGs… in contemporary practice in contemporary practice

Graft occlusion in 2007…. Graft occlusion in 2007….

Multivessel PCI in 2008 : For unselected patients, MV PCI with DES is a safe

option but remains associated with an increased need for repeat procedures compared to surgery

Appropriate patient selection (risk scoring, medication compliance, co-morbidities) and revascularization strategy (single session vs staging, complete vs partial revascularization, etc) continue to play a critical role

To compete effectively with surgical revascularisation where SYNTAX has shown equvalnce we must ensure:- complete revascularisation- optimal stent expansion- minimise myocardial injury

Angiography-guided PCI FFR-guided PCI

Measure FFR in all indicated stenoses

Stent all indicated stenoses

Stent only those stenoses with FFR ≤ 0.80

Randomization

Indicate all stenoses ≥ 50% considered for stenting

Patient with stenoses ≥ 50% in at least 2 of the 3 major

epicardial vessels

1-year follow-up

FLOW CHART

FFR-guided

30 days2.9% 90 days

3.8% 180 days4.9% 360 days

5.3%

Angio-guided

absolute difference in MACE-free survival

FAME study: FAME study: Event-free Survival Event-free Survival

FAME study: FAME study: CONCLUSIONS (1)CONCLUSIONS (1)

Routine measurement of FFR during PCI with DES Routine measurement of FFR during PCI with DES in patients with multivessel disease, when in patients with multivessel disease, when compared to current angiography guided strategycompared to current angiography guided strategy

• reduces the rate of the composite endpoint of reduces the rate of the composite endpoint of

death, myocardial infarction, re-PCI and CABG death, myocardial infarction, re-PCI and CABG

at 1 year by ~ 30%at 1 year by ~ 30%

• reduces mortality and myocardial infarction at reduces mortality and myocardial infarction at

1 year by ~ 35 %1 year by ~ 35 %


Superior Treatment ModalityTHANKS …for Your attention !

FAME study: FAME study: BACKGROUND (1)BACKGROUND (1)

• Stenting of non-ischemic stenoses has no benefitStenting of non-ischemic stenoses has no benefit compared to medical treatment onlycompared to medical treatment only

• Stenting of ischemia-related stenoses improvesStenting of ischemia-related stenoses improves symptoms and outcomesymptoms and outcome

• In multivessel coronary disease (MVD), identifyingIn multivessel coronary disease (MVD), identifying which stenoses cause ischemia is difficult:which stenoses cause ischemia is difficult: Non-invasive tests are often unreliable in MVD andNon-invasive tests are often unreliable in MVD and coronary angiography often results in both under- coronary angiography often results in both under- or overestimation of functional stenosis severityor overestimation of functional stenosis severity

0.070.0729 (5.7)43 (8.7)All myocardial infarctionsAll myocardial infarctions

1727Other infarctions (“late or large”)Other infarctions (“late or large”)

Events at 1 year, No (%)Events at 1 year, No (%)

1216Small periprocedural CK-MB 3-5 x NSmall periprocedural CK-MB 3-5 x N

Myocardial infarction, specifiedMyocardial infarction, specified

0.020.0276113Total no. of MACETotal no. of MACE

0.080.0833 (6.5)47 (9.5)CABG or repeat PCICABG or repeat PCI

0.040.0437 (7.3)55 (11.1)Death or myocardial infarctionDeath or myocardial infarction

0.190.199 (1.8)15 (3.0)DeathDeath

0.020.0267 (13.2)91 (18.4)Death, MI, CABG, or repeat-PCIDeath, MI, CABG, or repeat-PCI

P-valueP-valueFFR-group

N=509

ANGIO-group

N=496

FAME study: FAME study: Adverse Events at 1 yearAdverse Events at 1 year

0.070.07360 (73)326 (68)Patients without event and free Patients without event and free

from anginafrom angina

0.200.20399 (81)374 (78)Patients free from angina, No. (%)Patients free from angina, No. (%)

0.480.481.2 ± 0.81.2 ± 0.7Number of anti-anginal meds, No.Number of anti-anginal meds, No.

0.650.6575 ± 1674 ± 16EQ-5D visual analogue scaleEQ-5D visual analogue scale

P-valueP-valueFFR-group

N=509

ANGIO-group

N=496

FAME study: FAME study: Functional Class at 1 Year Functional Class at 1 Year


Routine measurement of FFR during PCI with DES Routine measurement of FFR during PCI with DES in patients with multivessel disease, when in patients with multivessel disease, when compared to current angiography guided strategy,compared to current angiography guided strategy,furthermore:furthermore:

• is cost-saving and does not prolong the procedureis cost-saving and does not prolong the procedure

• reduces the number of stents usedreduces the number of stents used

• decreases the amount of contrast agent useddecreases the amount of contrast agent used

• results in a similar, if not better, functional statusresults in a similar, if not better, functional status

Routine measurement of FFR during DES-stenting Routine measurement of FFR during DES-stenting in patients with multivessel disease is superior in patients with multivessel disease is superior to current angiography guided treatment.to current angiography guided treatment.

It improves outcome of PCI significantlyIt improves outcome of PCI significantly

It supports the evolving paradigm of It supports the evolving paradigm of

“ “Functionally Complete Revascularization”,Functionally Complete Revascularization”, i.e. stenting of ischemic lesions and i.e. stenting of ischemic lesions and medical treatment of non-ischemic ones.medical treatment of non-ischemic ones.


Multivessel stenting is off label……. Multivessel stenting is off label……. but…….but…….

68 yrs oldStable anginaNot diabeticNormal LV3 vessel disease

SYNTAX score 15

Can we do it ?Can we do it ?

FREEDOM Trial

Future REvascularization Evaluation in patients with Diabetes mellitus: Optimal management of

Multivessel disease

Multivessel PCI - ConclusionsMultivessel PCI - Conclusions For selected patients, MVPCI with BMS is a safe option For selected patients, MVPCI with BMS is a safe option

but remains associated with an increased need for repeat but remains associated with an increased need for repeat procedures compared to surgeryprocedures compared to surgery

The use of DES appears to be associated with MACCE The use of DES appears to be associated with MACCE rates similar to those of surgery, despite a stent thrombosis rates similar to those of surgery, despite a stent thrombosis rate per patient that is probably higher than for single rate per patient that is probably higher than for single vessel proceduresvessel procedures

The pivotal RCT’s of DES vs CABG are still ongoingThe pivotal RCT’s of DES vs CABG are still ongoing

Appropriate patient selection (risk scoring, medication Appropriate patient selection (risk scoring, medication compliance, co-morbidities) and revascularization strategy compliance, co-morbidities) and revascularization strategy (single session vs staging, complete vs partial (single session vs staging, complete vs partial revascularization, etc) continue to play a critical role revascularization, etc) continue to play a critical role

ConclusionConclusion

Our preliminary results provide evidence that the Syntax Our preliminary results provide evidence that the Syntax score may become a suitable tool to risk-stratify early and score may become a suitable tool to risk-stratify early and late outcome in patients with 3VD.late outcome in patients with 3VD.

Patients with the Syntax score greater than 26 (31?) may Patients with the Syntax score greater than 26 (31?) may be better treated with surgical revascularization. be better treated with surgical revascularization.

The Syntax study will confirm whether the Syntax score of The Syntax study will confirm whether the Syntax score of 26 is a discriminating criteria to select patients who should 26 is a discriminating criteria to select patients who should be treated by either surgery or DES. be treated by either surgery or DES.

So far, two third (score < 26) of the ARTS II patients with So far, two third (score < 26) of the ARTS II patients with 3VD have an excellent outcome. 3VD have an excellent outcome.

CONCLUSIONS

CABG will remain the Gold Standard until PCI has long term data that is better

Despite sicker patients, CABG results have uniformly improved – STS

Resource utilization for CABG has dramatically decreased

Off pump surgery can provide complete revascularization at lower risk and cost

Aggressive use of statins and life style changes will improve results of both therapies

Aggressive treatment for LDL and soon HDL will diminish both surgical and catheter interventions


Length is no longer Length is no longer important or is it?important or is it?


Incomplete expansion Incomplete expansion remains a major cause remains a major cause of stent thrombosisof stent thrombosis

Incomplete expansion Incomplete expansion of DES is a major of DES is a major cause of stenosis and cause of stenosis and therefore therefore re-re-stenosisstenosis

Issues in MVD (3) Issues in MVD (3) Calcification - limiting stent expansionCalcification - limiting stent expansion

Not all MVD patients are born equal ……..

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• Complete revascularizationComplete revascularization

• Long stents - Procedural MILong stents - Procedural MI

• Calcification – limiting stent expansionCalcification – limiting stent expansion

Key issues in MVD PCI

24 h post multivesselPCI

24 h post CABG

Slide AcknowledgementsSlide Acknowledgements

K DawkinsK Dawkins

P UrbanP Urban

L Testa & team at JRL Testa & team at JR

ARTS II ARTS II -- Study designStudy design

•• Single arm, Single arm, multicentermulticenter trialtrial

•• 607 patients in 45 centers607 patients in 45 centers from 19 countriesfrom 19 countries

•• The main goal of the ARTS II trial is to demonstrate The main goal of the ARTS II trial is to demonstrate nonnon--inferiority in clinical effectiveness and costinferiority in clinical effectiveness and cost--effectiveness with the CYPHEReffectiveness with the CYPHER®® stentstent compared to compared to the previous results of the ARTS I trialthe previous results of the ARTS I trial

ARTS IIARTS II

CABGCABG

N= 605N= 605

CROWNCROWN™™ & & CrossFlexCrossFlex LCLC™™

N=600 N=600

ARTS IARTS I

RandomizationRandomization

CYPHERCYPHER®®

N= 607N= 607

There is ‘3-vessel disease’ and ‘3-vessel disease’.

Patient 1

Patient 1 Patient 2

Patient 2

the best strategy for the patient with multivessel coronary artery disease claudio moretti, md...

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