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Page 1: Drug-Eluting Stents for Multivessel PCI

Ajay J. Kirtane, MD, SM

Center for Interventional Vascular TherapyColumbia University Medical Center /

New York Presbyterian Hospital

Drug-Eluting Stents for

Multivessel PCI:

Indications and Outcomes

Page 2: Drug-Eluting Stents for Multivessel PCI

Conflict of Interest Disclosure

• Ajay J. Kirtane

None

Off-label use will be discussed

Page 3: Drug-Eluting Stents for Multivessel PCI

Two Goals of Therapy in

Patients with Stable CAD

1. Improve Symptoms and Quality

of Life

Measured by “soft endpoints”

(i.e. angina/QOL scales)

2. Improve Prognosis

Measured by “hard endpoints”

(i.e. death, MI)

Page 4: Drug-Eluting Stents for Multivessel PCI

It is generally accepted that

revascularization makes symptomatic

patients feel better… but it is also a

FACT that The Presence of Severe CAD

is Prognostically Important!

• Let’s not forget our History…

Workload / Exercise Tolerance

Burden of Disease / Ischemia

Patients with prior MI / Decreased

Ventricular Function may have

even more to gain / or lose

Page 5: Drug-Eluting Stents for Multivessel PCI

Meta-Analysis of CABG vs. Medical

Therapy: 7 RCTs

Yusuf S et al, Lancet 1994

Mo

rta

lity

Page 6: Drug-Eluting Stents for Multivessel PCI

6.7%

3.7%3.3%

1.0%

2.9%

4.8%

1.8% 2.0%

0%

2%

4%

6%

8%

10%

Medical Rx Revasc

Mitigatated Gradient with Revasuclarization

% Total Ischemic Myocardium

1- 5% 5-10% 11-20% >20%

Card

iac D

eath

Rate

1331 56 718 109 545 243 252 267

P <.0001

Hachamovitch et al Circulation. 2003;

107:2900-2907.

Page 7: Drug-Eluting Stents for Multivessel PCI

MPS % Ischemic Myocardium

(95% CI) Pre-Rx & 6-18 Months

0

40

5

10

15

20

25

35

30

Pre-Rx 6-18m

8.2%5.5%

(4.7%-6.3%)

PCI + OMT (n=159) OMT (n=155)

0

40

5

10

15

20

25

35

30

Pre-Rx 6-18m

(6.9%-9.4%)

8.6% 8.1%

Mean = -2.7%(95% CI = -3.8% to -1.7%)

Mean = -0.5%(95% CI = -1.6% to 0.6%)

p<0.0001

Shaw, et al, AHA 2007 and Circulation 2008

Page 8: Drug-Eluting Stents for Multivessel PCI

• Less progression to decreased

ventricular function / ischemic

cardiomyopathy

• Better tolerance of events in other

coronary distibutions

• Altered rheology within target vessel

• Less occlusion?

Why Could Revascularization of Higher-

Risk Ischemic Territories Be Important?

Page 9: Drug-Eluting Stents for Multivessel PCI

385 assigned

to OMT

BARI 2D: Patient Flow

378 assigned

to CABG

807 assigned

to OMT

798 assigned

to PCI

2368 pts were enrolled

763 were selected for

CABG vs. OMT

1605 were selected for

PCI vs. OMT

Coronary angiography in

pts with type 2 diabetes

IP = insulin provision

IS = insulin sensitization

Exclusions:

Revasc not indicated

Imm. revasc required

LM disease

S. Cr. >2.0 mg/dL

HgbA1C >13.0%,

Cl III or IV HF

Hepatic dysfunction

PCI or CABG w/i 1 yr

A study of prophylactic revascularization among patients

with no “definite need for invasive intervention”

The BARI 2D Study Group.

NEJM 2009;360:2503-15

Page 10: Drug-Eluting Stents for Multivessel PCI

BARI 2D: CABG Stratum

Survival Freedom from MACE

(death, MI, or stroke)

Su

rviv

al

(%)

YearsE

ven

t-fr

ee S

urv

ival

(%)

Years

P=0.33

0 1 2 3 4 50

20

40

60

80Medical Therapy

Revascularization

83.6

86.4

N at Risk 763 734 718 692 586 333

100

P=0.01

0 1 2 3 4 50

20

40

60

80

Medical Therapy

Revascularization

69.5

77.6

N at Risk 763 668 634 568 421 230

100

The BARI 2D Study Group.

NEJM 2009;360:2503-15

Page 11: Drug-Eluting Stents for Multivessel PCI

BARI 2D: Who got Revascularized?PCI Stratum CABG Stratum p

N=1176 N=1192

USA 73.7% 41.4% <0.0001

Prior MI 30.1% 36.0% <0.05

Proximal LAD disease 10.3% 19.4% <0.05

Pts without prior procedures

N lesions ≥50% DS, mean 2.1± 1.5 3.6± 1.7 <0.0001

N lesions ≥70% DS, mean 0.8± 1.0 1.7± 1.3 <0.0001

N of diseased vessels <0.0001

- 0 4% 1%

- 1 41% 9%

- 2 36% 37%

- 3 19% 53%

Any total occlusions 7% 14% <0.0001

Jeopardy index, % 38 ± 22 61 ± 21 <0.0001

The BARI 2D Study Group. NEJM 2009;360:2503-15

Schwartz L et al. AJC 2009;103:632–638

Page 12: Drug-Eluting Stents for Multivessel PCI

Ischemia-Eligible Stable Patient

(Stable CAD, Moderate-Severe Ischemia)

Blinded Coronary CTA

Eligible Anatomy?

RANDOMIZE

Invasive Strategy

(Cath with

Optimal Revasc + OMT)

CT Exclusion

Ancillary Study

OMT Strategy

(OMT Alone)

YESNO

ISCHEMIA Trial Proposed Design

J. Hochman, TCT 2010

Page 13: Drug-Eluting Stents for Multivessel PCI

5-year D/MI/CVA PCI vs. CABG

16.7% vs. 16.9%, P=0.69

HR [95%CI] = 0.96 [0.79-1.16]

Days

Fre

ed

om

fro

m D

eath

,

Str

oke

an

d M

I (%

)

100

90

80

70

60

50

0 365 730 1095 1460 1825

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

Bare Metal Stents vs. CABG

CABG 83.1%

PCI 83.3%

4 randomized trials, 3,051 randomized pts,5-year follow-up (patient level pooled analysis)

PLR = 0.64

Page 14: Drug-Eluting Stents for Multivessel PCI

Hlatky et al, The Lancet 2009;373:1190-1197

10 RCTs 7812 Pts: CABG vs. PCI: No Difference in

Death and MI

CABG 3889 3767 3675 3415 3180 2693 1853 1609 1477

PCI 3923 3798 3709 3431 3205 2658 1828 1576 1452

Years of follow-up

Mo

rtality

(%

)

CABG

PCI

35

30

25

20

15

10

5

00 1 2 3 4 5 6 7 8

No. of patients*D

eath

or

myo

card

ial

infa

rcti

on

(%

)CABG 3695 3369 3269 3001 2763 2294 1501 1269 1161

PCI 3725 3419 3310 3023 2797 2267 1491 1253 1150

Years of follow-up

35

30

25

20

15

10

5

00 1 2 3 4 5 6 7 8

Page 15: Drug-Eluting Stents for Multivessel PCI

CABG vs PCI :Death and Diabetic Status

Number of patients*

CABG no diabetes 3263 3169 3089 2877 2677 2267 1592 1380 1274

CABG diabetes 615 587 575 532 498 421 257 225 200

PCI no diabetes 3298 3217 3148 2918 2725 2281 1608 1393 1288

618 574 555 508 475 373 218 179 160

Years of follow-up

Mo

rtali

ty (

%)

CABG no diabetes

CABG diabetes

PCI no diabetes

PCI diabetes

35

30

25

20

15

10

5

00 1 2 3 4 5 6 7 8

PCI diabetes

Hlatky et al, The Lancet 2009;373:1190-1197

Page 16: Drug-Eluting Stents for Multivessel PCI

71% enrolled

(N=3,075)

All Pts with de novo 3VD and/or

LM disease (N=4,337)

Treatment preference (9.4%)

Referring MD or pts. refused

informed consent (7.0%)

Inclusion/exclusion (4.7%)

Withdrew before consent (4.3%)

Other (1.8%)

Medical treatment (1.2%)TAXUS

n=903

PCI

n=198

CABG

n=1077CABG

n=897no f/u

n=4285yr f/u

n=649

PCIall captured w/

follow up

CABG2500

750 w/ f/uvs

Total enrollment N=3075

Stratification:

LM and Diabetes

Two Registry ArmsRandomized Armsn=1800

Two Registry ArmsN=1275

Randomized ArmsN=1800

Heart Team (surgeon & interventionalist)

PCI

N=198CABG

N=1077

Amenable for only one

treatment approach

TAXUS*

N=903CABG

N=897vs

Amenable for both

treatment options

Stratification:

LM and Diabetes

LM

33.7%3VD

66.3%

LM

34.6%3VD

65.4%

23 US Sites62 EU Sites +

SYNTAX Trial Design

* TAXUS Express

Page 17: Drug-Eluting Stents for Multivessel PCI

SYNTAX: All-Cause Death to 3 Years

Before 1 year*

3.5% vs 4.4%

P=0.37

TAXUS (N=903)CABG (N=897)

6.7%

8.6%

0 12 36

20

40

0

Months Since Allocation

Cu

mu

lati

ve

Eve

nt

Rate

(%

)

1-2 years*

1.5% vs 1.9%

P=0.53

2-3 years*

1.9% vs 2.6%

P=0.32

24

Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact Test

P=0.13

Page 18: Drug-Eluting Stents for Multivessel PCI

SYNTAX: All-Cause Death/CVA/MI to 3 Years

Before 1 year*

7.7% vs 7.6%

P=0.98

TAXUS (N=903)CABG (N=897)

12.0%

14.1%

0 12 36

20

40

0

Months Since Allocation

Cu

mu

lati

ve

Eve

nt

Rate

(%

)

1-2 years*

2.2% vs 3.5%

P=0.11

2-3 years*

2.5% vs 3.8%

P=0.14

24

Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact Test

P=0.21

ITT population

Page 19: Drug-Eluting Stents for Multivessel PCI

SYNTAX: MACCE to 3 Years

Before 1 year*

12.4% vs 17.8%

P<0.002

TAXUS (N=903)CABG (N=897)

20.2%

28.0%

0 12 36

20

40

0

Months Since Allocation

Cu

mu

lati

ve

Eve

nt

Rate

(%

)

1-2 years*

5.7% vs 8.3%

P=0.03

2-3 years*

4.8% vs 6.7%

P=0.10

24

Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact Test

P<0.001

ITT population

Page 20: Drug-Eluting Stents for Multivessel PCI

SYNTAX: Repeat Revascularization to 3 Years

Before 1 year*

5.9% vs 13.5%

P<0.001

TAXUS (N=903)CABG (N=897)

10.7%

19.7%

0 12 36

20

40

0

Months Since Allocation

Cu

mu

lati

ve

Eve

nt

Rate

(%

)

1-2 years*

3.7% vs 5.6%

P=0.06

2-3 years*

2.5% vs 3.4%

P=0.33

24

Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact Test

P<0.001

ITT population

Page 21: Drug-Eluting Stents for Multivessel PCI

SYNTAX: Generic QOL and Utilities

0.5

0.6

0.7

0.8

0.9

1

Baseline 1 month 6 months 12 months

30

40

50

Baseline 1 month 6 months 12 months

SF-36 Mental Component Summary

P=0.23 P=0.43

30

35

40

45

50

55

Baseline 1 month 6 months 12 months

P=0.50 P=0.07

P=0.16 P=0.99

SF-36 Physical Component Summary

EQ-5D Utilities (US)

PCI

CABG

0.5

0.6

0.7

0.8

0.9

1

Baseline 1 month 6 months 12 months

30

40

50

Baseline 1 month 6 months 12 months

SF-36 Mental Component Summary

P<0.001

30

35

40

45

50

55

Baseline 1 month 6 months 12 months

P<0.001

P<0.001

SF-

EQ-5D Utilities (US)

PCI

CABG

PCI

CABG

Page 22: Drug-Eluting Stents for Multivessel PCI

SAQ-AF: Angina-Free*

* Defined as SAQ-AF score = 100

SYNTAX · Health Economics/Quality of Life ACC 2009 · Orlando, FL · 32

71.6%76.3%

0%

20%

40%

60%

80%

100%

1 month 6 months 12 months

PCI CABG

P=NS

P=NSP=0.05

64.4%61.6%

68.5%72.0%

Page 23: Drug-Eluting Stents for Multivessel PCI

PCI and CABG Post-SYNTAX

• Each strategy can have great

outcomes in appropriately

selected patients

• Hard clinical outcomes

(death/MI/CVA) are generally similar

• Need to weigh the risk of potential

repeat procedures with PCI vs. the

greater morbidity of CABG

Page 24: Drug-Eluting Stents for Multivessel PCI

SYNTAX: One-year MACCE Rates by Site

CABG MACCE (%)

TA

XU

S S

ten

t M

AC

CE

(%

)

50

30

40

20

10

0

10 20 30 40 50

Size of circle adjusted for number of patients

Page 25: Drug-Eluting Stents for Multivessel PCI

MACCE to 3 Years by SYNTAX Score

Tercile Low Scores (0-22)

Mean baseline

SYNTAX Score

CABG 16.6 ± 4.0

TAXUS 16.7 ± 4.1

TAXUS (N=299)CABG (N=275)

22.5%

22.7%

0 12 36

20

40

0

Months Since Allocation

Cu

mu

lati

ve

Eve

nt

Rate

(%

)

24

Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact Test

P=0.98

Calculated by core laboratory;

ITT population

Page 26: Drug-Eluting Stents for Multivessel PCI

MACCE to 3 Years by SYNTAX Score

Tercile Intermediate Scores (23-32)

Mean baseline

SYNTAX Score

CABG 27.4 ± 2.8

TAXUS 27.3 ± 2.8

TAXUS (N=310)CABG (N=300)

18.9%

27.4%

0 12 36

20

40

0

Months Since Allocation

Cu

mu

lati

ve

Eve

nt

Rate

(%

)

24

Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact Test

P=0.02

Calculated by core laboratory;

ITT population

Page 27: Drug-Eluting Stents for Multivessel PCI

MACCE to 3 Years by SYNTAX Score

Tercile High Scores (>33)

Mean baseline

SYNTAX Score

CABG 41.5 ± 7.1

TAXUS 41.7 ± 7.8

TAXUS (N=290)CABG (N=315)

19.5%

34.1%

0 12 36

20

40

0

Months Since Allocation

Cu

mu

lati

ve

Eve

nt

Rate

(%

)

24

Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary ratesEvent Rate ± 1.5 SE. * Fisher’s Exact Test

P<0.001

Calculated by core laboratory;

ITT population

Page 28: Drug-Eluting Stents for Multivessel PCI

Indications for CABG vs PCI in stable patients with

lesions suitable for both procedures and low

predicted surgical mortality

Subset of CAD by anatomy Favours CABG Favours PCI

1VD or 2VD – non proximal LAD IIb C I C

1VD or 2VD – proximal LAD I A IIa B

3VD simple lesions, full functional revascularization

achievable with PCI, SYNTAX score ≤ 22I A IIa B

3VD complex lesions, incomplete revascularizarion

achievable with PCI, SYNTAX score > 22I A III A

Left main (isolated or 1VD, ostium/shaft) I A IIa B

Left main (isolated or 1VD, bifurcation) I A IIb B

Left main + 2VD or 3VD, SYNTAX score ≤ 32 I A IIb B

Left main + 2VD or 3VD, SYNTAX score ≥ 33 I A III B

ESC guidelines 2010

Page 29: Drug-Eluting Stents for Multivessel PCI

Pitfalls and issues relevant to SYNTAX

score application in clinical practice

Time-consuming, with Interobserver and intraobserver

variability

Does not account for clinical or procedural variables

that are known to impact outcomes during and after PCI

Underpowered outcomes based upon subgroup

analysis

Does not include any subset of lesions (i.e. in-stent

restenosis, stenotic bypass grafts, coronary anomalies,

muscular bridges, aneurysms)

Does not account for patient choice!

Capodanno, et al. Am Heart J 2011;161:462-70

Page 30: Drug-Eluting Stents for Multivessel PCI

In observational registries, the intermediate tertile is

frequently poorly calibrated with respect to the

outcomes of the high and low tertiles

32-month MACE

Brito et al.EuroPCR 2010

3-year MACCE

MAIN COMPAREJACC Interv 2010

SYNTAXCirculation 2010

1-year MACCE 1-year MACE

Capodanno et al.Circ Card Interv 2009

Expected risk for the intermediate stratum

+14.0%-11.2%

+6.5%

Capodanno, et al. Am Heart J 2011;161:462-70

Page 31: Drug-Eluting Stents for Multivessel PCI

Mortality with Complete vs.

Incomplete Revascularization in MVDCategorization by SYNTAX Score

Kim YH et al, Circulation 2011

Page 32: Drug-Eluting Stents for Multivessel PCI

FAME: Optimizing Complete

Revascularization

Tonino PAL et al. NEJM 2009;360:213–24

FFR-guided

(n=509)

30 days

2.9% 90 days

3.8% 180 days

4.9%360 days

5.3%

Angio-guided

(n=496)

Absolute difference in MACE-free survival

Days

Fre

ed

om

fro

m d

ea

th, M

I, r

eva

sc

0 60 120 180 240 300 360

0.70

0.75

0.80

0.85

0.90

0.95

1.00

MACE 13.3% vs. 18.2%

P=0.02

1005 pts with MVD undergoing PCI with DES were randomized to

FFR-guided vs. angio-guided intervention

Page 33: Drug-Eluting Stents for Multivessel PCI

3056029-1

Angiographic vs. Functional Severity of Coronary Stenosis

Of 509 pts with angiographically-defined MVD,

46% had “functional MVD”

FFR

50-70 71-90 91-99

Stenosis classification by angiography

~20%

~35%

Tonino et al, NEJM 2009

Page 34: Drug-Eluting Stents for Multivessel PCI

FAME : “Downgrading” Multivessel Disease

with FFR

9% 14%

43%

34%

3-VD

2-VD

1-VD

0-VD

43%

45%

12%

2-VD

1-VD

0-VD

3 Vessel Disease 2 Vessel Disease

Tonino et al, JACC 2010;55:2816-21

86% 3VD and 57% 2VD reclassified >1 vessel

Page 35: Drug-Eluting Stents for Multivessel PCI

Change in SYNTAX Score after FFR

166

(34%)

170

(35%)

160

(32%)

Lowest Tertile

Middle Tertile

Highest Tertile

CW Nam (preliminary data); presented TCT 2010

Without FFR

SYNTAX score ~500 FAME patients after FFR

281

(57%)

119

(24%)

95

(19%)

Lowest Tertile

Middle Tertile

Highest Tertile

With FFR

Page 36: Drug-Eluting Stents for Multivessel PCI

Stable Patient scheduled for

1, 2, or 3-vessel PCI

FFR in all stenoses

FFR≤0.80 in ≥1 lesion

RANDOMIZE (n=1600)

PCI + OMT

(Indicated stenoses)

OMT Alone

Registry

OMT Alone

YESNO

FAME II Study Design

W. Fearon, TCT 2010

Page 37: Drug-Eluting Stents for Multivessel PCI

SPIRIT II, III, IV and COMPARE trials

Pooled database analysis (n=6,789)

Ischemic TLR

P<0.001

HR: 0.60 [0.48, 0.75]EES (n=4,247)

PES (n=2,542)

4247 4143 4004 3363

2542 2416 2328 2018

Number at risk

XIENCE

TAXUS

6.6%

Isch

em

ic T

LR

(%

)

0

10

Time in Months

0 3 6 9 12 15 18 21 24

3891

2260

4.1%5 4.7%

2.3%

Page 38: Drug-Eluting Stents for Multivessel PCI

SPIRIT II, III, IV and COMPARE trials

Pooled database analysis (n=6,789)

Stent thrombosis (ARC definite/probable)

4247 4177 4082 3479

2542 2463 2408 2110

Number at risk

XIENCE

TAXUS

2.3%

Ste

nt

thro

mb

osis

AR

C d

ef

or

pro

b (

%)

0

1

2

3

Time in Months

0 3 6 9 12 15 18 21 24

3998

2350

0.7%

p<0.001

HR: 0.30 [0.19, 0.47]EES (n=4,247)

PES (n=2,542)

Page 39: Drug-Eluting Stents for Multivessel PCI

Potential SYNTAX MACCE with 2nd Gen DES

TAXUS (N=903)CABG (N=897)

20.2%

28.0%

0 12 36

20

40

0

Months Since Allocation

Cu

mu

lati

ve

Eve

nt

Rate

(%

)

24

Cumulative KM Event Rate ± 1.5 SE; log-rank P value; * Binary rates

Event Rate ± 1.5 SE. * Fisher’s Exact Test

P<0.001

ITT population

30%

Page 40: Drug-Eluting Stents for Multivessel PCI

Eligibility: DM patients with MV-CAD eligible for stent or surgeryExclude: Patients with acute STEMI, cardiogenic shock

MV DES stenting(Cypher or TAXUS)

and abciximab

CABG with or withoutcardiopulmonary

bypass

PRIMARY Endpoint: 3-year death, MI, stroke

SECONDARY Endpoints: 12-month MACCE, 3-year Quality of Life

N=1900 at 100 centers from NA, SA, EU, Rand. 1:1

PI: Valentin Fuster

FREEDOM Trial (NHLBI)

Page 41: Drug-Eluting Stents for Multivessel PCI

Key Decision Points in Multivessel

Revascularization

• What are the goals of therapy?

• Can the patient take/adhere to DAPT?

• Is the patient high surgical risk?

• Is the patient insulin dependent?

• WHAT DOES THE PATIENT WANT?

Page 42: Drug-Eluting Stents for Multivessel PCI

Conclusions: Multivessel Disease

• These are high-risk coronary lesions and the

least stable subtypes of “stable CAD”

• PCI and CABG have very similar rates of

“hard” clinical endpoints and Sx/QOL will

largely depend on completeness of revasc

Greater rates of repeat revascularization with PCI,

especially in complex disease

• Patient selection and patient preference will

generally dictate the best and most

appropriate care!