Angioplasty Summit, TCTAPS l A il 25th 2012Seoul, April 25th 2012

Advances and Future in PCI 

Stephan WindeckerStephan Windecker

Department of CardiologyDepartment of Cardiology

Swiss Cardiovascular Center and Clinical Trials Unit Bern

Bern University Hospital, Switzerland

Scientific Advances and Cardiovascular MortalityCardiovascular Mortality

Nabel and Braunwald. N Engl J Med 2012;366:54‐631958

CoronaryCoronaryarteriographydeveloped(Sones)

2002Efficacy ofdrug‐elutingvs. bare‐

19771977Coronary

angioplasty

vs. baremetal stentsdetermined

developed(Grüntzig) 1993

Superiority ofprimary PCI vsprimary PCI vs. fibrinolysis in acute MI noted

MortalityMortality andand Repeat Repeat RevascularizationRevascularization withwithEarly Generation DES versus BareEarly Generation DES versus Bare MetalMetal StentsStentsEarly Generation DES versus Bare Early Generation DES versus Bare MetalMetal StentsStents

Mortality Repeat RevascStettler C et al. Lancet 2007;370:937‐48

Mortality Repeat Revasc

SES vs BMS 1 00 (0 82 1 25) SES vs BMS 0 30 (0 24 0 37)

HR (95% CI) HR (95% CI)

SES vs BMS

PES vs BMS

SES vs PES

1.00 (0.82‐1.25)

1.03 (0.84‐1.22)

0 96 (0 83 1 24)

SES vs BMS

PES vs BMS

SES vs PES

0.30 (0.24‐0.37)

0.42 (0.33‐0.53)

0 70 (0 56 0 84)

10∙2 2 50∙5

SES vs PES 0.96 (0.83‐1.24)

10∙2 2 50∙5

SES vs PES 0.70 (0.56‐0.84)

50

30

40

50NNT=35(CI 23-65)

10

20

30

NNT=7(CI 6 8)

NN

T

NNT=8(CI 7 10)

0

10

SES vs BMS PES vs BMS SES vs PES

(CI 6-8) (CI 7-10)

Progress Progress WithWith NewerNewer Generation DrugGeneration Drug‐‐ElutingEluting StentsStents

Newer Generation DES Efficacy and Safety

E liE li El tiEl ti Si liSi li El tiEl ti St tSt tEverolimusEverolimus--ElutingEluting versus versus SirolimusSirolimus--ElutingEluting StentsStents

Target Lesion Revasc Definite STTarget Lesion Revasc Definite ST

Favors EES Favors SES Favors EES Favors SES

Stefanini, WindeckerUpdated Meta-Analysis N = 11,167

BernBern‐‐Rotterdam Rotterdam CohortCohort Study Study Very Late Definite ST (1 4 yrs)

5EES vs SES HR* 0 33 95% CI 0 15 0 72

Very Late Definite ST (1-4 yrs)Räber et al. Circulation 2012; 125:1110-21

4

%)

EES vs. SES HR* = 0.33, 95% CI 0.15 – 0.72, P=0.006

EES vs. PES HR* = 0.24, 95% CI 0.13‐0.47, 

3

cide

nce

(% P <0.0001

Paclitaxel Stent 2 4%

2

ulat

ive

inc Paclitaxel Stent 2.4%

1

Cum

u

Sirolimus Stent 1.6%

0 Everolimus Stent 0.6%

0 6 12 18 24 30 36 42 48Months after index PCI

*from Cox proportional hazards model

StentStent ThrombosisThrombosis WithWith EverolimusEverolimus‐‐ElutingElutingStentsStents andand BareBare MetalMetal StentsStentsStentsStents andand Bare Bare MetalMetal StentsStents

A Network Meta-AnalysisPalmerini T et al Lancet 2012Palmerini T et al. Lancet 2012

Impact of PolymerImpact of Polymer‐‐Drug Coating and Platform Drug Coating and Platform Design on Early StentDesign on Early Stent ThrombogenicityThrombogenicityDesign on Early Stent Design on Early Stent ThrombogenicityThrombogenicity

Kolandaivelu K et al. Circulation 2011;123:1400-1409.

P=0.011 P=0.036

n81

umSten

t/MLV

ision

G Adsorba

nceS

LD

Pooled BMS: ML Vision, Driver, Taxus, Bx VelocityPooled DES: Xience V, Endeavor, Taxus Libertè, Cypher

Biodegradable Polymer Based DES Platforms

Sirolimus – ISAR TEST Biolimus A9 – BioMatrixNobori, Axxess, XTENT Sirolimus – ORSIRO

Sirolimus – Genous E erolim s SYNERGY No olim s DES ne BDBioengineered R Stent Everolimus – SYNERGY Novolimus – DESyne BD

LEADERS Trial – Primary EndpointCardiac death MI or Clinically indicated TVRCardiac death, MI, or Clinically-indicated TVR

Stefanini G et al. Lancet 2011;378:1940-8

25

BES SES

23.1%

3-year RR0.80 (0.63 - 1.01)

2-year RR0.83 (0.64 - 1.07)

4-year RR0.81 (0.66 - 1.00)

1-year RR0.88 (0.66 - 1.17)

15

20

19.1%15.5%

19.3%

Δ 3.7

Δ 4.0

10

15

% 13%15.6%12.1%

Δ 1.4

Δ 2.5

P < 0 00015

10.7%Pnon-inferiority < 0.0001

Psuperiority = 0.050

00 6 12 18 24 30 36 42 48

MonthsN b t i kNumbers at risk

SES 850 775 738 718 702 676 656 639 614

BES 857 781 749 733 723 710 697 677 659

BiodegradableBiodegradable Polymer DES versus Polymer DES versus Durable PolymerDurable Polymer SirolimusSirolimus ElutingEluting StentsStentsDurable Polymer Durable Polymer SirolimusSirolimus ElutingEluting StentsStents

Stefanini G et al. Lancet 2011

DESDES SafetySafety –– RiskRisk ofof StentStent ThrombosisThrombosis

Definite ST Definite ST

DES DES SafetySafety –– RiskRisk ofof StentStent ThrombosisThrombosis

BP‐DES DP‐SES RR (95% CI)

in available randomized studies in LEADERS trial through 4 years fup

1 to 4 year* RR 0.20 (95% CI 0.06‐0.67) 

p=0.004ISAR TEST 4

ISAR‐TEST 3

9/1299

1/202

9/652

2/202

0 50 (0 20 1 26)

0∙50 (0∙05, 5∙47) 0 to 1 year*RR 0.99 (95% CI 0.51‐1.95)

p=0.98  

LEADERS

ISAR‐TEST 4

20/857

9/1299

32/850

9/652

0∙62 (0∙36, 1∙08)

0∙50 (0∙20, 1∙26)

Overall (I‐squared = 0∙0%, p=0∙92) 0∙58 (0∙37, 0∙93)

10∙1 0∙2 2 50∙5

* RR 0‐1 vs RR 1‐4 p for interaction=0.017

Favoursbiodegradablepolymer DES

Favoursdurable 

polymer SES

Risk ratio

Biodegradable Polymer BES vs Durable Polymer SESAssociation of Cardiac Events With Definite ST

BES SES RR (95% CI) P P‐interNOT ASSOCIATED with ST

Association of Cardiac Events With Definite ST Stefanini G et al. Lancet 2011;378:1940-8

Cardiac death, MI, or TVR 0∙70≤1 year 78/857 87/850 0∙89 (0∙65‐1∙20) 0∙441 to 4 years 67/749 79/738 0∙81 (0∙59‐1∙12) 0∙21

Cardiac death or MI 0∙43

NOT ASSOCIATED with ST

Cardiac death or MI 0 43≤1 year 48/857 47/850 1∙02 (0∙68‐1∙53) 0∙941 to 4 years 43/779 52/781 0∙80 (0∙54‐1∙21) 0∙30

Clinically‐indicated TVR 0∙64≤1 year 37/857 45/850 0∙81 (0∙52‐1∙25) 0∙33≤1 year 37/857 45/850 0 81 (0 52 1 25) 0 331 to 4 years 39/776 40/760 0∙94 (0∙60‐1∙45) 0∙77

C di d th MI TVR 0 049

ASSOCIATED with STCardiac death, MI, or TVR 0∙049

≤1 year 13/857 15/850 0∙86 (0∙41‐1∙80) 0∙681 to 4 years 2/749 11/738 0∙17 (0∙04‐0∙78) 0∙009

Cardiac death or MI 0∙08≤1 year 11/857 11/850 1 00 (0 43 2 30) 0 99≤1 year 11/857 11/850 1∙00 (0∙43‐2∙30) 0∙991 to 4 years 3/779 11/781 0∙27 (0∙08‐0∙95) 0∙029

Clinically‐indicated TVR 0∙07≤1 year 13/857 15/850 0∙85 (0∙41‐1∙80) 0∙681 to 4 years 2/776 10/760 0∙19 (0∙04 0∙87) 0∙0171 to 4 years 2/776 10/760 0∙19 (0∙04‐0∙87) 0∙017

0∙1 0∙2 0∙5 1 2 4 6

Favours BES Favours SES

≤1 year

1 to 4 years

SYNERGY™ StentMeredith I et al. J Am Coll Card 2012

Bioabsorbable polymer (PLGA)(PLGA)

Applied only to the abluminal surface ( ll t)(rollcoat)

Thin strut PtCr Stent

Designed for polymer resorption within 4 months

PLGA BioabsorbablePolymer

Designed for polymer resorption within 4 months

+Everolimus

on Abluminal Side of Stentof Stent 

Randomized Evaluation of a Novel Biodegradable Polymer‐Based Everolimus‐Eluting Coronary Stent

1°EP: In-Stent Late Loss

Polymer‐Based Everolimus‐Eluting Coronary StentMeredith I et al. J Am Coll Card 2012

Target Lesion Failure1 EP: In Stent Late Loss @ 6 Months

P=0 19

Target Lesion Failure @ 6 Months

0.5

0.6P=0.19

P=0.568

10 P=1.00

P=0.72

0 3

0.4

ss, m

m

4 1

6

ents

, %0.2

0.3

Late

lo

3.12.2

4.1

2

4Patie

0.15 0.10 0.130.0

0.1

SYNERGYPROMUS SYNERGY 0

2

PROMUS SYNERGY SYNERGY½ DoseElement™ PE SYN SYN ½Element ½ Dose

(N=98) (N=94) (N=99) (N=98) (N=94) (N=99)

6‐month versus 24‐month DAPT after PCIValgimigli M et al Circulation 2012

1°EP D h MI CVA T II III V BARC Bl di

Valgimigli M et al. Circulation 2012

1°EP: Death, MI, or CVA@ 2 Years

Type II, III, or V BARC Bleeding@ 2 Years

% %

12

14

12

14P=0.91

% %P=0.00018

10 10.1

8

10

7.48

10 HR 0.46 (95% CI 0.10-0.69)

4

6

3 54

6

2

4 3.5

2

4

0

6-month DAPT 24-month DAPT0

6-month DAPT 24-month DAPT

Impact of DAPT Discontinuation on Definite or Probable Stent Thrombosis with Everolimus‐ and

Kedhi E presented at ACC 2012

Probable Stent Thrombosis with Everolimus and Paclitaxel‐Eluting Stents Through 2 Years

Kedhi E. presented at ACC 2012

A Pooled Analysis of SPIRIT II, III, IV, and COMPARE Trials

6.2%6%

8%

EESPES

p for trend = 0.75p for trend = 0 05

4%

6% PES p for trend = 0.05

2.3% 2.3%

1 5%2%

4%

1.1%0.5% 0.5%

0.8%1.5%

0%

2%

Time of DAPT Discontinuation

1 to 6months

6 to 12months

12 to 24months

NOdiscontinuation

PolymerPolymer‐‐Free DES Free DES PlatformsPlatformsYUKON BioFreedom CRE8

DFS Technology Amazon PaxDFS Technology Amazon Pax

Polymer‐Free Biolimus‐A9 Coated StentTada N et al. Circ Cardiovasc Interv 2010;3:174‐83

90%

100%

Biolimus A9 Elution from Stents

(MEDIUM: PBS pH 7.4/Tween, 37°C)

Biolimus A9

20%

30%

40%

50%

60%

70%

80%

Cum

ulat

ive

Rel

ease

(%)

Bi

Struts With Fibrin Inflammation Score Struts With Giant Cells

0%

10%

0 5 10 15 20 25 30 35 40 45 50Time (Hrs)

78

961000.86

0 8

18.7

8

10

Struts With Fibrin Inflammation Score Struts With Giant Cells

51

78

60

80

% %0.6

0.8

6

8

20

40% %

0.28 0.31

0.2

0.42.9 2.6

2

4

0

BMS BioFreedom SES

0

BMS BioFreedom SES

0

BMS BioFreedom SES

Polymer Free AmphilimusPolymer Free Amphilimus‐‐Eluting Cre8™ StentEluting Cre8™ StentCRE8 Release KineticPolymer Free Abluminal Reservoir Technology

Bio Inducer Surface(i‐Carbofilm)

Amphilimus Formulation(Sirolimus + Organic Acid)(i‐Carbofilm) (Sirolimus + Organic Acid)

Pre Clinical In-Vivo AAssessment

Moretti et al. EuroIntervention 2011

Cre8™ Stent versus Cre8™ Stent versus PaclitaxelPaclitaxel‐‐Eluting StentEluting StentCarrié D et al. J Am Coll Cardiol 2012

Cardiac Death, MI, or TLR @ 12 Months

1°EP: In-stent Late Loss@ 6 Months

8%

P=0 81

Diabetic SubgroupOverall

0 4

0.5P<0.0001mm

0 4

0.5

0.43±0.41

P=0.0002

6.16.8

6

P=0.81

0.3

0.4

0.3

0.4

0.34±0.40

4

6

0 1

0.20.2

0.14±0.36 0 12±0 29 2

4

0

0.1

0

0.10.12±0.29

0

2

Cre8 TAXUS Libertè

(N=141) (N=135)

0

Cre8 TAXUS Libertè

(N=42) (N=33)

0Cre8 TAXUS Libertè

(N=148) (N=148)

Biodegradable Vascular Scaffolds (BVS)

1996

Van der Giessen Circulation

TamaiCirculation

OrmistonLancet

ErbelLancet

2000 2007 2008

JabaraPCR 2009

2009

AbizaidTCT 2009

HaudePCR 2011

20111996

AMS-1

2000 2007 2008 2009

IDEAL BDS DREAMS

2011

Animal studiespolymeric scaffoldsrevealing excessive

AMS-1first bioabsorbablemetallic non drug-

eluting scaffoldN=64

Polyanhidrideester and salicylic acid,

drug-eluting scaffoldN=11

DREAMSfirst drug-eluting

bioabsorbablemetallic scaffold

N=22ginflammatory reactions

Igaki TamaiFirst fully

Bioresorbable vascular scaffold

N=64

REVAPolycarbonate stent,

radiopaque non drug-

N 22

First fully biodegradable non

drug eluting scaffold N=15

vascular scaffoldfirst bioabsorbable drug

eluting scaffoldN=31

radiopaque, non drug-eluting scaffold

N=31

Fully Fully BioabsorbableBioabsorbable EverolimusEverolimus‐‐Eluting StentEluting StentO i t J t l L t 2008 371 899 907Ormiston J et al. Lancet 2008;371:899-907

Everolimus/PLLA MatrixMatrix Thin coating layer-1:1 ratio of Everolimus/PDLLA-Controlled drug releasereleasePLLA stent backbone-stent integrity-semicrystallinepolymer

Device success: 94% MACE(TLR):3.3% ST: 0% @ 12 months

Late loss (in-stent): 0.44±0.35 mm

Cumulative Cumulative Late Lumen Loss Among ABSORB Late Lumen Loss Among ABSORB Cohort B Cohort B 

Serruys PW. Presented at TCT 2011

and and Patients Treated With Patients Treated With EverolimusEverolimus‐‐Eluting StentsEluting Stents

ABSORB Vasomotor Function Testing Through 2 Years

1 6 Months1 12 Months2 24 Months3

)

1

(N=15)

6 Months1

(N=6) (N=19)

12 Months2

(N=13) (N=9)

24 Months3

(N=7)

ion

Cohort B1 Cohort B2 Cohort A

n)

eter

(mm

)

0.5

Vaso

dila

ti

-dru

g in

fusi

on

sel D

iam

e

0

ctio

n

usio

n to

pos

t-

Δin

Ves

-0.5

Vaso

cons

tric

(pre

-dru

g in

fu

MethergineAcetylcholine

-1

V

2. Adapted from Serruys, PW. ACC 20111. Adapted from Serruys, PW. ACC 2011

3. Adapted from Serruys, PW, et al. Lancet 2009; 373: 897-910.

BIOSOLVEBIOSOLVE‐‐I IVUS Results at 6I IVUS Results at 6‐‐month month Waksman R presented at CRT 2012

Post implantation 6-month Follow-upScaffoldDegradation

Waksman R. presented at CRT 2012

Contribution to lumen loss

Loss of scaffolding area

In-stentneointima

53% 47%

0.38 mm 0.26 mm0.64 mm LLL

0.57 mm 0.51 mm1.08 mm LLL

47%

PROGRESS**

BIOSOLVE-I 0.64 mm LLL

33% less 49% less41% less

BIOSOLVE I

* N= 12 evaluable IVUS runs (volumetric) available at 6-month follow-up for cohort 1**Erbel R. et al., Lancet 2007;369:1869-75,

Waksman et.al, JACC Cardiovasc Intervent 2009;2:312-320

Newer Generation Drug‐Elutingg gStents…What Have We Achieved?

Improved safety• Reduced risk of stent thrombosis• Reduced risk of cardiac death or MI associated with ST

Improved efficacyR d d i k f TLR• Reduced risk of TLR

Decreased need for DAPTDecreased need for DAPT• Near elimination stent thrombosis associated with DAPT

discontinuation

Questions for TomorrowQuestions for Tomorrow

• Is a very short (<6 months) DAPT safe?• Are newer generation DES safer than BMS?Are newer generation DES safer than BMS?• Are biodegradable polymer based DES

superior to newer generation durable polymersuperior to newer generation durable polymer based DES?

• Are polymer-free DES able to achieve equivalent clinical efficacy as polymer based DES?

• Will BVS outperform newer generation DES?p g