giuseppe biondi zoccai, md, fsici-gise university of turin, turin, italy

Giuseppe Biondi Zoccai, MD, FSICI-GISE

University of Turin, Turin, Italy

Scope of the problem

Second generation drug-eluting stents

Update on endothelial progenitor cell capturing stents

Scope of the problemScope of the problem

Second generation drug-eluting stents

Update on endothelial progenitor cell capturing stents

25% Stent Thrombosis !

Scope of the problem

Second generation drug-eluting Second generation drug-eluting stentsstents

Update on endothelial progenitor cell capturing stents

Scope of the problem

Second generation drug-eluting stents

Update on endothelial Update on endothelial progenitor cell capturing stentsprogenitor cell capturing stents

accelerated endothelializationby EPC-“capturing”

immediately after Stent Implantation

Endothelialization of the Stent Struts:

0

10

20

30

40

50

Genous BMS

(%)

p=0.07

mean

mean

In rabbit iliac model

BMSGenous7-days

Anti-CD34 coating

Confocal

SES-anti-CD34 SES alone

3 days

14 days

LATIN AMERICAVenezuela 1

MIDDLE EASTEgypt 6Lebanon 1Saudi Arabia 1Syria 3Turkey 3

EUROPEAustria 8Belgium 3Cyprus 2Denmark 2France 8Germany 11Greece 6Ireland 1Italy 26Netherlands 5Portugal 3Spain 8Switzerland 1United Kingdom 9

NORTH AFRICATunisia 2

ASIA PACIFICAustralia 6Hong Kong 1Malaysia 9Singapore 2

144 SITES

Czech Republic 5 Finland 1Hungary 2Poland 2Romania 1 Russian Federation 5

Patients treated on or before Feb 22, 2007 All events reported before Aug 12, 2008; all events adjudicated by CEC Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR

30 days 6 months 12 months

Cardiac Death 0.6 % 1.3 % 1.9 %

MI 1.2 % 1.5 % 1.6 %

Q-wave 0.2 % 0.2 % 0.2 %

Non Q-wave 1.0 % 1.3 % 1.4 %

TLR (Clinically Driven) 0.2 % 2.9 % 5.0 %

PCI 0.2 % 2.6 % 4.6 %

CABG 0.0 % 0.3 % 0.4 %

MACE 1.9 % 5.8 % 8.5 %Acute stent thrombosis 0.2 %

Sub-acute stent thrombosis 0.4 %

Late stent thrombosis 0.3 %

Acute stent thrombosis 0.0 %

Sub-acute stent thrombosis 0.2 %

Late stent thrombosis 0.8 %

30 days 6 months 12 months

Cardiac Death 0.8 % 2.5 % 3.6 %

MI 0.6 % 1.3 % 1.3 %

Q-wave 0.1 % 0.1 % 0.1 %

Non Q-wave 0.5 % 1.2 % 1.2 %

TLR (Clinically Driven) 0.2 % 3.2 % 4.9 %

PCI 0.2 % 2.8 % 4.5 %

CABG 0.0 % 0.4 % 0.5 %

MACE 1.6 % 6.9 % 9.9 %

Patients treated on or before Feb 22, 2007 All events reported before Aug 12, 2008; all events adjudicated by CEC Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR

Acute stent thrombosis 0.2 %

Sub-acute stent thrombosis 0.3 %

Late stent thrombosis 0.4 %

30 days 6 months 12 months

Cardiac Death 0.6 % 1.2 % 1.7 %

MI 1.1 % 1.3 % 1.4 %

Q-wave 0.1 % 0.1 % 0.2 %

Non Q-wave 0.9 % 1.2 % 1.2 %

TLR (Clinically Driven) 0.2 % 3.0 % 5.2 %

PCI 0.2 % 2.6 % 4.7 %

CABG 0.0 % 0.4 % 0.5 %

MACE 1.8 % 5.5 % 8.2 %

Patients treated on or before Feb 22, 2007 All events reported before Aug 12, 2008; all events adjudicated by CEC Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR

Acute stent thrombosis 0.4 %

Sub-acute stent thrombosis 0.7 %

Late stent thrombosis 0.2 %

30 days 6 months 12 months

Cardiac Death 0.5 % 2.2 % 3.3 %

MI 1.6 % 2.7 % 2.5 %

Q-wave 0.4 % 0.5 % 0.5 %

Non Q-wave 1.3 % 2.2 % 2.0 %

TLR (Clinically Driven) 0.4 % 2.5 % 4.2 %

PCI 0.4 % 2.5 % 4.2 %

CABG 0.0 % 0.0 % 0.0 %

MACE 2.5 % 7.4 % 9.9 %

Patients treated on or before Feb 22, 2007 All events reported before Aug 12, 2008; all events adjudicated by CEC Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR

Genous(e-HEALING)

Cypher(LEADERS)

BioMatrix(LEADERS)

Taxus(SYNTAX)

Inclusion criteria all comers all comers all comers3-VD / Left

main

1 All events reported before Aug 12, 2008; all events adjudicated by CEC; Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, 20083 MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept. 20084 ARC definite + probable

Genous(e-HEALING)

Cypher(LEADERS)

BioMatrix(LEADERS)

Taxus(SYNTAX)

Inclusion criteria all comers all comers all comers3-VD / Left

main

Number of patients 3196 850 857 903

Duration of follow-up 12 months 9 months 9 months 12 months

1 All events reported before Aug 12, 2008; all events adjudicated by CEC; Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, 20083 MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept. 20084 ARC definite + probable

Genous(e-HEALING)

Cypher(LEADERS)

BioMatrix(LEADERS)

Taxus(SYNTAX)

Inclusion criteria all comers all comers all comers3-VD / Left

main

Number of patients 3196 850 857 903

Duration of follow-up 12 months 9 months 9 months 12 months

Cardiac death 1.9 % 1 2.5 % 1.6 % 4.3 % (any)

1 All events reported before Aug 12, 2008; all events adjudicated by CEC; Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, 20083 MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept. 20084 ARC definite + probable

Genous(e-HEALING)

Cypher(LEADERS)

BioMatrix(LEADERS)

Taxus(SYNTAX)

Inclusion criteria all comers all comers all comers3-VD / Left

main

Number of patients 3196 850 857 903

Duration of follow-up 12 months 9 months 9 months 12 months

Cardiac death 1.9 % 1 2.5 % 1.6 % 4.3 % (any)

MI 1.6 % 1 4.6 % 5.7 % 4.8 %

1 All events reported before Aug 12, 2008; all events adjudicated by CEC; Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, 20083 MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept. 20084 ARC definite + probable

Genous(e-HEALING)

Cypher(LEADERS)

BioMatrix(LEADERS)

Taxus(SYNTAX)

Inclusion criteria all comers all comers all comers3-VD / Left

main

Number of patients 3196 850 857 903

Duration of follow-up 12 months 9 months 9 months 12 months

Cardiac death 1.9 % 1 2.5 % 1.6 % 4.3 % (any)

MI 1.6 % 1 4.6 % 5.7 % 4.8 %

TLR Clinically Driven 5.0 % 1 4.9 % 4.3 % 13.7 %1 All events reported before Aug 12, 2008; all events adjudicated by CEC; Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, 20083 MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept. 20084 ARC definite + probable

Genous(e-HEALING)

Cypher(LEADERS)

BioMatrix(LEADERS)

Taxus(SYNTAX)

Inclusion criteria all comers all comers all comers3-VD / Left

main

Number of patients 3196 850 857 903

Duration of follow-up 12 months 9 months 9 months 12 months

Cardiac death 1.9 % 1 2.5 % 1.6 % 4.3 % (any)

MI 1.6 % 1 4.6 % 5.7 % 4.8 %

TLR Clinically Driven 5.0 % 1 4.9 % 4.3 % 13.7 %

MACE 8.5 % 1 10.5 % 2 9.2 % 2 17.2 % 3

1 All events reported before Aug 12, 2008; all events adjudicated by CEC; Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, 20083 MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept. 20084 ARC definite + probable

1 All events reported before Aug 12, 2008; all events adjudicated by CEC; Worst MACE per patient = cardiac death, MI, CABG, and clinically driven TLR2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, 20083 MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept. 20084 ARC definite + probable

Genous(e-HEALING)

Cypher(LEADERS)

BioMatrix(LEADERS)

Taxus(SYNTAX)

Inclusion criteria all comers all comers all comers3-VD / Left

main

Number of patients 3196 850 857 903

Duration of follow-up 12 months 9 months 9 months 12 months

Cardiac death 1.9 % 1 2.5 % 1.6 % 4.3 % (any)

MI 1.6 % 1 4.6 % 5.7 % 4.8 %

TLR Clinically Driven 5.0 % 1 4.9 % 4.3 % 13.7 %

MACE 8.5 % 1 10.5 % 2 9.2 % 2 17.2 % 3

Stent thrombosis 1.0 % 4 2.2 % 4 2.7 % 4 3.4 % 4

Recommended dual antiplatelet therapy 4 weeks 12 months 12 months 12 months

Study flow chartStudy flow chart

2007:2007: 400 P-PCI400 P-PCI

100 patients included100 patients included

(Randomization)

50 GenousTM 50 CrCo

6-month clinical, angio and IVUS FU

ASA 100mg/day+clopidogrel 75mg/day 30 days; GPIIb/IIIa inhibitors

and thromboaspiration at the discretion of the physician

6-month clinical outcome6-month clinical outcome

0

5

10

15

20

25

30

MACE CV Deaths MI TLR ST

P=0.03

P=NS

P=0.04

P=NSP=NS

(Non hierachical)

GenousTM CrCo

24

10

4 4 6 2

14

4 6 0

4 4

2 2

6 month angio and IVUS data6 month angio and IVUS data

Genous Genous Cr-Co Cr-Co P valueP value

ANGIO DATAANGIO DATA N=44N=44 N=47 N=47 Late lumen loss (mm) 0.89±0.59 0.79±0.47 NSLate lumen loss (mm) 0.89±0.59 0.79±0.47 NS Restenosis (>50%) 20 13 NSRestenosis (>50%) 20 13 NS (QCA: Pie Medical Im)(QCA: Pie Medical Im)

IVUS N=41 N=42 mean in-stent NIH mean in-stent NIH (mm(mm33) ) 49.749.7±±4848 40.0±22.8 NS 40.0±22.8 NS (Volcano, pull back 0.5%mm/s)(Volcano, pull back 0.5%mm/s)

(QIVA Pie Medical Im)(QIVA Pie Medical Im)

Stent thrombosis in GenousStent thrombosis in GenousTMTM group group

P-PCI Day 30 Day 60

ASA

ASA+clopidogrel

32 48 52

ARC definition: ARC definition: 3x definite; 3x late

Patient Age TIMI Thrombus iGP IIb/IIa Vessel EF Stent Days Treatment Dual T Stát.Patient Age TIMI Thrombus iGP IIb/IIa Vessel EF Stent Days Treatment Dual T Stát.

J.J. 61 3 Y Y RCA 60 1; 2.75/23 48 dPOBA N AliveJ.J. 61 3 Y Y RCA 60 1; 2.75/23 48 dPOBA N Alive

P.U. 26 3 Y Y LAD 45 1; 3/23 32 dPCI+G Y AliveP.U. 26 3 Y Y LAD 45 1; 3/23 32 dPCI+G Y Alive

J.T. 47 2 Y Y RCA 52 2; 3.5/23+18 52 dPOBA N AliveJ.T. 47 2 Y Y RCA 52 2; 3.5/23+18 52 dPOBA N Alive

Single center trial – (Università degli Studi di Napoli - Federico II)

PI: F. Piscione 195 consecutive patients underwent PCI with

either Genous or DES (SES or PES) implantations in the period May – July 2006.

Dual anti-platelet therapy for 1 month post-Genous implant and 9 months post DES implant.

Clinical follow-up (average FU 10.1 ± 3.2 months).

Follow-up major adverse clinical events (MACE): cardiac death, MI, target vessel re-PTCA, CABG.

Age

Diabetes 32 34

Smoke 32.7 50

Dislipidemia 46 63

Familyhistory

38.2 33.4

Pre PTCA

Pre CABG

10.9

9.1

15.4

3.8

p

0.047

NS

NS

NS

NS

NS

NS

Pre EF 45 NS

Genous DES

Hypertension 70 80.6 NS

(n=100) (n=95)

Male 0.048

65.56±10.8

60.11±10.8 84 67.7

51

(%) (%)

CX (%) 16.3 26.2

PTCA Multivessel (%)

24.5 26.2RCA (%)

LAD (%) 57 43

p

NS

NS

NS

NS

3

73

NS

NS

22.67±9 Lesion length (mm)

3

57 44.6

Genous DES

26.9±12 0.049

Multiple stenting (%) 98.5 95.4

NS

IIb/IIIa (%)

TIMI grade post

62

Direct stenting (%) 43.8 72.3 0.002

1 1 2 24

7,8

11,8

7,85,8

22

0

10

20

30

MI Re-PCI Death Stentthrombosis

MACE

GenousDES

% p=0.045

p=0.013

p=0.017

p=NS p=NS

Coronary stents have always faced a significant risk of early and late stent thrombosis

Whereas second-generation drug-eluting stents have improved early and subsequent outcomes, their biocompatibility is still at stake

Recent studies on EPC stents suggest the promising role of this device

The asymptotic coronary stent will likely be a bioabsorbable device with drug-elution and EPC capabilities