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 problem  Second generation drug-eluting stents  Update on endothelial progenitor cell capturing stents

25% Stent Thrombosis !

 Scope of the problem  Second generation drug-eluting stents  Update on endothelial progenitor cell capturing stents

 Scope of the problem  Second generation drug-eluting stents  Update on endothelial progenitor cell capturing stents

accelerated endothelialization by EPC-“capturing” immediately after Stent Implantation Endothelialization of the Stent Struts:

GenousBMS (%) p=0.07 mean In rabbit iliac model BMSGenous 7-days Anti-CD34 coating

Confocal SES-anti-CD34 SES alone 3 days 14 days

LATIN AMERICA Venezuela 1 MIDDLE EAST Egypt 6 Lebanon 1 Saudi Arabia 1 Syria 3 Turkey 3 EUROPE Austria 8 Belgium 3 Cyprus 2 Denmark 2 France 8 Germany 11 Greece 6 Ireland 1 Italy 26 Netherlands 5 Portugal 3 Spain 8 Switzerland 1 United Kingdom 9 NORTH AFRICA Tunisia 2 ASIA PACIFIC Australia 6 Hong Kong 1 Malaysia 9 Singapore SITES Czech Republic 5 Finland 1 Hungary 2 Poland 2 Romania 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 days6 months12 months Cardiac Death0.6 %1.3 %1.9 % MI1.2 %1.5 %1.6 % Q-wave0.2 % Non Q-wave1.0 %1.3 %1.4 % TLR (Clinically Driven)0.2 %2.9 %5.0 % PCI0.2 %2.6 %4.6 % CABG0.0 %0.3 %0.4 % MACE1.9 %5.8 %8.5 % Acute stent thrombosis0.2 % Sub-acute stent thrombosis0.4 % Late stent thrombosis0.3 %

Acute stent thrombosis0.0 % Sub-acute stent thrombosis0.2 % Late stent thrombosis0.8 % 30 days6 months12 months Cardiac Death0.8 %2.5 %3.6 % MI0.6 %1.3 % Q-wave0.1 % Non Q-wave0.5 %1.2 % TLR (Clinically Driven)0.2 %3.2 %4.9 % PCI0.2 %2.8 %4.5 % CABG0.0 %0.4 %0.5 % MACE1.6 %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 thrombosis0.2 % Sub-acute stent thrombosis0.3 % Late stent thrombosis0.4 % 30 days6 months12 months Cardiac Death0.6 %1.2 %1.7 % MI1.1 %1.3 %1.4 % Q-wave0.1 % 0.2 % Non Q-wave0.9 %1.2 % TLR (Clinically Driven)0.2 %3.0 %5.2 % PCI0.2 %2.6 %4.7 % CABG0.0 %0.4 %0.5 % MACE1.8 %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 thrombosis0.4 % Sub-acute stent thrombosis0.7 % Late stent thrombosis0.2 % 30 days6 months12 months Cardiac Death0.5 %2.2 %3.3 % MI1.6 %2.7 %2.5 % Q-wave0.4 %0.5 % Non Q-wave1.3 %2.2 %2.0 % TLR (Clinically Driven)0.4 %2.5 %4.2 % PCI0.4 %2.5 %4.2 % CABG0.0 % MACE2.5 %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 criteriaall comers 3-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 TLR 2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept ARC definite + probable

Genous (e-HEALING) Cypher (LEADERS) BioMatrix (LEADERS) Taxus (SYNTAX) Inclusion criteriaall comers 3-VD / Left main Number of patients Duration of follow-up12 months9 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 TLR 2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept ARC definite + probable

Genous (e-HEALING) Cypher (LEADERS) BioMatrix (LEADERS) Taxus (SYNTAX) Inclusion criteriaall comers 3-VD / Left main Number of patients Duration of follow-up12 months9 months 12 months Cardiac death1.9 % %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 TLR 2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept ARC definite + probable

Genous (e-HEALING) Cypher (LEADERS) BioMatrix (LEADERS) Taxus (SYNTAX) Inclusion criteriaall comers 3-VD / Left main Number of patients Duration of follow-up12 months9 months 12 months Cardiac death1.9 % %1.6 % 4.3 % (any) MI1.6 % %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 TLR 2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept ARC definite + probable

Genous (e-HEALING) Cypher (LEADERS) BioMatrix (LEADERS) Taxus (SYNTAX) Inclusion criteriaall comers 3-VD / Left main Number of patients Duration of follow-up12 months9 months 12 months Cardiac death1.9 % %1.6 % 4.3 % (any) MI1.6 % %5.7 % 4.8 % TLR Clinically Driven5.0 % %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 TLR 2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept ARC definite + probable

Genous (e-HEALING) Cypher (LEADERS) BioMatrix (LEADERS) Taxus (SYNTAX) Inclusion criteriaall comers 3-VD / Left main Number of patients Duration of follow-up12 months9 months 12 months Cardiac death1.9 % %1.6 % 4.3 % (any) MI1.6 % %5.7 % 4.8 % TLR Clinically Driven5.0 % %4.3 % 13.7 % MACE8.5 % % % % 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 TLR 2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept 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 TLR 2 MACE = Cardiac Death, MI TVR; The Lancet, 372: 1163 – 1173, MACE = any death, MI, TVR, Syntax Trial, presented at the ESC meeting in Munich, Sept ARC definite + probable Genous (e-HEALING) Cypher (LEADERS) BioMatrix (LEADERS) Taxus (SYNTAX) Inclusion criteriaall comers 3-VD / Left main Number of patients Duration of follow-up12 months9 months 12 months Cardiac death1.9 % %1.6 % 4.3 % (any) MI1.6 % %5.7 % 4.8 % TLR Clinically Driven 5.0 % %4.3 % 13.7 % MACE8.5 % % % % 3 Stent thrombosis1.0 % % % % 4 Recommended dual antiplatelet therapy4 weeks12 months

 Study flow chart 2007: 400 P-PCI 100 patients included 100 patients included (Randomization ) 50 Genous TM 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 outcome MACE CV Deaths MI TLR ST P=0.03 P=NS P=0.04 P=NS (Non hierachical) Genous TM CrCo

 6 month angio and IVUS data Genous Cr-Co P value Genous Cr-Co P value ANGIO DATA N=44 N=47 Late lumen loss (mm) 0.89± ±0.47 NS Late lumen loss (mm) 0.89± ±0.47 NS Restenosis (>50%) NS Restenosis (>50%) NS (QCA: Pie Medical Im) (QCA: Pie Medical Im) IVUS N=41 N=42 mean in-stent NIH (mm 3 ) 49.7 ± ±22.8 NS mean in-stent NIH (mm 3 ) 49.7 ± ±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 Genous TM group P-PCI Day 30 Day 60 ASA ASA+clopidogrel ARC definition: ARC definition: 3x definite; 3x late Patient Age TIMI Thrombus iGP IIb/IIa Vessel EF Stent Days Treatment Dual T Stát. J.J Y Y RCA 60 1; 2.75/23 48 dPOBA N Alive P.U Y Y LAD 45 1; 3/23 32 dPCI+G Y Alive J.T Y Y RCA 52 2; 3.5/ dPOBA N Alive J.T Y Y RCA 52 2; 3.5/ 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  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 Diabetes3234 Smoke Dislipidemia 4663 Familyhistory Pre PTCA Pre CABG p NS Pre EF45 NS Genous DES Hypertension NS (n=100) (n=95) Male ± ± (%)

CX (%) PTCA Multivessel (%) RCA (%) LAD (%) p NS 3 73 NS 22.67±9 Lesion length (mm) Genous DES 26.9± Multiple stenting (%) NS IIb/IIIa (%) TIMI grade post 62 Direct stenting (%)

Genous DES % p=0.045 p=0.013 p=0.017 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