M. Valgimigli University of Ferrara Italy ESC Congress 2007 Three-year clinical follow-up after sirolimus-eluting versus bare metal stent implantation assisted by systematic GP IIb/IIIa infusion in patients with MI Thank you very much mr chairmen and I also would like to thank the organizers foir this kind invitation When this title was proposed to me some months ago already, I accepted it without asking for any changes. Indeed I think today that was a major mistake by my side since surprisingly we do not have any consensus regarding the definition of elective versus non elective percutaneous coronary intervention and the only way we have to adopt a clear definition in this setting is to look at surgical iterature: the Euro score is a tool employed to risk stratify the patients befroe cardiac surgery and it defines... But still, even with this in mind it is difficult to understand the clinical implications of this definition in our PCI-based practice, that’s why I would like to discuss with you in the next couple of slides two real clinical scenarios that required PCI in our institution in the last month. Before discussing wi th you current evidence regarding the role of IIB 3° inhibitors in the PCI setting, I would like ot psend the next couple of slides in trying to define he elective intervention, Surprisinglt despite almost universal use of the term, the re is no conseus in the distinction between elective vs non elective procedure as far the percutaneous coronary interventino is concerned. Therefore, to make clear what we are speaking about we are forced to adopt a surgical definition The euro score is tool and despite th ename it is really worldwide accepted. M. Valgimigli University of Ferrara Italy MI = myocardial infarction Vienna 2nd September 07

Study Design Inclusion criteria: STEMI all comers: shock, elderly included Exclusion criteria: Contraindications to GP IIb/IIIa Tirofiban SHDB Cypher STEMI UFH - ASA Clopidogrel BMS Abciximab standard regimen CCU Cath-Lab ASA = acetylsalicylic acid, BMS = bare metal stent, GP = glycoprotein, STEMI = ST-segment elevation myocardial infarction, UFH = unfractioned heparin. Valgimigli M et al. Cardiovasc Drugs Ther 04; 18: 225-30.

“should be currently regarded as the gold standard for STEMI” BMS and abciximab display a synergistic role in primary PCI setting and… “should be currently regarded as the gold standard for STEMI” Abciximab Tirofiban B M S D E S BMS = bare metal stent, DES = drug-eluting stent, PCI = percutaneous coronary intervention, STEMI = ST-segment elevation myocardial infarction. Medical Costs

Study Profile SHDB Tirofiban Abciximab 85% 88% 75% 77% 219 Assessed for Eligibility 44 Excluded 34 Not Meeting Inclusion Criteria 10 Refused to Participate 175 Randomized 1:1 SHDB Tirofiban (n = 87) Abciximab (n = 88) 3 POBA 74 SES 7 BMS 84 PTCA 85% 88% 3 No PCI 83 PTCA 5 No PCI 4 POBA 77 BMS 2 SES 75% 77% 3 3 74 7 Clinical Follow-up Angiographic Follow-up Pts not eligible Refused to participate 4 77 2 5 1 62 4 1 64 1 3 2 6 3 4 5 6 3 9 1 BMS = bare metal stent, PCI = percutaneous coronary intervention, POBA = plain old balloon angioplasty, PTCA = percutaneous transluminal coronary angioplasty, SES = sirolimus-eluting stent, SHDB = single high dose bolus. Valgimigli M et al. JAMA 2005; 293: 2109-17.

30-Day Outcome (n = 175) % p > 0.99 p = 0.62 p = 0.62 p > 0.99 Abciximab+BMS Tirofiban+SES *in 1 pt SES was implanted as protocol violation % p > 0.99 p = 0.62 p = 0.62 p > 0.99 AMI = acute myocardial infarction, BMS = bare metal stent, SES = sirolimus-eluting stent, ST = sinus tachycardia, TVR = target vessel revascularization. Valgimigli M et al. JAMA 2005; 293: 2109-17.

8-Month Outcome (n = 175) 41% % 15% Death MI CVA BR 1° Endpoint* Abciximab+BMS p = 0.004 Tirofiban+SES * In all recruited pts % 15% p = 0.8 p = 0.6 p > 0.99 Death MI CVA BR 1° Endpoint* BMS = bare metal stent, BR = binary restenosis, SES = sirolimus-eluting stent, ST = sinus tachycardia, TVR = target vessel revascularization. Valgimigli M et al. JAMA 2005; 293: 2109-17.

Death/MI/TVR at 8 Months p=0.043 HR 0.53 [95% CI: 0.28-0.92] Valgimigli M et al. JAMA 2005; 293: 2109-17.

Duration of Dual Antiplatelet Tx 5 pts (4 tirofiban+SES) re-started clopidogrel beyond the 2 year follow-up BMS = bare metal stent, SES = sirolimus-eluting stent, Tx = treatment.

Primary EP at 3 years * P=0.008 % 49% 29% No lost to Follow-up 70 Abciximab+BMS Tirofiban+SES 60 P=0.008 50 % 49% 40 30 29% 20 1° EP: composite of death, MI, CVA and binary restenosis *: in all recruited patients

All Cause Mortality at 3 Years 16% 15% BMS = bare metal stent, SES = sirolimus-eluting stent.

Death/MI at 3 Years 23% 20% P=0.57 at log rank test BMS = bare metal stent, SES = sirolimus-eluting stent.

TVR at 3 Years 25% 10% BMS = bare metal stent, SES = sirolimus-eluting stent, TVR = target vessel revascularization

MACE Rate at 3 Years 41% 29% BMS = bare metal stent, CI = confidence interval, SES = sirolimus-eluting stent, TVR = target vessel revascularization.

Stent Thrombosis at 3 Years 6.8% 5.7% BMS = bare metal stent, SES = sirolimus-eluting stent.

Conclusions At 3 year Follow-up the composite of death MI CVA and BR was lower in tirofiban+SES arm This difference was driven by an improvement in angiographic outcome leading to lower TVR There was no difference in terms of death, MI or cumulative probability of stent thrombosis according to ARC classification Long-term results of larger RCT are awaited to confirm our encouraging but still preliminary findings