AVIO: A Prospective, Randomized Trial of Intravascular-Ultrasound Guided Compared to Angiography Guided Stent Implantati

1. Late Breaking Trial/First Report Investigation Washington DC, September 25th 2010 • AVIO: A Prospective, Randomized Trial of Intravascular-Ultrasound Guided Compared to Angiography Guided Stent Implantation in Complex Coronary Lesions 12:15pm-12:25pm Antonio Colombo, MD San Raffaele Hospital Milan, Italy On behalf of the AVIO Investigators

2. Presenter Disclosure Information Antonio Colombo, MD Co-founder & minor shareholder: Cappella Inc.

3. AVIO trialAngiography Vs IVUS Optimization PRINCIPAL INVESTIGATORS/ PARTICIPATING CENTERS/ NUMBER (N) OF PATIENTS ENROLLED PER CENTER Antonio Colombo San Raffaele, Milan Italy N=50 Christophe CaussinHopital Marie Lannelongue, France N=42 Patrizia PresbiteroIstituto Clinico Humanitas, Milan, Italy N=24 Stefano Galli, Centro Cardiologico Monzino N=23 Alberto MenozziAzienda Ospedaliera Universitaria, Parma, Italy N=21 Ferdinando VarbellaOspedale degli Infermi, Rivoli, Italy N=17 Fina MauriGermans Trias i Pujol, Badalona, Spain N=15 Marco ValgimigliAzienda Ospedaliera Universitaria Ferrara, Italy N=15 Chourmouzios ArampatzisInterbalkan Medical Center, Thessaloniki, Greece N=13 Manuel SabateHospital Santa Creu i Sant Pau, Barcelona, Spain N=12 Andrejs ErglisP. Stradins Clinical University Hospital, Riga, Latvia N=11 Bernhard ReimersOspedale Civile, Mirano, Italy N=11 Flavio Airoldi Multimedica Hospital, Milan, Italy N=8 Mikko SyvanneHelsinki University Central Hospital, Finland N=6 Ramon Lopez PalopHospital Universitario San Juan, Alicante, Spain N=5 Ghada Mikhail St Mary's Hospital, London, United Kingdom N=4 Philippe Mc CarthyKing's College Hospital, London, United Kingdom N=4 Francesco Romeo Tor Vergata University, Rome, Italy N=4

4. AVIO trialAngiography Vs IVUS Optimization

5. AVIO trialAngiography Vs IVUS Optimization Study Design and Time Frame n = 284 patients 1 month Clinic. F/U 6 month Clinic. F/U 9, 12, 24 month Clinical F/U IVUS guided (n= 142) Complex Lesions* R Postdilatation Angio guided (n= 142) R = randomization 49 pts were randomized to a final IVUS *Complex lesions were defined as Long lesions (>28mm), CTO, Bifurcations, Small vessels and Patients requiring 4 or more stents

6. AVIO Criteria for optimal stent expansion: 70%±10% of the cross sectional area of the inflated balloon used to post-dilate the stent The size of the NC balloon selected to post-dilate the stent is the average of the media to media diameters of the stented area measured proximally, medially and distally inside the stent. The value is rounded to the lower .00 or 0.50 mm. For values 3.5 mm or above the operator can downsize as per judgment

7. A D1 D2 STENT Stent Underexpansion Proximal Stent Distal Stent Flow chart and Measurements Performed For IVUS Optimisation Deploy Stent and Perform IVUS A in RED = Stent CSA 3.6 mm2 D1 = Max vessel Diameter (3.3mm) D2 = Min vessel Diameter (3.1mm) Optimal balloon size 3mm, target 70%

8. AVIO trialAngiography Vs IVUS Optimization Study endpoints Primary Endpoint: was post-procedure in lesion minimal lumen diameter (MLD) evaluated by corelab QCA Secondary endpoints: TLR and composite of MACE (death, MI, TVR) at 9 months Study hypothesis: MLD 2.9±0.4 for IVUS vs. 2.7±0.5 mm for angio guided DES post-dilatation .

9. AVIO trialAngiography Vs IVUS Optimization Clinical Characteristics

10. AVIO trialAngiography Vs IVUS Optimization Lesion Characteristics 1.28 lesions /patient were treated in IVUS vs 1.26 in Angio guided

11. AVIO trialAngiography Vs IVUS Optimization QCA measurements

12. Primary Study End Point In lesion MLD Final MLD in IVUS Group2.70±0.46mm Final MLD in Angio Group2.51±0.46mm Cumulative Frequency % P=0.0002 MLD (mm)

13. In lesion Acute Gain 1.93±0.59mm 1.87±0.63mm P=0.31

14. AVIO trialAngiography Vs IVUS Optimization QCA measurements in IVUS-optimized subgroup **p≤0.05 for comparison of IVUS lesions meeting AVIO criteria vs. lesions not meeting criteria

15. Primary Study End Point In lesion MLD N= 81 N= 75

16. In lesion Acute Gain N= 81 N= 75

17. AVIO trialAngiography Vs IVUS Optimization QCA measurements at FU (9 months)

18. AVIO trialAngiography Vs IVUS Optimization QCA measurements at FU (9 months)

19. AVIO trialAngiography Vs IVUS Optimization *One pt in the angio group was lost to follow-up at 9 months

20. Freedom from Cumulative MACE at 9 Months 85.9% 83.1% P= 0.47 IVUS Angio Days

21. AVIO trialAngiography Vs IVUS Optimization Stent Thrombosis (ARC Definition)

22. AVIO trialAngiography Vs IVUS Optimization Conclusions • - Our study demonstrated that a larger final MLD in lesion was obtained with IVUS guided DES postdilatation (Primary Study End-Point) • - IVUS guided postdilatation is safe procedure (no difference in 30 days MACE) • No difference in cumulative 9-months MACE between IVUS and angio guided procedures

23. Back Up slides

24. Primary Study End Point: In lesion MLD in the 2 Top Enroller Centers Center 8 Center 2 Cumulative Frequency % MLD (mm)

25. AVIO trialAngiography Vs IVUS Optimization Procedural Characteristics

26. AVIO trialAngiography Vs IVUS Optimization DES Types

27. AVIO trialAngiography Vs IVUS Optimization TLR per lesion