1. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Within the past 12 months, our institution has had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial RelationshipCompany Grant/Research Support: Unrestricted educational grant St. Jude Medical Disclosure statement of financial interest

2. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Randomized Comparison of Primary PCI with Combined Proximal Embolic Protection and Thrombus Aspiration versus Primary PCI Alone in STEMI The PREPARE Trial PRoximal Embolic Protection in Acute MI and Resolution of ST-Elevation Joost D.E. Haeck Karel T. Koch, Luc Bilodeau*, Jan G.P. Tijssen, René J. van der Schaaf, José P.S. Henriques, Wim. J. Rohling, Allard van der Wal, Jan Baan Jr., Marije M. Vis, Jan J. Piek, Mitchell W. Krucoff †, Robbert J. de Winter. Academic Medical Center - University of Amsterdam, The Netherlands *Montréal Heart Institute, QC, Canada † Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA

3. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Inadequate myocardial reperfusion relates to prognosis, even in the presence of adequate epicardial flow. Embolization of atherothrombotic material plays a crucial role in microvascular obstruction and impaired myocardial perfusion. The Proxis™ device is a combined system of proximal embolic protection and thrombus aspiration. The device has been shown feasible and safe in primary PCI *. The PREPARE Trial was designed to evaluate primary PCI with the Proxis system compared to primary PCI alone. *Koch KT et al. Rev Cardiovasc Med. 2007;8(3): 160-6 Background

4. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Proxis embolic protection system Full length flexible catheter 6F and 7F GC compatible Sealing balloon at the tip CO 2 based inflation device Deployed proximal to target lesion before crossing Inflation of balloon suspends antegrade flow during lesion intervention Stagnated blood and emboli, liberated during intervention are retrieved by gentle aspiration Proxis™ embolic protection system (St. Jude Medical, St. Paul, MN, USA)

5. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 PRoximal Embolic Protection in Acute MI and Resolution of ST-ElevationPRoximal Embolic Protection in Acute MI and Resolution of ST-Elevation Investigator-initiated randomized trialInvestigator-initiated randomized trial Comparison of primary PCI with Proxis system versus primary PCI aloneComparison of primary PCI with Proxis system versus primary PCI alone Open trial with blinded evaluation of end pointsOpen trial with blinded evaluation of end points Participation of 2 centersParticipation of 2 centers 140 patients in each study arm140 patients in each study arm PREPARE Trial

6. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Inclusion criteria Consecutive STEMI patients ≤ 6 hConsecutive STEMI patients ≤ 6 h ST-segment elevation ≥ 2 mm in ≥ 2 leadsST-segment elevation ≥ 2 mm in ≥ 2 leads TIMI flow grade 0 to 1 at first angiogramTIMI flow grade 0 to 1 at first angiogram Coronary anatomy suitable for ProxisCoronary anatomy suitable for Proxis ECG suitable for ST-segment resolution evaluationECG suitable for ST-segment resolution evaluation Exclusion criteria Recurrence of MI in same areaRecurrence of MI in same area Prior CABG or lyticsPrior CABG or lytics Patient selection

7. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 UFH 70 U/kg ASA 300 mg Clopidogrel 600 mg Continuous ST Holter Coronary angiogram STEMI ≤ 6 h Primary PCI alone Clinical follow up at 30 days Primary PCI with Proxis PREPARE Trial Study flow chart R 24 h

8. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Primary end point ST-segment elevation resolution (STR) over time* ST-segment elevation resolution (STR) over time* Secondary end points ST-segment curve area ST-segment curve area TIMI graded flow TIMI graded flow Myocardial blush grade Myocardial blush grade Angiographic signs of distal embolization Angiographic signs of distal embolization Composite of death, MI, TVR, and stroke at 30 days Composite of death, MI, TVR, and stroke at 30 days End points *Duke Clinical Research Institute Core Lab

9. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Patient characteristics Age62 ± 11 59 ± 11 Male 80%80% Family history CAD35%38% Hypercholesterolemia21%13% Current smoking 50%65% Hypertension31%23% Diabetes12%6% Previous MI6%9% Multivessel disease33%31% Symptoms to balloon (min) 170 153 Proxis n = 141 Control n = 143 * * *p≤0.03

10. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Proxis n = 141 Control n = 143 Infarct related artery RCA61%60% LAD29%29% LCx10%11% Pre-PCI TIMI graded flow 090%89% 19%8% 21% 4% Lesion characteristics

11. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Proxis n = 141 Control n = 143 Procedural characteristics *P<0.05; IQR interquartile range Procedural success100%99% Proxis placed94%─ Predilatation and stenting87%76% Direct stenting 11%19% Balloon angioplasty 3% 6% GP IIb/IIIa receptor antagonists 43%35% Additional thrombus aspiration 6%6% Pathology confirmed thrombus 75% ─ Puncture to balloon (min) Median 17 14* IQR 13-2310-18 * Proxis n = 141 Control n = 143

12. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Immediate66% (85/129) 50% (67/135) 0.009 30 min74% (96/130) 64% (87/135) 0.11 60 min80% (101/126) 72% (93/129) 0.14 90 min81% (100/124) 74% (97/131) 0.23 120 min78% (98/126) 76% (100/131) 0.88 Complete (≥70%) STR (Fisher’s Exact Test) Proxis n = 141 Control n = 143 P-value

13. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Complete STR over time Lastcontrast 40 50 60 70 80 90 30 60 90120 Time after last contrast, min Patients with complete STR, % P=0.009 Control Proxis

14. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 ST- resolution % Immediate73 ± 2763 ± 320.009 Immediate73 ± 2763 ± 320.009 30 min78 ± 2174 ± 240.18 30 min78 ± 2174 ± 240.18 60 min82 ± 2078 ± 210.27 60 min82 ± 2078 ± 210.27 90 min82 ± 1980 ± 210.17 90 min82 ± 1980 ± 210.17 120 min 82 ± 19 81 ± 20 0.48 120 min 82 ± 19 81 ± 20 0.48 ST- curve area ** (µV/min) Median5192 62500.037 Median5192 62500.037 IQR(3793-7626) (4221-9186) IQR(3793-7626) (4221-9186) Continuous ST-recovery parameters P-value * Proxis n = 141 Control n = 143 Mean (SD); * T-Test * * Area under ST-deviation versus time trend curve is from last contrast to 3 hours after procedure * * Area under ST-deviation versus time trend curve is from last contrast to 3 hours after procedure

15. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Procedural parameters Proxis n = 141 Control n = 143 *Cochran-Armitage Test † Fisher’s Exact Test ‡ Mann Whitney U Test Post-PCI TIMI graded flow 393%87% 27%11%0.06 * 0-10%2% 0-10%2% Myocardial blush grade 381%83% 216%11%0.93 * 0-14%6% 0-14%6% Distal embolization (yes/no)10%14%0.36 † Infarct size by peak CK-MB (μg/L) Median2042460.22 ‡ IQR136-378154-413 P-value †

16. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Debris confirmed by pathology75% (84/112) Before stenting87% (73/84) Both before and after stenting35% (29/84) Only after stenting13% (11/84) Only thrombus50% (42/84) Thrombus and plaque-components49% (41/84) Only plaque-components1% (1/84) Pathology results Proxis n = 112

17. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 Death22 MI23 TVR36 Stroke01 MACCE * 6 (4%) 10 (7%) no complications at Proxis landing zone no complications at Proxis landing zone Clinical events at 30 days Proxis n = 141 Control n = 143 For descriptive purposes only; no statistical comparisons done *ARC MACCE definition Circ. 2007; 115: 2344–2351

18. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 All patients66% (85/129) 50% (67/135) 0.009 Infarct-related artery Anterior42% (16/38) 18% (7/40) 0.03 Non-anterior76% (69/91) 63% (60/95) 0.08 Baseline thrombus Yes65% (64/98) 50% (46/92) 0.04 No68% (21/31) 49% (21/43) 0.15 Symptom onset to balloon < 3 hours68% (47/69) 49% (43/87) 0.02 ≥ 3 hours63% (38/60) 50% (24/48) 0.18 GP IIb/IIIa antagonists Yes56% (29/52) 28% (13/46) 0.008 No 72% (56/77) 61% (54/89) 0.14 P-value Proxis n = 129 Control n = 135 (Fisher’s Exact Test) Subgroup analysis complete STR at last contrast

19. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 The Proxis system is feasible and safe in the setting of STEMI, and effectively retrieves embolic debris in most patients. Complete STR was faster and more frequent in Proxis treated patients, with reduction of ECG injury current over time, compared to control patients. The results of the PREPARE trial suggest that primary PCI with combined proximal embolic protection and aspiration leads to better immediate microvascular flow in STEMI patients. In conclusion

20. Academic Medical Center Amsterdam Interventional Cardiology JACC Intv. 2009 Oct; 2 (10): 934-43 PREPARE Trial PRoximal Embolic Protection in Acute MI and Resolution of ST-Elevation Thank you for your attention K.T.Koch@amc.uva.nl