Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 A Prospective Randomized Trial of Proximal Microcirculatory Protection in Patients with Acute Myocardial Infarction Undergoing Primary PCI The PREPARE Trial PRoximal Embolic Protection in Acute MI and Resolution of ST-Elevation Karel T. Koch Joost D.E. Haeck, Jan G.P. Tijssen, Luc Bilodeau*, René J. van der Schaaf, José P.S. Henriques, 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 *Institut de Cardiologie de Montréal, QC, Canada † Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial RelationshipCompany Grant/Research Support: Educational Grant St. Jude Medical Disclosure statement of financial interest

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 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): Background

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 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 Proxis™ embolic protection system (St. Jude Medical, St. Paul, MN, USA)

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 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

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 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

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 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

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Primary end point ST-segment elevation resolution (STR) over time* ST-segment elevation resolution (STR) over time* Secondary end points 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

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Patient characteristics Age62 ± ± 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) Proxis n = 141 Control n = 143

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Infarct related artery RCA61%60% LAD29%29% LCx10%11% Pre-PCI TIMI graded flow 090%89% 19%8% 21% 4% Lesion characteristics Proxis n = 141 Control n = 143

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 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 * Proxis n = 141 Control n = 143

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Complete (>70%) STR (Fisher’s Exact Test) Proxis n = 141 Control n = 143 P-value *Primary endpoint

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Immediate66% (85/129) 50% (67/135) Complete (>70%) STR (Fisher’s Exact Test) Proxis n = 141 Control n = 143 P-value *Primary endpoint

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Immediate66% (85/129) 50% (67/135) min75% (91/122) 66% (86/130) min80% (101/126) 72% (93/129) min81% (100/124) 74% (97/131) min78% (98/126) 76% (100/131) 0.88 Complete (>70%) STR (Fisher’s Exact Test) Proxis n = 141 Control n = 143 P-value

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Complete STR over time Lastcontrast Time after last contrast, min Patients with complete STR, % Control Proxis P=0.009

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Immediate73 ± 2763 ± min79 ± 2175 ± min82 ± 2078 ± min82 ± 1980 ± min82 ± 1981 ± Mean % STR P-value * Proxis n = 141 Control n = 143 Mean (SD); * T-Test

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Angiographic parameters Proxis n = 141 Control n = 143 *Cochran-Armitage Test † Fisher’s Exact 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 † P-value

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 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

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 The Proxis system is feasible and safe in the setting of STEMI, and effectively retrieves embolic debris in most patients. In conclusion

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 The Proxis system is feasible and safe in the setting of STEMI, and effectively retrieves embolic debris in most patients. Complete STR was better in Proxis treated patients compared to control patients. The difference in STR immediately after PCI was highly statistically significant (p=0.009). In conclusion

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 The Proxis system is feasible and safe in the setting of STEMI, and effectively retrieves embolic debris in most patients. Complete STR was better in Proxis treated patients compared to control patients. The difference in STR immediately after PCI was highly statistically significant (p=0.009). 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

Academic Medical Center Amsterdam Interventional Cardiology Koch TCT 2008 Thank you for your attention PREPARE Trial PRoximal Embolic Protection in Acute MI and Resolution of ST-Elevation