Kirk N. Garratt, MD, FSCAI Welcome to the 11:40am Treatment of Thrombotic Lesions

Kirk N. Garratt MSc MD FSCAI FACC Associate Director, Division of Cardiac Interventions Clinical Director of Research Associate Director, Coronary Intensive Care Unit Kirk N. Garratt MSc MD FSCAI FACC Associate Director, Division of Cardiac Interventions Clinical Director of Research Associate Director, Coronary Intensive Care Unit

Disclosure Information Treatment of Thrombotic Lesions Kirk N. Garratt MSc MD, FSCAI The following relationships exist related to this presentation: The Medicines Company: (G) (AC) (SB) BMS/sanofi-aventis: (SB) Boston Scientific Corp: (G) (C) (SB) (AC) (O) Daiichi-Sankyo/Lilly: (SB) (E ): Employment (M): Management Position (I): Independent Contractor (G): Grant/Research Support (C): Consultant (SB): Speaker’s Bureau (AC): Advisory Committee (B): Board Member (O): Other Off label use of products will not be discussed in this presentation

CP prospective RCT 7,917 patients – PCI Assess outcome in thrombus vs no thrombus 2,752 with 5,165 without 6 prospective RCT 7,917 patients – PCI Assess outcome in thrombus vs no thrombus 2,752 with 5,165 without No CAT 66% CAT 34% Angiographic Trials’ Pool Singh et al: JACC 38(3):624, 2001

In-Hospital Adverse Outcome Thrombus Patients CP All patientsChi-squareP MI Death/MI Excluding pt with only vein grafts MI Death/MI All patientsChi-squareP MI Death/MI Excluding pt with only vein grafts MI Death/MI

6-Month Survival After AMI Thrombus vs Nonthrombus Lesions Probability of survival Days to 6-month MI Nonthrombus Thrombus

Things That Didn’t Work

TEC Device Acolysis Device

The EMERALD Trial Enhanced Myocardial Efficacy and Removal by Aspiration of Liberated Debris AMI <6° (N=500) Primary or rescue PTCA Native coronary or SVG PercuSurge eligible mm vessel mm vessel GpIIb/IIIa optional Cath lab 3rdgeneration 3rd generation0.028” PercuSurge distal protection PCI with PCIwithoutprotection 1º Endpoints Resolution of ST segment elevation Infarct size by tc-99m-sestamibi 2º Endpoints 2º Endpoints Myocardial blush MACE No shock

EMERALD ST Resolution Stone G, ACC 2004 Primary endpoint

EMERALD Final Infarct Size (99Tc-SPECT Scan) Stone G, ACC 2004 P=0.09 P=0.26 P=0.28

The AIMI Trial AngioJet Rheolytic Thrombectomy In Patients Undergoing Primary Angioplasty for Acute Myocardial Infarction AMI <6° (N=480) Primary PTCA Native coronary AngioJet eligible Culprit vessel >2mm Culprit vessel >2mm GpIIb/IIIa optional Cath lab AngioJet Rheolytic thrombectomy PCI with PCIwithoutthrombectomy 1º Endpoint Infarct size by tc-99m-sestamibi 2º Endpoints 2º Endpoints ST segment resolution Myocardial TIMI flow & blush LVEFMACE No shock

AiMI Trial Final Infarct Size 99Tc-SPECT From accessed 12/4/08www.medscape.com

Comparison of AngioJET Rheolytic Thrombectomy Before Direct Infarct Artery STENTing with Direct Stenting Alone in Patients with Acute Myocardial Infarction: the JETSTENT trial David Antoniucci on behalf of the JETSTENT Investigators

Co-Principal Investigators David Antoniucci, MD; Florence Antonio Colombo, MD; Milan Clinical Event Adjudication Committee Issam Moussa, M.D., Weill Cornell Medical Center, NYC Gian Battista Danzi, M.D., Ospedale Maggiore, University of Milan, Milan Carlo Di Mario, M.D., PhD, Royal Brompton Hospital, London Data Management and Monitoring Director: Maria Cristina Jori, M.D. Mediolanum Cardio Research, Milan ECG Core Laboratory Serenella Castelvecchio, M.D. Mediolanum Cardio Research, Milan Angiographic Core Laboratory Maria Antonietta Bonardi, M.D. Mediolanum Cardio Research, Milan Nuclear Scan Core Laboratory Prof. Roberto Sciagrà, University of Florence, Florence Steering Committe D Antoniucci, A Colombo, F-J Neumann, A Rodriguez, A Stabile, J Gustafson Sponsor: Medrad Interventional/Possis

After angiography and IRA wiring: thrombus grade 3 to 5 Pts with STEMI admitted within 12 hours from symptom onset  Lysis  Stroke < 30 days  Surgery < 6 weeks  Pre-stented IRA Rheolytic Thrombectomy +DSDirect Stenting (DS) Study Design Randomization 1:1 N = 500

Technique for AngioJet Use and DS Single pass anterograde technique (activate AngioJet proximal to thrombus) Angiographic check after first AngioJet pass. Temporary pacemaker strongly discouraged. Balloon pre-dilation strongly discouraged. DS had to be attempted in all cases in both arms. Routine Abciximab in both arms.

JETSTENT TRIAL  Primary surrogate end points: Early ST-segment resolution (≥ 50% ST segment elevation reduction at 30 minutes) Infarct size (1-month 99m Tc sestamibi scintigraphy)  Clinical end points: MACE at 1, 6, and 12 months Death and Readmission for CHF at 12 months  Secondary surrogate end points: TIMI flow, cTFC, and TIMI blush

Baseline Angiographic Characteristics RTDS n=256 n=245 p value  Multivessel disease114 (44)95 (39).192  IRA.483 LAD107 (42)91 (37) RCA112 (44)120 (49) LCx37 (14)34 (14)  RVD (mm)2.94 [ ] 2.91 [ ].670  Pre-wiring TIMI flow /254 (83.5)203/242 (83.9).899  Post-wiring TIMI flow /231 (61.5) 129/222 (58.1).465  Thrombus grade (1.4)3 (1.4) 373 (32.5)80 (37.4) 483 (37.4)79 (36.9) 563 (28.4)52 (24.3)

RTDS n=256n=245 p value  ER-PCI (min)34 [15-67]31 [18-60].727  Procedural time (min) 59.5 [ ] 46 [35-60] <.001  Predilation before RT5/246 (2)  TIMI flow 3 after RT159/ 222 (72)  Predilation before stenting25 (9.8)34 (13.9).149  Stent per pt 1.26 ± ±  Mean stent length (mm) 23.7 ± ±  Abciximab249 (97)239 (98).841  Procedural success237 (93)229 (93).696 Procedural Characteristics

Surrogate Endpoints RT DS p value n=246n=240 STR ≥ 50% at 30 min 211 (85.8)189 (78.8).043 n=217n=208 Infarct Size (%)11.8 [ ] 12.7 [ ].398 n=252n=241 Final TIMI 3 flow 203 (80.6) 207 (85.9).113 n=228n=216 cTFC 20 [ ] 20 [ ].357 n=215n=211 Blush grade (8)11 (5) 243 (20)33 (16) (72)167 (79)

One-Month Outcome P = 0.050

6-Month Outcome RT DS

Conclusions  AngioJet rheolytic thrombectomy before direct IRA stenting as compared to direct stenting alone is associated with: o Better myocardial reperfusion (higher rate of early STR) o Improved 6-month clinical outcome (lower MACE rate)  The results of the JETSTENT trial support the routine use of AngioJet rheolytic thrombectomy in AMI patients with evidence of thrombus.

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What’s Really Made A Difference

TAPAS Trial Design

TAPAS Myocardial Blush Grade

TAPAS ST Segment Resolution

TAPAS Cardiac Death At One Year

TAPAS Cardiac Death or Non-fatal MI At One Year

Meta-analysis of Aspiration Thrombectomy Device Use Mortality at 30 Days De Luca G, Eur Heart J 2008 (Sept e-publication)

Meta-analysis of Aspiration Thrombectomy Device Use De Luca G, Eur Heart J 2008 (Sept e-publication)

Meta-analysis Of Distal Protection Or Thrombectomy Device Use Stone et al: Circulation 2008; 118:552

Treatment of Thrombus Containing Lesions Thrombotic lesions have increased risk Thrombotic lesions have increased risk Adjunctive devices largely disappointing Adjunctive devices largely disappointing May be some benefit for rheolytic thrombectomy in bulky thrombus May be some benefit for rheolytic thrombectomy in bulky thrombus Aspiration thrombectomy as routine adjunct to thrombotic lesions is standard of care for ACS/STEMI Aspiration thrombectomy as routine adjunct to thrombotic lesions is standard of care for ACS/STEMI