Improving outcome of STEMI PCI: Preliminary Results of Crystal AMI trial Rajesh M. Dave, MD Principal investigator on behalf of Crystal AMI Investigators Harrisburg, PA

Disclosure Atrium Medical: Consultant, Research support, Training and speaking Honorarium Eli Lilly: Speaker Honorariums

Background Distal embolization of atherothrombotic material remains a significant challenge during STEMI PCI Consequences: No Reflow, Poor TIMI and MBG grade, Higher MACE, Late ST if DES placed on thrombus Long term mortality is higher in patients with large degree of distal embolization Aspiration thrombectomy has shown improvement in MBG grades, however, it is not universally effective Hence, new modalities to address thrombus burden are investigated Many studies have demonstrated benefit of IC Abciximab- reduce no reflow, infarct size, Improved TIMI flow and Blush Scores

N= 2,118 consecutive STEMI patients I II III TIMI Flow: Blush Scores: Is the myocardial blush grade scored by the operator during primary percutaneous coronary intervention of prognostic value in patients with ST elevation myocardial infarction in routine clinical practice? N= 2,118 consecutive STEMI patients One Year Mortality in Primary PCI I II III TIMI Flow: 46.3% 25% 8.4% 6.6% Blush Scores: 24.0 9.7 5.8% 4.3% Despite TIMI-3 Flow, Normal Blush in ONLY 45% Myocardial Blush Grade: I II III Mortality in pts. w/TIMI-3 Flow P value: < .001 17% 10 6% 4% Further evidence of impaired myocardial perfusion despite normal epicardial flow comes from the work of Greg Stone looking at myocardial blush scores. These data corroborated the earlier findings of van’t Hof. In patients with normal TIMI 3 flow, only 29% had a normal myocardial blush grade of 3. So despite having normal epicardial coronary blood flow, the myocardium is not adequately perfused in these patients, most likely due to microvascular obstruction. Furthermore, these data show a correlation between poor blush scores and an increased risk for mortality. Normal epicardial flow does not necessarily correlate with normal Perfusion. Microvascular dysfunction caused by embolization, likely results in impaired myocardial perfusion. Kampinga MA, Nijsten MWN, Gu YL, et al. Circ Cardiovasc Interv. 2010;3:216-223.

Meta Analysis of IC Versus IV Abciximab administration of peer reviewed studies (N=2,301) 997 STEMI, 1304 NSTEMI Hansen et al. Journal of Invasive Cardiology Vol 22; 6. June 2010. 278-282.

IC Abciximab delivery with ClearWay™ Therapeutic Drug Delivery Balloon: Concept ClearWay™ Drug Delivery Balloon: Allows super-selective IC delivery of Abciximab in higher concentration versus IV Superiority to Guide catheter Abciximab delivery: Prevents loss of drug in aorta, no wire exchange needed Higher residence time of drug allows expression of disaggregating and anti-inflammatory properties of Abciximab 1 Hypothesis: Delivery of IC Abciximab with ClearWay™ leads to better ST resolution, higher MBG, Improved TIMI flow and smaller Infarct size than IV Abciximab during STEMI PCI CRYSTAL AMI: Pilot proof of concept trial, not powered to show statistical differences 1. Prati et al., COCTAIL Study, JACC, 2010.

CRYSTAL AMI: Study Design Single center, prospectively randomized STEMI within 6 hours, Heparin, 600mg Clopidogrel (n=50) R 1:1 IV Abciximab ClearWay™ IC Abciximab PCI as per standard of care, Evaluate MBG, TIMI flow, ST Resolution, LV Function at Discharge 30 day follow up, Echo, Resting Sestamibi

Demographics Treatment arm N=48 IC =25 IV=23 Male/Female M=23, F=2 Age 62 + 25 65 + 23 HTN 14 Angina 5 2 CHF 1 Prior PCI 6 CABG 3 DM 8 Lipids 9 Smoking C=9, F=2 C=6, F=0

Manual/Mechanical Extraction catheter use (discretion of operator)

TIMI Flow Comparison in first 48 patients 96% TIMI Flow (n = 25) (n = 23)

92% of IC versus 86% of IV patients Primary Endpoint: TIMI Myocardial Blush Grade (MBG) >2 scores comparison in first 48 patients 92% of IC versus 86% of IV patients MBG (n = 25) (n = 23)

MBG 3 and ST Resolution Rates comparison 80% 70% 72% 52% (n = 25) (n = 23) In Tapas, MBG 3 was only achieved in 45% of patients in extraction arm (identical to IV Abciximab group), but was directly linked to 5 times increase in mortality. IC Abciximab Administration through ClearWay™ has resulted in 72% of patients leaving the lab with a blush score of 3.

Clinical Outcomes IC IV Readmissions 2 Death 1

50yomale with Anterior STEMI

ClearWay 1.5X20 Abciximab bolus

Flow restored after ClearWay

Xience V Stent Reinsertion of ClearWay for Localized Nipride administration

Conclusions IC Abciximab super-selective delivery is safe and effective delivered via ClearWay™ drug delivery balloon, and produced higher MBG scores (more achieved MBG 3 75% vs 45% ) and trend towards higher ST-Segment resolution (80% vs 70% ns) This study supports the findings of previous study such as TAPAS, where MBG of 3 was achieved in only 45% of patients receiving aspiration catheter and IV Abciximab. An equal number of patients received manual thrombus aspiration in each study arm (65%) suggesting a synergistic effect with IC Abciximab super- selective delivery with ClearWay™