Improving outcome of STEMI PCI: Preliminary Results of Crystal AMI

trial

Rajesh M. Dave, MDPrincipal investigator on behalf of Crystal

AMI InvestigatorsHarrisburg, PA

DisclosureAtrium Medical: Consultant, Research

support, Training and speaking HonorariumEli Lilly: Speaker Honorariums

BackgroundDistal 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

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?

One Year Mortality in Primary PCI 0 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: 0 I II III

Mortality in pts. w/TIMI-3 FlowP value: < .001

17% 10 6% 4%

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.

N= 2,118 consecutive STEMI patients

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 DesignSingle center, prospectively randomized

IV Abciximab ClearWay™ IC Abciximab

R 1:1

PCI as per standard of care, EvaluateMBG, TIMI flow, ST Resolution, LV Function at Discharge

30 day follow up, Echo, Resting Sestamibi

STEMI within 6 hours, Heparin, 600mg Clopidogrel (n=50)

DemographicsTreatment arm N=48

IC =25 IV=23

Male/Female M=23, F=2 M=18, F=5

Age 62 + 25 65 + 23

HTN 14 14

Angina 5 2

CHF 1 0

Prior PCI 6 2

CABG 3 1

DM 8 6

Lipids 14 9

Smoking C=9, F=2 C=6, F=0

Manual/Mechanical Extraction catheter use (discretion of operator)

(n = 25) (n = 23)

TIMI Flow Comparison in first 48 patients

16

1

17

3 1

5

2

4

1

24

3

19

IC TIMI Pre IC TIMI Post IV TIMI Pre IV TIMI Post

3

2

1

0

82%

(n = 25) (n = 23)

TIMI Flow96%

Primary Endpoint: TIMI Myocardial Blush Grade (MBG) >2 scores comparison in first 48 patients

17

1

18

72

3

1

5

2

8

0

18

1

12

IC Blush Pre IC Blush Post IV Blush Pre IV Blush Post

3

2

1

0

92%86%

1

(n = 25) (n = 23)

MBG

92% of IC versus 86% of IV patients

MBG 3 and ST Resolution Rates comparison

18

12

21

18

IC Abciximab IV Abciximab

MBG 3

ST Resolution

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.

(n = 25) (n = 23)

72%

80%

52%

70%

Clinical Outcomes

IC IV

Readmissions 0 2

Death 0 1

50yomale with Anterior STEMI

ClearWay 1.5X20Abciximab bolus

Flow restored after ClearWay

Xience V StentReinsertion of ClearWay forLocalized 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™