Transcript Slides - Clinical Trial Results

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
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
TIMI Flow:
Blush Scores:
0
I
II
III
46.3%
25%
8.4%
6.6%
24.0
9.7
5.8%
4.3%
Despite TIMI-3 Flow, Normal Blush in ONLY 45%
Myocardial Blush Grade:
Mortality in pts. w/TIMI-3 Flow
P value: < .001
0
I
II
III
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.
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
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
1
5
3
96%
TIMI Flow
3
82%
2
1
3
24
19
2
1
0
16
17
4
1
IC TIMI Pre
IC TIMI Post
(n = 25)
IV TIMI Pre
IV TIMI Post
(n = 23)
Primary Endpoint: TIMI Myocardial Blush Grade (MBG) >2
scores comparison in first 48 patients
92% of IC versus 86% of IV patients
MBG
0
1
92%
7
3
18
1
2
2
86%
12
2
1
17
0
18
8
5
1
3
1
IC Blush Pre
(n = 25)
IC Blush Post
IV Blush Pre
IV Blush Post
(n = 23)
MBG 3 and ST Resolution Rates comparison
21
80%
18
18
70%
72%
12
52%

IC Abciximab
IV Abciximab
(n = 25)
(n = 23)
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.
Clinical Outcomes
IC
IV
Readmissions
0
2
Death
0
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 STSegment 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™