Transcript Results of CRYSTAL AMI: A Pilot Trial Before INFUSE AMI, the Concept and Evolution in Thrombus Management Saihari Sadanandan, MD, FACC, FASE, Dip.

Results of CRYSTAL AMI: A Pilot Trial Before INFUSE
AMI, the Concept and Evolution in Thrombus
Management
Saihari Sadanandan, MD, FACC, FASE, Dip. CBNC, FSCAI
Associate Professor of Clinical Medicine
Director, Vascular Interventions
Division of Cardiology
IU- Health
Indiana University
Indianapolis
Disclosure - I
Speaker Bureau – Sanofi Aventis
Bristol Myers Squibb
Daichi Sankyo/Lilly
Educational Grant from Atrium Medical
towards IRB fees to collect data on the case
Studies
CRYSTAL – AMI slide courtesy – R. Dave, MD
Acute Inferior MI: Primary PCI for STEMI
Primary PCI for STEMI: Predilation and Stent
Distal Embolization during primary PCI for STEMI
5 year outcomes of No-reflow
during Primary PCI for STEMI
•N = 1406
•Pts with STEMI undergoing PCI
•No reflow defined as TIMI <3 flow or
TMPG 0-1 after successful PCI
•Occurred in 30% of pts
• 7-14 day infarct size 15% vs. 8% p<0.001
•5-year mortality 18.2% vs. 9.5%, p < 0.001
Ndrepepa G, et al.. J Am Coll Cardiol. 2010;55:2383-2389.
Distal embolization and small distal
vessel cutoff is neither infrequent nor
benign!!!!
•Occurs in about 15% of patients undergoing PCI for STEMI
•Associated with larger infarct size, lower LVEF and
increased long term Mortality
(Eur H J 2002:23-1112-17
Distal embolization during Primary PCI for STEMI
No DE
n = 151 (85%)
DE
n = 27 (15%)
P Value
51 ± 9
42 ± 14
0.005
Cardiac
enzyme
847 ± 631
1612 ± 1008
0.001
Mortality
15 (9%)
12 (44%)
< 0.001
N=178
LVEF (%)
(Eur H J 2002:23-1112-17)
(Eur H J 2002:23-1112-17
IMPACT OF
MYOCARDIAL BLUSH
GRADE
TIMI Myocardial Perfusion (TMP) Grades
8
TMP Grade 3
Normal ground-glass
appearance of blush.
Dye mildly persistent
at end of washout.
TMP Grade 2
Dye strongly persistent
at end of washout.
Gone by next injection.
6
TMP Grade 1
Stain present.
Blush persists
on next injection.
TMP Grade 0
No or minimal blush.
6.2%
5.1%
P=0.05
4.4%
4
2
0
2.0%
n=203
n=46
Adapted from Gibson CM, et al. Circulation. 2000;101:125-130.
n=79
n=434
Myocardial Perfusion After Primary PCI is the Strongest
Predictor of Mortality independently from IRA reopening
Final Blush Score (patients with final TIMI 3 flow)
Cumulative Survival (%)
100
95
3
90
2
85
3
2
0/1
80
75
0
2
Blush 1-Year Mortality
6.8%
P=0.004
13.2%
18.3%
4
6
8
0/1
10
12
Effects of Thrombo embolization during Primary PCI
No reflow/ slow flow
Poor TIMI flow
Thrombus
Poor MBG
Larger Infarct size
Meta-Analysis of
Various Devices—Mortality
Adjunctive device prior to PCI
PCI alone
P = 0.050
5.3
6
P = 0.018
Mortality, %
4.4
P = 0.69
4
2.8
2.7
3.1
2
0
Catheter thrombus
aspiration
Mechanical
thrombectomy
Bavry AA, Kumbhani D, Bhatt DL. Eur Heart J. 2008;29:2989-3001.
Embolic
protection
3.4
TAPAS one year outcome:
Myocardial blush grade and death
Death/reinfarction P= 0.001
Svilaas T et al. NEJM 2008;358-557 - FZ 2008-9
Myocardial blush grade
FZ 2008-12
Burzotta et al. European Heart Journal (2009) 30, 2193-2203
Thrombectomy ± IIb/IIIa inhibitors
MORTALITY
8%
7.4%
P=0.02
6%
5.0%
4.8%
4%
3.3%
2%
IIb/IIIa inhib
Thrombectomy
-
IIb/IIIa inhib
Thrombectomy
+
-
IIb/IIIa inhib
Thrombectomy
–
+
IIb/IIIa inhib
Thrombectomy
+
+
Summary of Current Limitations in STEMI PCI
• No optimal method of thrombus management
• Once embolization occurs in primary PCI , it is a
challenging scenario
• Higher MACE, Infarct size with poor MBG
• Aspiration catheters are good, but not uniformly
effective.
• There may be a synergistic effect between
thrombectomy and GP-IIBIIIA receptor inhibitors
HOW CAN WE IMPROVE ON THIS FURTHER IN
STEMI PCI?
COMBINE THE MECHANICAL APPROACH WITH
PHARMACOLOGY
-(INTRACORONARY DRUG)
MINIMIZE BLEEDING & MAXIMIZE
DETHROMBOSIS
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.
Clearway Catheter and Intracoronary Abciximab
Localized Drug Delivery via ClearWay for Pharmacological Thrombectomy
and Prevention of Distal Embolization
During inflation, drug is being infused through the
microporous balloon pores while blood flow is
occluded, maximizing drug availability without
substantial dilution by the systemic circulation.
Occlusion
Containment of the treatment zone provides
extended residence time to help local drug
bioavailability, concentration and dose
Containment
Controlled infusion at 1-4 ATM throughout the
entire length of the targeted treatment zone
provides increased residence time and uptake
Infusion
IC vs. Clearway Abciximab: The
Coctail Study
Tamburino, Capodanno, et al. J Cardiovasc Med 2009
Pre ReoPro through ClearWay
Post ReoPro through Clearway
Coctail study: Change in Thrombus score
40
37.9
35
30
P=0.002
25
20
15
10
4.25
5
0
ClearWay Inf.
N= 20
Guid. Cath. Inf.
N =21
Tamburino, Capodanno, et al. J Cardiovasc Med 2009
Coctail study: Final TIMI MBG
2.8
2.78
2.75
P=0.24
2.7
2.65
2.6
2.56
2.55
ClearWay Inf.
Guid. Cath. Inf.
2.5
2.45
ClearWay Inf.
Guid. Cath. Inf.
N 21
N 20
Tamburino, Capodanno, et al. J Cardiovasc Med 2009
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
CRYSTAL- AMI: Demographics (N=48)
Treatment arm
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)
18
16
16
14
12
12
10
9
8
Manual
Angiojet
7
None
6
4
2
2
2
IC
IV
0
(n = 25)
(n = 23)
TIMI Flow Comparison (N=48)
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
(N=48)
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 (N=48)
Readmissions
IC
0
IV
2
Death
0
1
Conclusions
• Our understanding of evaluation of surrogate markers which directly
correlates to Mortality and Myocardial preservation has improved
significantly
• Improving myocardial preservation also has profound economic
impacts: low cost of care, better QOL, less need for ICD
• Localized superselective drug delivery (GP 2b3a inhibitors and
vasodilators) with ClearWay as a stand alone device or when
combined with Aspiration devices significantly improves MBG
• Series of data already promising, INFUSE AMI is underway…