results of crystal ami: a pilot trial before infuse ami, the concept and evolution in thrombus...
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Results of CRYSTAL AMI: A Pilot Trial Before INFUSE AMI, the Concept and Evolution in Thrombus Management
Saihari Sadanandan, MD, FACC, FASE, Dip. CBNC, FSCAIAssociate Professor of Clinical Medicine
Director, Vascular InterventionsDivision of Cardiology
IU- HealthIndiana University
Indianapolis
Disclosure - I
Speaker Bureau – Sanofi AventisBristol Myers SquibbDaichi Sankyo/Lilly
Educational Grant from Atrium Medicaltowards 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 norbenign!!!!
• 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
(Eur H J 2002:23-1112-17
N=178No DE
n = 151 (85%)DE
n = 27 (15%)P Value
LVEF (%) 51 ± 9 42 ± 14 0.005
Cardiac enzyme
847 ± 631 1612 ± 1008 0.001
Mortality 15 (9%) 12 (44%) < 0.001
(Eur H J 2002:23-1112-17)
Distal embolization during Primary PCI for STEMI
IMPACT OF MYOCARDIAL BLUSH GRADE
0
2
4
6
8
Mo
rta
li ty
(%
) 6.2%
4.4%
2.0%
n=203 n=46 n=434
TMP Grade 3
P=0.05
n=79
5.1%
Normal ground-glassappearance of blush.Dye mildly persistent
at end of washout.
Dye strongly persistentat end of washout.
Gone by next injection.
Stain present.Blush persists
on next injection.
No or minimal blush.TMP Grade 2 TMP Grade 1 TMP Grade 0
Adapted from Gibson CM, et al. Circulation. 2000;101:125-130.
TIMI Myocardial Perfusion (TMP) Grades
80
85
90
953
2
0/1
100C
um
ula
tive
Su
rviv
al (
%)
0 2 4 6 8 10 1275
Final Blush Score (patients with final TIMI 3 flow)
Blush 1-Year Mortality32
0/1
6.8%13.2%18.3%
P=0.004
Myocardial Perfusion After Primary PCI is the Strongest Predictor of Mortality independently from IRA reopening
No reflow/ slow flow Poor TIMI flow
Poor MBG Larger Infarct size
Thrombus
Effects of Thrombo embolization during Primary PCI
2.7
5.3
3.1
4.4
2.83.4
0
2
4
6
Adjunctive device prior to PCI PCI alone
Meta-Analysis of Various Devices—Mortality
Bavry AA, Kumbhani D, Bhatt DL. Eur Heart J. 2008;29:2989-3001.
Mechanical thrombectomy
Catheter thrombus aspiration
Embolic protection
P = 0.018
P = 0.050
P = 0.69
Mo
rta
lity,
%
FZ 2008-12
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
Burzotta et al. European Heart Journal (2009) 30, 2193-2203
Thrombectomy ± IIb/IIIa inhibitors
7.4%
5.0% 4.8%
3.3%
IIb/IIIa inhib -Thrombectomy -
IIb/IIIa inhib +Thrombectomy -
IIb/IIIa inhib –Thrombectomy
+
IIb/IIIa inhib +Thrombectomy
+
4%
2%
8%
6%
MORTALITY
P=0.02
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
Occlusion
Containment
Infusion
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.
Containment of the treatment zone provides extended residence time to help local drug bioavailability, concentration and dose
Controlled infusion at 1-4 ATM throughout the entire length of the targeted treatment zone provides increased residence time and uptake
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
37.9
4.25
0
5
10
15
20
25
30
35
40
ClearWay Inf. Guid. Cath. Inf.
P=0.002
N= 20 N =21
Tamburino, Capodanno, et al. J Cardiovasc Med 2009
Coctail study: Final TIMI MBG
2.78
2.56
2.45
2.5
2.55
2.6
2.65
2.7
2.75
2.8
ClearWay Inf. Guid. Cath. Inf.
ClearWay Inf.Guid. Cath. Inf.
P=0.24
N 20N 21Tamburino, Capodanno, et al. J Cardiovasc Med 2009
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)
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)
16
12
2 2
7
9
0
2
4
6
8
10
12
14
16
18
IC IV
Manual
Angiojet
None
(n = 25) (n = 23)
TIMI Flow Comparison (N=48)
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 Flow
96%
Primary Endpoint: TIMI Myocardial Blush Grade (MBG) >2 (N=48)
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 (N=48)
IC IVReadmissions 0 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…