1. Infused AMI: Intracoronary IIb/IIIa Infusion for STEMI
Brij Maini MD, FACC Chair Structural Heart Program Co-Chair Cardiovascular Research Pinnacle Health System, Harrisburg, PA

2. Brijeshwar S. Maini, MD DISCLOSURES Consulting Fees
Atrium Medical Corporation, Abiomed, Inc
Grants/Contracted Research
Abbott Vascular, Abiomed, Inc., AGA Medical Corporation, Cordis, a Johnson & Johnson company, ev3, Inc., InfraReDx, Inc, Medtronic CardioVascular, Inc.
Honoraria
Abiomed, Inc., Abbott Vascular, ev3, Inc., Medtronic CardioVascular, Inc.
I intend to reference unlabeled/unapproved uses of drugs or devices in my presentation.
I intend to reference unapproved devices in clinical trials such as Impella, LAA devices such as Watchman, thoracic and abdominal stentgrafts in trials including endostapling devices.

3. Coronary Thrombosis in acute coronary syndrome
Plaque rupture %
Plaque erosion %
Calcified nodule
2-7%
IMAGE COURTESY: Virmani, R. et al. J Am Coll Cardiol 2006

4. IWMI
stent
Distal Embolization
Rxed with aspiration only

5. How Big Is the Clot?

6. Re-perfusing the capillaries restores blood flow to the
Reperfusion of the Capillaries
After acute myocardial infarction (AMI), the immediate therapeutic goal is to establish patency of the infarcted related artery. The successful restoration of epicardial coronary artery patency, however, does not necessarily translate into improved tissue perfusion.
Copyright CM Gibson
Copyright CM Gibson
Re-perfusing the capillaries restores blood flow to the
muscle bed preventing damage to the heart muscle.

7. Macroscopic distal embolization
Patients with distal embolization had lower incidence of ST resolution, poor blush grades, larger infarcts, and significantly higher long term mortality. N=178.
Henriques, et al. Eur Heart J, 2002; 23: 1112–1117. 7

8. Angiography is a Poor Tool for Thrombus Detection
Angiography underestimates the presence of thrombus, particularly in the setting of total occlusions.
A recent study of Lower extremity patients with <6 months of symptoms showed that via IVUS, thrombus was present 94% of the time, whereas under angiography, it was only present in 11% of patients. Shammas et al. Prevalence of thrombus in patients with a recent history of claudication or rest limb pain: An intravascular assessment. New Cardiovascular Horizions Sept., 2007.

9. Mortality is three to four times higher In patients with MBG 0-2
Tissue Level Perfusion In CADILLAC Trial
N=1,301 patients
Mortality is three to four times higher
In patients with MBG 0-2
even with TIMI3
Costantini, C. O. And GW Stone et al. J Am Coll Cardiol 2004;44:

10. Chao-Wei Hwang, MD, PhD, MIT (Circulation. 2005;111:1619-1626.
Thrombus apposed on stents creates large variations in drug uptake, making it highly variable, unless the clot can be adequately controlled or removed.

11. Available now online from European Heart Journal 11

12. Thrombectomy ± IIb/IIIa inhibitors4% 2% 8% 6%
MORTALITY
7.4%
P=0.02
5.0%
4.8%
3.3%
IIb/IIIa inhib -
Thrombectomy -
IIb/IIIa inhib +
Thrombectomy -
IIb/IIIa inhib –
Thrombectomy +
IIb/IIIa inhib +
Thrombectomy + 12

13. PRE-PCI SUBGROUPS Risk of death DIABETES IIb/IIIa INHIBITORS
TIME TO REPERFUSION
INFARCT RELATED ARTERY
TIMI FLOW
Thrombectomy better
Standard PCI better 13

14. CONCLUSIONS
The present pooled analysis of individual patient data from 11 STEMI trials shows that:
- Thrombectomy (in particular when performed by manual thrombectomy catheters) improves survival
- Thrombectomy and IIb/IIIa inhibitors may synergistically improve the clinical outcome 14

15. Impact of Thrombus Burden
798 STEMI patients treated with DES
Small Thrombus
Large Thrombus
Final TIMI 3
94.9%
83.6%*
TMPG-3
53.2%
35.4%*
No-reflow
0.5%
4.0%*
Distal embolization
3.5%
17.3%*
P<0.001
risk stent thrombosis
Sianos G. JACC 2007;50:573-83

16. TAPAS Study
Patients have a 5 times higher death rate if left with a Blush Score of 0/1 compared to a Blush Score of 3.
14.1%
% of Pts.
8.8%
5.2%
30 day data
4.2%
2.9% 1%
Svilaas, et al, NEJM, Feb. 2008

17. TAPAS one year outcome: Myocardial blush grade and death at 1 year
P =death/reinfarction a 0.001
Both associations p=0.001
Svilaas T et al. NEJM 2008; FZ
Myocardial blush grade FZ 17 17

18. In Vitro Disaggregation Data
100 X
IV dose
At 100 times the usual systemic IV dose
GP IIb/IIIa inhibitor disaggregates virtually all clot in vitro.
Clear Way delivers close to 600 times systemic concentration
100
10 X
IV dose 90 80 70 60
IV dose 50
Disaggregation Potency (%) 40 30 20 10
µg/ml
0.375 µg/ml
3.76 µg/ml
Moser M, et al. J Cardiovasc Pharmacology 41: , 2003.

19. Bolus only strategy may reduce cost to facility
There was a cost difference, too, with the bolus-only strategy reducing drug costs by more than 50%, from an average of $706 per case to $325 per case. In addition, the GPI bolus-only group had a higher incidence of ambulatory PCI, or same-day discharge after the procedure (13.1% vs. 3.2%, P<0.01), and a reduced length of hospitalization (1.1 days vs days, P<0.01).
Similar results with Epifibitide (Integrilin) Strategy
Kini AS, Chen VHT, Krishnan P, et al. Bolus-only versus bolus + infusion of glycoprotein IIb/IIIa inhibitors during percutaneous coronary intervention. Am Heart J 2008

20. (20% to 54% along treatment zone)
Bolus only ReoPro Infusion with ClearWay RX measured by OCT in NSTEMI- no extraction
COCKTAIL Study A B B A
Area 1.91 mm2
20% Improvement in MLD
(20% to 54% along treatment zone) A B B A
Area 2.30 mm2

21. Change in Lumen Diameter Post ClearWay™ RX Infusion of ReoPro
Pre administration
Area 3.34
Area 3.38
Area 1.91
Area 1.28
Post administration
Area 4.45
Area 4.70
Area 2.30
Area 2.51

22. No residual thrombus post infusion
Final result after stenting
No residual thrombus post infusion

23. COCTAIL Study
Thrombus score change
35,5%
P<0.01
3,7%
RHR
N 19
N 20

24. CRYSTAL AMI- Abciximab administration IC (through ClearWay) vs IV in STEMI

25. Ongoing Coronary ClearWay Clinical Trials
Title:  INFUSE AMI Principal Investigator(s):  Gregg Stone, MD – Columbia Presbyterian (New York, NY) and CO-PI Michael Gibson, MD – Beth Israel Deaconess Medical Center (Boston, MA) Description:  A four-Arm, prospective, randomized, multicenter, single-blind evaluation of intracoronary (IC) Abciximab infusion via ClearWay™ RX and aspiration thrombectomy in patients undergoing percutaneous coronary intervention for anterior ST-segment elevation myocardial infarction (STEMI). Primary Endpoint:  Reduced infarct size at 30 days measured by cardiac MRI
Title:  COCTAIL Study Principal Investigator:  Francesco Prati, MD – Rome Heart Center (Rome, Italy) Description:  A prospective, multi-center study examining the effects of localized intracoronary infusion of abciximab through the ClearWay RX catheter compared to localized infusion through a guide catheter.  Primary Endpoint:  Reduction of thrombus burden measured by OCT
Title:  CRYSTAL MI Principal Investigator:  Rajesh Dave, MD – Harrisburg Hospital (Harrisburg, PA) Description: A randomized, single center, open-label evaluation of local intracoronary (IC) delivery of Abciximab via the ClearWay™ RX catheter versus standard intravenous (IV) delivery of Abciximab in patients with ST-segment elevation MI (STEMI). Primary Endpoints:  Improvement in Myocardial Blush Grade (MBG), ST resolution, and Ejection Fraction
Title: IC ClearLY – Principal Investigators:  Gennaro Sardella, MD, - Policlinico Umberto (Rome, Italy) and Michael Gibson, MD – Beth Israel Deaconess Medical Center (Boston, MA) Description:  A randomized, open-label, multicenter, trial to evaluate the effect of an intracoronary (IC) bolus dose of Abciximab delivered using the ClearWay™RX catheter versus an intravenous (IV) bolus of Abciximab for ST-segment elevation myocardial infarction (STEMI) with angiographically visible thrombus.  Primary Endpoint:  Reduction of infarct size measured by cardiac MRI
Title: ClearWay RX Registry Principal Investigator:  Ron Waksman, MD - Washington Hospital Center (Washington, DC) Description:  The primary goal of this registry is to collect clinical data regarding the use of the ClearWay™ RX Local Therapeutic Infusion Catheter for all coronary indications

26. IC infusion- is it a necessary tool in the lab
May reduce time to reperfusion by targeting thrombus burden at site of lesion in the most efficient manner
May reduce no reflow phenomenon
May address residual thrombus to prevent SAT
May reduce cost with bolus only strategy

27. Intact, Internal Elastic Lamina
How is ClearWay different from other drug delivery balloons of the past?
No barrow trauma
No wire exchange needed
Intact, Internal Elastic Lamina
Virmani