SOLACI in Partnership with TCT: Snapshot of Latin America Practice and Research Room D235-236

Evidence/Practice Intersection: How I Approach Thrombus in My Daily Clinical Practice (and Why)
Ricardo A. Costa Alexandre Abizaid
Instituto Dante Pazzanese de Cardiologia Sao Paulo, Brazil
Monday, October 21st, 2012 From 6:13 to 6:25 pm

DISCLOSURE STATEMENT
I, Ricardo A. Costa DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation

Thrombotic Lesions

Thrombotic Lesions

No-Reflow: A Multifactorial Phenomenon

Vasoconstrictor Thrombotic Mechanical

Serotonin Release

Aggregates of Platelets, Neutrophils, Red Blood Cells Cellular and Intersticial edema

Distal Embolization Spontaneous During reperfusion Tx

Vasoconstriction

Microvascular Occlusion

Mechanical Occlusion

Distal Embolization in STEMI

Distal Embolization occurs in approximately 14% of patients who underwent primary angioplasty
Proximal LCx filling defect at primary PCI site

No DE N=167 (86.1%)
Patency LVEF (%) LDH (Q72) 151 (92) 51 9 847 631

DE N=27 (13.9%)
19 (73) 42 14 1612 1008

P value
0.009 0.005 0.001

Mortality
Death/Re-MI

15 (9)
23.9

12 (44)
21.5

< 0.001
0.48

Distal Thromboemboli Henriques JPS, et al. Eur Heart J. 2002;23:1112-1117

Importance of TIMI-3 Flow

Stone GW, et al. Circulation. 2001;104:636

What is the best therapy to prevent distal embolization?

Pharmacotherapy Distal Protection

Thromboaspiration
New Devices

What is the best therapy to prevent distal embolization?

Pharmacotherapy Distal Protection

Thromboaspiration
New Devices

Impact of Time to Therapy and Reperfusion Modality on the Efficacy of Adenosine in Acute MI: AMISTAD -2 Trial
2118 Patients with Anterior STEMI & Reperfusion Therapy within 6 Hrs of Symptoms
P=0.028
P=NS

Placebo

Adenosine 50 g/Kg/min X 3h

Adenosine 70 g/Kg/min X 3h

26% 23%

57%
11%

Fibrinolysis or PTCA
Infarct size (5 d) (243 patients)

Follow-up for 6 months

Kloner RA et al. Eur Heart J. 2006;27:2400-2405

Abciximab in Primary PCI Meta-Analysis

8 RCTs - 3,949 pts with AMI w/i 12h undergoing primary (7) or rescue (1) PCI random. to abciximab vs. placebo or control

30-Day Events, (%)

p=0.047 OR 0.68 [0.47,0.99]

p=0.03 OR 0.56 [0.33,0.94]

P=0.36 OR 1.16 [0.85,1.59]

4.7% 4.1%

P=0.96 OR 0.97 [0.31,3.01]

3.4% 2.4% 1.9% 1.0% 0.11% 0.06%

De Luca G, et al. JAMA 2005;293:1759-1765

Abciximab in Primary PCI Meta-Analysis

8 RCTs - 3,949 pts with AMI w/i 12h undergoing primary (7) or rescue (1) PCI rand to abciximab vs. placebo or control

Mortality

p=0.047 OR 0.68 [0.47, 0.99]

6.2%

P=0.01 OR 0.69 [0.52, 0.92]

4.4% 3.4% 2.4%

De Luca G, et al. JAMA 2005;293:1759-1765

Intracoronary vs. Intravenous Bolus Abciximab in Pts with STEMI Undergoing Primary PCI
154 pts with STEMI for primary PCI randomized to IC bolus (n=77) or IV bolus (n=77) Abciximab followed by 12-hour infusion

IC Abciximab

IV Abciximab

Primary End-Points
23.4 3.4

%
P=0.006

% of LV

15.1

P=0.02 1.1 P=0.01 0.1 1.1

Assessed by Delayed MRI Thiele H, et al. Circulation. 2008;118:49-57

Intracoronary vs. Intravenous Bolus Abciximab in Pts with STEMI Undergoing Primary PCI

30-Day MACE

P=0.06

Thiele H, et al. Circulation. 2008;118:49-57

What is the best therapy to prevent distal embolization?

Pharmacotherapy Distal Protection

Thromboaspiration
New Devices

Distal Protection Devices

Distal occlusion

Distal Filter

Proximal occlusion/ reverse flow

Distal Microcirculatory Protection During PCI in Acute STEMI - EMERALD Trial

501 pts with AMI < 6h Sx onset, undergoing primary or rescue PCI, rand to: PCI with balloon occlusion and aspiration distal protection (Guardwire Plus; n=252) or PCI without distal protection (n=249)
Rates of Complete (> 70%) STR at Different Time Points

% P=0.40 P=0.14

Stone GW, et al. JAMA 2005;293:1063-1072

Distal Microcirculatory Protection During PCI in Acute STEMI - EMERALD Trial 6-Month Clinical End-Points

16.1

P = NS for all comparisons

%
6.3 5.8 3.4 3.3 3.9 2.4 1.3 2.1 0.4 2.5 0.9 1.7

14.3 11 10

Stone GW, et al. JAMA 2005;293:1063-1072

Randomized Comparison of Distal Protection Versus Conventional Treatment in Primary PCI:

DEDICATION Trial
Distal Protection (Filterwire) (n=302) Conventional PCI (n=301)

5.4

P=NS for all comparisons

3.2 2.6 2.5 1.6 1.9 0.6 1.0 0.6

76

72

%
P=NS

0.3

Conclusion: Distal protection failed to significantly improve ST-segment resolution 90 min. after PCI compared to PCI alone in patients with large STEMI.
Kelbaek H, et al. J Am Coll Cardiol. 2008;51:899-905

What is the best therapy to prevent distal embolization?

Pharmacotherapy Distal Protection

Thromboaspiration
New Devices

X-Sizer for Thrombectomy in AMI Improves ST Segment Resolution: X AMINE ST Trial

201 pts with STEMI < 12h randomized to Thrombectomy (X-Sizer) prior to stent implantation vs. Standard PCI with no thrombectomy Primary End-Point
7.5
P = 0.037
P = NS
96 89

P = NS

P = 0.033 mm
4.9
67.8

52.6

30

31

Predictors of STR > 50% by Multivariate Analysis

Younger Age Non Anterior MI Use of X-Sizer thrombus aspiration device Short time from Symptoms Onset

Lefvre T, et al. J Am Coll Cardiol. 2005;46:246-252

Thrombus Aspiration Before Primary Angioplasty Improves Myocardial Reperfusion in AMI: DEAR-MI
148 consecutive STEMI Pts with Sx < 12h randomized to: PPCI (n=74) or Thrombus Aspiration (Pronto Catheter) before PPCI (n=74) Thrombus Aspiration + PPCI
88% 89% 78% 68% 50%

PPCI
910 128 790 132

44%

P<0.05

P<0.0001

P=NS

P<0.0001

Silva-Orrego P, et al. J Am Coll Cardiol. 2006;48:1552-1559

Thrombus Aspiration During PCI in AMI Study: TAPAS

1071 STEMI pts Thrombus Aspiration (n=535) Thrombus Aspiration (n=530)
1-Year FU

R
Conventional PCI (n=536)

Conventional PCI (n=530)

Primary End-Point: Myocardial Blush Grade

P < 0.001 Patients (%)

Thrombus Aspiration

Conventional PCI

Svillas T, et al. N Engl J Med 2008;358:557-567

Thrombus Aspiration During PCI in AMI Study: TAPAS

ST-Segment Elevation Resolution
P < 0.001

Patients (%)

Thrombus aspiration

Conventional PCI

Svillas T, et al. N Engl J Med 2008;358:557-567

Thrombus Aspiration During PCI in AMI Study: TAPAS

1-Year Mortality
12 10
Conventional PCI Thrombus-Aspiration

Mortality (%)

8 6 4 2 0 0

30 days 4.0% vs. 2.1%, P=0.07

Log-Rank p = 0.040

100

200 Time (days)

300

400

Svillas T, et al. N Engl J Med 2008;358:557-567

Role of Adjunctive Thrombectomy and Embolic Protection Devices in AMI

Meta-Analysis of Randomized Trials
Incidence of Mortality According to the Type of Device Used

5.3% 4.4% 3.1% 3.4%

2.7%

2.8%

Bavry AA, et al. Eur Heart J 2008;29:2989-3001

What is the best therapy to prevent distal embolization?

Pharmacotherapy Distal Protection

Thromboaspiration
New Devices

ClearWayTM Perfusion Balloon

What is ClearWay RX?
Rapid Exchange therapeutic infusion catheter

Basal and FU Thrombus score by OCT

p=0.0015 p= NS

120 100 80 60 40 20 0 Total 101.9 80

105.4 91.2 85.5 68.5

Clearway Inf. Guid. Cath. Inf. Post Abcix.

Basal

MGuard Concept
STENT STENT + EMBOLIC PROTECTION

+
EMBOLIC PROTECTION

MGuard Stent
Bare metal stent (stainless
steel) - Strut width 100 m

Balloon-expandable Protection net (mesh sleeve

fibers of poliethyleneterephthalate)
Fiber width 20 m

Net aperture size (150x180 m)

2.0 4.0mm diameter (every 0.25) 10 38mm length

INSPIRE trial
Brazilian Experience
Register: 30 pts w/ de novo lesions in SVG or native coronaries w/ potential to flow disturbance + 30 pts w/ the same profile

IVUS + QCA Subset analysis Myocardial blush TIMI frame count

Primary Endpoint:

QCA post stent TIMI frame count Myocardial blush

30-day MACE
Secondary endpoints Device success Procedure success 6-12month MACE Late loss

Flow wire
PRE & POST

stent

6-month FU

QCA+ IVUS

In-Hospital Results
50% SVG, 35% of lesions w/ visible thrombus
100 90 80 70 60 50 40 30 20 10 0 TIMI3 flow MBG 3 ck-mb > 3x MACE

CASE # 1

OCLUSO PS IAM

WP

Aspiration

WP

After aspiration

WP

Pre

Final result

PR

PS

CASE # 2

Baseline Angiogram

Strategy

Premedication (ASA + Clop + UFH)

Thrombus aspiration - Export

GP IIb/IIIa Abciximab No predilatation Stent MGuard No postdilatation

 Export AP Aspiration catheter

large thrombus burden

Results post-aspiration

 MGuardstent 3.0 x 15 mm

Results post stent

CASE # 3

Baseline Angiogram

Baseline Angiogram

Strategy
Premedication (ASA + Clopidogrel)
Anti-thrombin with Enoxaparin for 7 days Repeat coronary angiography and PCI to SVG

7 DAYS AFTER

 MGuard stent 3.5 x 29 mm

Results post stent

Conclusions / Recomendations
Pharmacotherapy:
IC injection of Abciximab and Adenosine

Distal Protection:
No significant advantages in acute MI

Thromboaspiration:
Most cases significant improvement

New Devices: promising data