A Prospective Randomized Trial of Proximal
Microcirculatory Protection in Patients with
Acute Myocardial Infarction Undergoing
Primary PCI
The PREPARE Trial
PRoximal Embolic Protection in Acute MI and Resolution of ST-Elevation
Karel T. Koch
Joost D.E. Haeck, Jan G.P. Tijssen, Luc Bilodeau*, René J. van der Schaaf,
José P.S. Henriques, Allard van der Wal, Jan Baan Jr., Marije M. Vis, Jan J. Piek,
Mitchell W. Krucoff†, Robbert J. de Winter.
Academic Medical Center - University of Amsterdam, The Netherlands
*Institut de Cardiologie de Montréal, QC, Canada
†Duke Clinical Research Institute, Duke University Medical Center, Durham, NC, USA
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
Disclosure statement of financial interest
Within the past 12 months, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
Company
Grant/Research Support:
Educational Grant
Academic Medical Center Amsterdam
Interventional Cardiology
St. Jude Medical
Koch TCT 2008
Background
Inadequate myocardial reperfusion relates to prognosis,
even in the presence of adequate epicardial flow.
Embolization of atherothrombotic material plays a crucial
role in microvascular obstruction and impaired
myocardial perfusion.
The Proxis™ device is a combined system of proximal
embolic protection and thrombus aspiration. The device
has been shown feasible and safe in primary PCI*.
The PREPARE Trial was designed to evaluate primary PCI
with the Proxis system compared to primary PCI alone.
*Koch KT et al. Rev Cardiovasc Med. 2007;8(3): 160-6
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
Proxis embolic protection system
Full length flexible catheter
6F and 7F GC compatible
Sealing balloon at the tip
CO2 based inflation device
Deployed proximal to target
lesion before crossing
Inflation of balloon suspends
antegrade flow during lesion
intervention
Stagnated blood and emboli
liberated during intervention
are retrieved by gentle
aspiration
Academic Medical Center Amsterdam
Interventional Cardiology
Proxis™ embolic protection system (St. Jude Medical, St. Paul, MN, USA)
Koch TCT 2008
PREPARE Trial
• PRoximal Embolic Protection in Acute MI and
Resolution of ST-Elevation
• Investigator-initiated randomized trial
• Comparison of primary PCI with Proxis system
versus primary PCI alone
• Open trial with blinded evaluation of end points
• Participation of 2 centers
• 140 patients in each study arm
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
Patient selection
Inclusion criteria
• Consecutive STEMI patients ≤ 6 h
• ST-segment elevation ≥ 2 mm in ≥ 2 leads
• TIMI flow grade 0 to 1 at first angiogram
• Coronary anatomy suitable for Proxis
• ECG suitable for ST-segment resolution
evaluation
Exclusion criteria
• Recurrence of MI in same area
• Prior CABG or lytics
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
PREPARE Trial
Study flow chart
UFH 70 U/kg
ASA 300 mg
Clopidogrel 600 mg
STEMI ≤ 6 h
Continuous
ST Holter
Coronary angiogram
R
24 h
Primary PCI
with Proxis
Primary PCI
alone
Clinical follow up at 30 days
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
End points
Primary end point
• ST-segment elevation resolution (STR) over time*
Secondary end points
• TIMI graded flow
• Myocardial blush grade
• Angiographic signs of distal embolization
• Composite of death, MI, TVR, and stroke at 30 days
*Duke Clinical Research Institute Core Lab
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
Patient characteristics
Proxis
Control
n = 141
n = 143
62 ± 11
59 ± 11
Male
80%
80%
Family history CAD
35%
38%
Hypercholesterolemia
21%
13%
Current smoking
50%
65%
Hypertension
31%
23%
Diabetes
12%
6%
6%
9%
33%
31%
170
153
Age
Previous MI
Multivessel disease
Symptoms to balloon (min)
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
Lesion characteristics
Proxis
Control
n = 141
n = 143
Infarct related artery
RCA
LAD
LCx
61%
29%
10%
60%
29%
11%
0
1
90%
9%
89%
8%
2
1%
4%
Pre-PCI TIMI graded flow
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
Procedural characteristics
Proxis
Control
n = 141
n = 143
Procedural success
100%
Proxis placed
94%
Predilatation and stenting
87%
Direct stenting
11%
Balloon angioplasty
3%
GP IIb/IIIa receptor antagonists
43%
Additional thrombus aspiration
6%
Pathology confirmed thrombus
75%
Puncture to balloon (min)
Median
17
IQR
13-23
99%
─
76%
19%
6%
35%
6%
─
*
14*
10-18
*P<0.05; IQR interquartile range
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
Complete (>70%) STR
*Primary endpoint
Academic Medical Center Amsterdam
Interventional Cardiology
Proxis
Control
n = 141
n = 143
P-value
(Fisher’s Exact Test)
Koch TCT 2008
Complete (>70%) STR
Immediate
*Primary endpoint
Academic Medical Center Amsterdam
Interventional Cardiology
Proxis
Control
n = 141
n = 143
66%
(85/129)
50%
(67/135)
P-value
0.009
(Fisher’s Exact Test)
Koch TCT 2008
Complete (>70%) STR
Proxis
Control
n = 141
n = 143
P-value
Immediate
66%
(85/129)
50%
(67/135)
0.009
30 min
75%
(91/122)
66%
(86/130)
0.17
60 min
80% (101/126)
72%
(93/129)
0.14
90 min
81% (100/124)
74%
(97/131)
0.23
120 min
78%
76% (100/131)
0.88
(98/126)
(Fisher’s Exact Test)
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
Complete STR over time
90
P=0.009
Patients with complete STR, %
80
70
Proxis
60
Control
50
40
Last
contrast
Academic Medical Center Amsterdam
Interventional Cardiology
30
60
90
120
Time after last contrast, min
Koch TCT 2008
Mean % STR
Proxis
Control
n = 141
n = 143
P-value*
Immediate
73 ± 27
63 ± 32
0.009
30 min
79 ± 21
75 ± 23
0.30
60 min
82 ± 20
78 ± 21
0.27
90 min
82 ± 19
80 ± 21
0.17
120 min
82 ± 19
81 ± 20
0.48
Mean (SD); *T-Test
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
Angiographic parameters
Proxis
Control
n = 141
n = 143
P-value
Post-PCI TIMI graded flow
3
93%
2
7%
0-1
0%
87%
11%
2%
0.06*
Myocardial blush grade
3
2
0-1
81%
16%
4%
83%
11%
6%
0.93*
Distal embolization (yes/no) 10%
14%
0.36†
*Cochran-Armitage Test
†Fisher’s Exact Test
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
Clinical events at 30 days
Proxis
Control
n = 141
n = 143
Death
2
2
MI
2
3
TVR
3
6
Stroke
0
1
MACCE*
6 (4%)
10 (7%)
no complications at Proxis landing zone
*ARC MACCE definition Circ. 2007; 115: 2344–2351
Academic Medical Center Amsterdam
Interventional Cardiology
For descriptive purposes only; no statistical comparisons done
Koch TCT 2008
In conclusion
The Proxis system is feasible and safe in the setting of STEMI,
and effectively retrieves embolic debris in most patients.
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
In conclusion
The Proxis system is feasible and safe in the setting of STEMI,
and effectively retrieves embolic debris in most patients.
Complete STR was better in Proxis treated patients compared
to control patients. The difference in STR immediately after PCI
was highly statistically significant (p=0.009).
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
In conclusion
The Proxis system is feasible and safe in the setting of STEMI,
and effectively retrieves embolic debris in most patients.
Complete STR was better in Proxis treated patients compared
to control patients. The difference in STR immediately after PCI
was highly statistically significant (p=0.009).
The results of the PREPARE trial suggest that primary PCI with
combined proximal embolic protection and aspiration leads to
better immediate microvascular flow in STEMI patients.
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008
PREPARE Trial
PRoximal Embolic Protection in Acute MI and Resolution of ST-Elevation
Thank you for your attention
[email protected]
Academic Medical Center Amsterdam
Interventional Cardiology
Koch TCT 2008