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STEMI in the Cath Lab
• primary PCI • primary PCI
Role of PCI in the management of STEMIRole of PCI in the management of STEMIagendaagenda
• the challenges• the challengeshow to achieve optimal reperfusionhow to achieve optimal reperfusionwhat to do with the occluded IRAwhat to do with the occluded IRAreplacing the function of death cellsreplacing the function of death cells
- angioplasty vs thrombolysis- angioplasty vs thrombolysis
- added benefit of stent placement- added benefit of stent placement- timing
- culprit vessel vs all vessel intervention
- role of 2b/3a inhibitors
- timing
- culprit vessel vs all vessel intervention
- role of 2b/3a inhibitors
• transfer, rescue and facilitated PCI• transfer, rescue and facilitated PCI
• primary PCI • primary PCI
Primary PCI
angioplasty vs thrombolysisangioplasty vs thrombolysis
primary PTCA vs thrombolysis randomized trials
primary PTCA vs thrombolysis randomized trials
Zijlstra 1Zijlstra 2RibeiroGrinfeld De WoodGrinesGibbonsRibichini Garcia GUSTO 2b
Zijlstra 1Zijlstra 2RibeiroGrinfeld De WoodGrinesGibbonsRibichini Garcia GUSTO 2b
29495
100112
90395103
83189
1138
29495
100112
90395103
83189
1138totaltotal 25992599
primary PTCA vs lysis in AMIprimary PTCA vs lysis in AMI
PTCAn 1290PTCAn 1290
death
reMI
death/ reMI
total stroke
ICH
death
reMI
death/ reMI
total stroke
ICH
4.4%
2.9%
7.2%
0.7%
0.1%
4.4%
2.9%
7.2%
0.7%
0.1%
6.5%
5.3%
11.9%
2.0%
1.1%
6.5%
5.3%
11.9%
2.0%
1.1%
lysisn 1316lysis
n 1316
00 0.50.5 1.51.511 22
odds ratio (95% CI)odds ratio (95% CI)
PTCAbetterPTCAbetter
lysisbetterlysis
better
0.66 (0.46-0.94)0.66 (0.46-0.94)
0.53 (0.34-0.80)0.53 (0.34-0.80)
0.58 (0.44-0.76)0.58 (0.44-0.76)
0.35 (0.14-0.77)0.35 (0.14-0.77)
0.07 (0.00-0.43)0.07 (0.00-0.43)
30-day outcomes30-day outcomes
WD Weaver JAMA 1997; 278: 2093-8WD Weaver JAMA 1997; 278: 2093-8
deathdeath 4.4%4.4% 6.5%6.5%
PTCA vs lysis30 day death/reMI, subgroup analysis
PTCA vs lysis30 day death/reMI, subgroup analysis
age <6060-70>70
age <6060-70>70
PTCAPTCA
0.10.1 0.20.2 110.50.5 22
OR (95% CI)OR (95% CI)lysislysis
DM yesno
DM yesno
MI anteriornon-anterior
MI anteriornon-anterior
prior MI yesno
prior MI yesno
4.3%4.3%6.3%6.3%
13.3%13.3%9.2%9.2%6.5%6.5%8.2%8.2%6.2%6.2%9.7%9.7%6.6%6.6%
8.2%8.2%12.8%12.8%23.6%23.6%19.3%19.3%11.8%11.8%14.5%14.5%12.0%12.0%22.7%22.7%11.5%11.5%
PTCA betterPTCA better lysis betterlysis better
risk group low interm. high
risk group low interm. high
2.9%8.0%
13.1%
2.9%8.0%
13.1%
7.2%12.7%24.1%
7.2%12.7%24.1%
23231515
881010161613131616
8877
27271515
88
NNTNNT
source: PCAT collaborators AHJ 2003;145:47-57source: PCAT collaborators AHJ 2003;145:47-57
primary PTCA vs lysisprimary PTCA vs lysis6-month outcomes: death/reMI6-month outcomes: death/reMI
00 0.50.5 1.51.511 22
odds ratio (95% CI)odds ratio (95% CI)PTCAPTCA
death
reMI
death/ reMI
death
reMI
death/ reMI
lysislysis
PTCA betterPTCA better lysis betterlysis better
0.73(0.55-0.98)0.73(0.55-0.98)
0.46(0.34-0.64)0.46(0.34-0.64)
0.63(0.50-0.78)0.63(0.50-0.78)
source: PCAT collaborators AHJ 2003;145:47-57source: PCAT collaborators AHJ 2003;145:47-57
6.2%
4.8%
10.3%
6.2%
4.8%
10.3%
8.2%
9.8%
16.3%
8.2%
9.8%
16.3%death/ reMIdeath/ reMI 10.3%10.3% 16.3%16.3%
primary PCI vs lysisprimary PCI vs lysis
PTCAPTCA
lysislysis
p = 0.002p = 0.002
deathdeath
p <0.001p <0.001
reMIreMI
p < 0.0001p < 0.0001
death/reMI/strokedeath/reMI/stroke00
55
1010
1515
2020%
patients%
patients
EC KEELEY. JAMA 2003;361:13-20EC KEELEY. JAMA 2003;361:13-20
long-term (6-18 m) outcomes23 CRT (7739 pts)
long-term (6-18 m) outcomes23 CRT (7739 pts)
Primary PCI
POBA vs StentPOBA vs Stent
primary PTCA vs stent randomized trials
primary PTCA vs stent randomized trials
FRESCOZWOLLEGRAMIPAMIPASTASTENTIM-2CADILLACPSAAMI
FRESCOZWOLLEGRAMIPAMIPASTASTENTIM-2CADILLACPSAAMI
150 227 104 900 136 211
1028 88
150 227 104 900 136 211
1028 88
total total 28442844
primary PTCA vs stentprimary PTCA vs stent6-month outcomes6-month outcomes
00 0.50.5 1.51.511 22
OR (95% CI)OR (95% CI)stentstent
death
reMI
death/ reMI
TVR
death/reMI/TVR
death
reMI
death/ reMI
TVR
death/reMI/TVR
3.3%
1.7%
4.9%
8.3%
13.7%
3.3%
1.7%
4.9%
8.3%
13.7%
3.8%
3.0%
6.8%
18%
25.9%
3.8%
3.0%
6.8%
18%
25.9%
PTCAPTCA
stent betterstent better PTCA betterPTCA better
0.85 (0.57-1.27)0.85 (0.57-1.27)
0.58 (0.35-0.96)0.58 (0.35-0.96)
0.72 (0.52-0.98)0.72 (0.52-0.98)
0.41 (0.32-0.52)0.41 (0.32-0.52)
0.45 (0.37-0.55)0.45 (0.37-0.55)
death/ reMIdeath/ reMI 4.9%4.9% 6.8%6.8%
number of events (death / reMI) prevented at 6-month F/U x 1000 patients treated
number of events (death / reMI) prevented at 6-month F/U x 1000 patients treated
thrombolysisthrombolysis
6060
POBAPOBA
1919 stentingstenting
POBAPOBAvsvs
stentingstentingvsvs
STAT study JACC 2001;37:985-91
STAT study JACC 2001;37:985-91
7474
Is timing an issue even for Primary PCI?
Survival Benefit by Time to Treatment with Lytics
Mortality by time to reperfusion with Primary PCINRMI-2 Registry (27,080)
C.P. CANNON. JAMA 2000;283:2941-7
Why is Primary PCI less time dependent than Lysis?
1) Lysis is less effective at restoring infarct artery patency as the clot ages
Why is Primary PCI less time dependent than Lysis?
1) Lysis is less effective at restoring infarct artery patency as the clot ages
2) Myocardial salvage and infarct size after lytics are very sensitive to time to reperfusion
Why is Primary PCI less time dependent than Lysis?
1) Lysis is less effective at restoring infarct artery patency as the clot ages
2) Myocardial salvage and infarct size after lytics are very sensitive to time to reperfusion
3) Cardiac rupture is more likely to occur as the time to lysis increases
Recommendations
• When performed by experienced* operators/centers, PCI is the reperfusion strategy of choice for patients with AMI
• PCI for AMI: door-to-balloon time < 2hrs (time window up to 12 hours accepted)
* operator: 75 PCI (any type) / year; center: 36 Primary PCI / year
After 12 hours???BRAVE-2Rationale: While thrombolysis has been shown to produce no benefit after 12 hours, no similar studies have looked at primary PCI in this group.
Study: 365 patients randomized to in an invasive arm or a conservative arm. The invasive group underwent angiography and then PCI if necessary, while the conservative group was treated with conventional medical therapy. The primary end point was infarct size determined by SPECT at five to 10 days.
Results: Infarct size (%LV) was significantly reduced in the invasive arm (8.0 vs 13%; p=0.002). No clinical differences.
Kastrati ACC 2005
• primary PCI • primary PCI
Role of PCI in the management of STEMIRole of PCI in the management of STEMIagendaagenda
• the challenges• the challengeshow to achieve optimal reperfusionhow to achieve optimal reperfusionwhat to do with the occluded IRAwhat to do with the occluded IRAreplacing the function of death cellsreplacing the function of death cells
- angioplasty vs thrombolysis- angioplasty vs thrombolysis
- added benefit of stent placement- added benefit of stent placement- timing
- culprit vessel vs all vessel intervention
- role of 2b/3a inhibitors
- timing
- culprit vessel vs all vessel intervention
- role of 2b/3a inhibitors
• transfer, rescue and facilitated PCI• transfer, rescue and facilitated PCI
• primary PCI • primary PCI
culprit vessel vs all vessel intervention
• The ACC/AHA guidelines on PCI give elective PCI of a non-infarct related artery at the time of AMI a class III recommendation with a C level of evidence.
• Exception: in case of cardiogenic shock, systematic intervention in multiple vessels may be required to optimize reperfusion of the heart.
Role of GP 2b/3a inhibitors
26.1%26.1%
11.2%11.2%9.7%9.7%
14.6%14.6%
4.5%4.5% 5.8%5.8%2.0%2.0%
6.0%6.0%
0%0%
10%10%
20%20%
30%30%
EPICEPIC RAPPORTRAPPORT NeumannNeumann ADMIRALADMIRAL
PlaceboPlacebo GP IIb/IIIaGP IIb/IIIa
p = 0.06p = 0.06 p = 0.03p = 0.03 p = 0.03p = 0.03 p = 0.01p = 0.01
N: 64 483 200 300 2082 N: 64 483 200 300 2082
GP IIb/IIIa Inhibitors For Primary PCI—30-Day Death, (re)MI or Urgent Revascularization
GP IIb/IIIa Inhibitors For Primary PCI—30-Day Death, (re)MI or Urgent Revascularization
6.8%6.8%4.5%4.5%
CADILLACCADILLAC
p = 0.02p = 0.02
the ADMIRAL studythe ADMIRAL study
61615858
6464
5757
6161
5757
abcixabcix
G. MONTALESCOT. NEJM 2001;344:1895-903G. MONTALESCOT. NEJM 2001;344:1895-903
LV function at 24hLV function at 24h
00
2020
4040
6060
8080
EF (%)EF (%)
placeboplacebooveralloverall
abcixabcix placeboplaceboCCU/cath labCCU/cath lab
abcixabcix placeboplaceboMICU/ERMICU/ER
p<0.05p<0.05 NSNS p<0.05p<0.05
Eptifibatide
Cutlip DE et al. Am J Cardiol 2001; 88: 62-4
Tirofiban
Lee DP et al. Circulation 2003; 107: 1497-501
Other 2b/3a inhibitors
• primary PCI • primary PCI
Role of PCI in the management of STEMIRole of PCI in the management of STEMIagendaagenda
• the challenges• the challengeshow to achieve optimal reperfusionhow to achieve optimal reperfusionwhat to do with the occluded IRAwhat to do with the occluded IRAreplacing the function of death cellsreplacing the function of death cells
- angioplasty vs thrombolysis- angioplasty vs thrombolysis
- added benefit of stent placement- added benefit of stent placement- timing
- culprit vessel vs all vessel intervention
- role of 2b/3a inhibitors
- timing
- culprit vessel vs all vessel intervention
- role of 2b/3a inhibitors
• transfer, rescue and facilitated PCI• transfer, rescue and facilitated PCI
door-to-balloon times in primary PCIdoor-to-balloon times in primary PCI
8%8%
21% 21%24%24%
17%17%
10%10%
20%20%
<60<60 60-9060-90 120-150120-15090-12090-120 150-180150-180 >180>18000
55
1010
1515
2020
% of patients% of patients
minminC.P. CANNON. JAMA 2000;283:2941-7C.P. CANNON. JAMA 2000;283:2941-7
NRMI-2 : 27080 consecutive patientsNRMI-2 : 27080 consecutive patients
When patients present to a primary unit without interventional capabilities:Therapeutic options
a) lyticsb) “transfer” to a facility with a cardiac
cath lab (with or without adjunctive therapy – “facilitated PCI”).
Any such “transfer” needs to be effected rapidly to take advantage of the early benefits of revascularization.
MAASTRICHT
PRAGUE 1
DANAMI 2
PRAGUE 2
AIR PAMI
MAASTRICHT
PRAGUE 1
DANAMI 2
PRAGUE 2
AIR PAMI
thrombolysis vs transfer & primary PCIthrombolysis vs transfer & primary PCIrandomized trialsrandomized trials
n
150
200
1572
850
138
total 2910
n
150
200
1572
850
138
total 2910
MAASTRICHT
PRAGUE 1
DANAMI 2
PRAGUE 2
AIR PAMI
MAASTRICHT
PRAGUE 1
DANAMI 2
PRAGUE 2
AIR PAMI
n
150
200
1572
850
138
n
150
200
1572
850
138
lysis
6.7%
14.0%
7.6%
10.0%
12.1%
lysis
6.7%
14.0%
7.6%
10.0%
12.1%
PCI
6.7%
7.0%
6.6%
6.8%
8.4%
PCI
6.7%
7.0%
6.6%
6.8%
8.4%
0.00.0 0.50.5 1.51.511 2.02.0
OR 95% CIOR 95% CI
lysis better lysis better PCI betterPCI better
1.0(0.28-3.61)1.0(0.28-3.61)1.0(0.28-3.61)1.0(0.28-3.61)
0.45(0.17-1.17)0.45(0.17-1.17)0.45(0.17-1.17)0.45(0.17-1.17)
0.86(0.59-1.27)0.86(0.59-1.27)0.86(0.59-1.27)0.86(0.59-1.27)
0.65(0.40-1.07)0.65(0.40-1.07)0.65(0.40-1.07)0.65(0.40-1.07)
0.68(0.22-2.08)0.68(0.22-2.08)0.68(0.22-2.08)0.68(0.22-2.08)
30-day mortality30-day mortalitythrombolysis vs transfer & primary PCIthrombolysis vs transfer & primary PCI
0.74(0.57-0.98)0.74(0.57-0.98)0.74(0.57-0.98)0.74(0.57-0.98)p=0.03p=0.038.8%8.8% 6.7% 6.7% 29102910pooledpooled
thrombolysis vs transfer & primary PCIthrombolysis vs transfer & primary PCI
† from admission† from admission
minmin
5050
100100
150150
200200
00MAASTRICHTMAASTRICHT DANAMI 2DANAMI 2 PRAGUE 2PRAGUE 2PRAGUE 1PRAGUE 1 AIR PAMI †AIR PAMI †
thrombolysisthrombolysis
8585
1010
4949
1212
5151
t to treatment (from randomization)t to treatment (from randomization)
PCIPCI
1001008080 9999 9494
155155
thrombolysis vs transfer & primary PCIthrombolysis vs transfer & primary PCI
00
5050
100100
150150minmin
pooledpooled
thrombolysisthrombolysis
PCIPCI
41
106106
57
9090
10 CRT’s10 CRT’s
6565 3333
If transfer PCI is considered:
Recommended time to arrival < 2 hours
(directly to cath lab – bypass ER)
If thrombolytic therapy is considered, but no signs of reperfusion: transfer for rescue PCI
ISAM, INJECT, HIT 4 data (3912 patients)ISAM, INJECT, HIT 4 data (3912 patients)
partial(30- 70%)
partial(30- 70%)
absent(<30%)absent(<30%)
2.7%2.7%4.7%4.7%
13.5%13.5%
complete(>70%)
complete(>70%)
00
55
1010
1515
death %death %
ST segresolutionST segresolution
30-day mortality by ST segment resolution at 180 min
30-day mortality by ST segment resolution at 180 min
Belenkie
RESCUE
PRAGUE
Vermeer
Belenkie
RESCUE
PRAGUE
Vermeer
rescue PCI in acute MI randomized trials
rescue PCI in acute MI randomized trials
28
151
200
149
28
151
200
149
totaltotal 528528
rescue PCIshort term outcome: death
rescue PCIshort term outcome: death
Belenkie
RESCUE
PRAGUE
Vermeer
Belenkie
RESCUE
PRAGUE
Vermeer
n PCI cons.n PCI cons.
28
151
200
149
28
151
200
149
6.3%
5.1%
7%
8.7%
6.3%
5.1%
7%
8.7%
33.3%
9.6%
14.0%
6.7%
33.3%
9.6%
14.0%
6.7%
00 0.50.5 1.51.511 2.02.0
odds ratio (95% CI)odds ratio (95% CI)
0.13 (0.01-1.40)0.13 (0.01-1.40)
0.51 (0.12-2.06)0.51 (0.12-2.06)
0.46 (0.16-1.30)0.46 (0.16-1.30)
1.24 (0.31-4.49)1.24 (0.31-4.49)
0.55 (0.30-1.01)0.55 (0.30-1.01) p=0.052p=0.052totaltotal 528528 6.7%6.7% 11.5%11.5%
2.5%
4.9%
0%
5%
10%
15%
20%
2.5%
4.9%
0%
5%
10%
15%
20%
Pre HospitalLysis
Pre HospitalLysis
PrimaryPCI
PrimaryPCI
P=0.09P=0.09Incidence of ShockIncidence of Shock
CAPTIM – Prehospital tPA vs 1°PCI1 Year ResultsCAPTIM – Prehospital tPA vs 1°PCI1 Year Results
Bonnefoy Lancet 2002Bonnefoy Lancet 2002
5.4%
7.3%
0%
10%
5.4%
7.3%
0%
10% P=0.27P=0.27
Death at 1 YearDeath at 1 Year
Pre HospitalLysis
Pre HospitalLysis
PrimaryPCI
PrimaryPCI
Studies of early angioplasty after thrombolytics
GRACIA I
Facilitated PCI• Use of pharmacological treatment to establish
early reperfusion before catheterization. This strategy combines the benefits of early revascularization with easier intervention (since the artery will already be open in many patients). Facilitation may be obtained with full dose GP 2b/3a inhibitors, full dose lytics, or a combination of half dose lytics + full dose GP 2b/3a inhibitors.
- While primary PCI appears superior to thrombolysis in direct
comparison studies, few patients have prompt access to the cath.
lab.
- While primary PCI appears superior to thrombolysis in direct
comparison studies, few patients have prompt access to the cath.
lab.
rationalerationale
- treatment delays are common and likely reduce the true benefit
of PCI
- treatment delays are common and likely reduce the true benefit
of PCI
- TIMI 3 grade flow prior to PCI is a determinant of success rate and
clinical outcomes
- TIMI 3 grade flow prior to PCI is a determinant of success rate and
clinical outcomes
Effect of Pre-procedural TIMI Flow on Cumulative Late Mortality after Primary PTCA
100%100%
98%98%
96%96%
94%94%
92%92%
90%90%00 11 22 33 44 55 6 6
0.5%0.5%
2.8%2.8%4.4%4.4%
log-rank log-rank P P for trend = 0.009for trend = 0.009
Grade 3Grade 3Grade 2Grade 2Grade 1Grade 1
MonthsMonths
N = 2,507 pts in PAMI-1, PAMI-2, PAMI Stent Pilot, PAMI Stent N = 2,507 pts in PAMI-1, PAMI-2, PAMI Stent Pilot, PAMI Stent N = 2,507 pts in PAMI-1, PAMI-2, PAMI Stent Pilot, PAMI Stent N = 2,507 pts in PAMI-1, PAMI-2, PAMI Stent Pilot, PAMI Stent
Su
rviv
al (
%)
Su
rviv
al (
%)
Stone Circ 2001Stone Circ 2001Stone Circ 2001Stone Circ 2001
6-Month 6-Month MortalityMortality
multivariate predictors of deathmultivariate predictors of death
age (continuous)
anterior MI
female gender
3-vessel disease
pre-PCI TIMI 0-2 flow
age (continuous)
anterior MI
female gender
3-vessel disease
pre-PCI TIMI 0-2 flow
OR (95% CI)
1.06 (1.02-1.10)
4.6 (2.1-10.0)
3.3 (1.6-6.7)
2.5 (1.2-5.6)
2.1 (1.2-37)
OR (95% CI)
1.06 (1.02-1.10)
4.6 (2.1-10.0)
3.3 (1.6-6.7)
2.5 (1.2-5.6)
2.1 (1.2-37)
p
0.001
0.001
0.008
0.01
0.04
p
0.001
0.001
0.008
0.01
0.04
GW STONE. Circulation 2001; 104:636-41GW STONE. Circulation 2001; 104:636-41
pre-PCI TIMI 0-2 flowpre-PCI TIMI 0-2 flow 2.1 (1.2-37)2.1 (1.2-37) 0.040.04
TIMI 0 Complete occlusion
TIMI 1 Penetration of obstruction by contrast but no distal perfusion
TIMI 2 Perfusion of entire artery
but delayed flow
TIMI 3 Full perfusion, normal flow
10.6
7
4.7
0
2
4
6
8
10
12
14
TIMI 0/1 TIMI 2 TIMI 3
Mortality at 42 Days
P < 0.005
TIMI 1TIMI 1
OPEN ARTERY THEORY:Better flow in the infarct artery improves survival
Chesebro JH et al. Circulation 1987;76:142-54
66667272
5454 56564747
404043433939
00
1010
2020
3030
4040
5050
6060
7070
8080 Full-Dose LyticFull-Dose Lytic
GP IIb/IIIa +LyticGP IIb/IIIa +Lytic
% T
IMI 3
Flo
w (
60-9
0 m
ins
)%
TIM
I 3 F
low
(60
-90
min
s)
% T
IMI 3
Flo
w (
60-9
0 m
ins
)%
TIM
I 3 F
low
(60
-90
min
s)
IMPACT-AMIIMPACT-AMI TIMI-14 SPEED TIMI-14 SPEED INTRO-AMI INTRO-AMIFull-Dose t-PA +Full-Dose t-PA + t-PA + r-PA + t-PA + t-PA + r-PA + t-PA + Eptifibatide Abciximab Abciximab EptifibatideEptifibatide Abciximab Abciximab Eptifibatide
IMPACT-AMIIMPACT-AMI TIMI-14 SPEED TIMI-14 SPEED INTRO-AMI INTRO-AMIFull-Dose t-PA +Full-Dose t-PA + t-PA + r-PA + t-PA + t-PA + r-PA + t-PA + Eptifibatide Abciximab Abciximab EptifibatideEptifibatide Abciximab Abciximab Eptifibatide
Early TIMI 3 Flow with Combination TherapyEarly TIMI 3 Flow with Combination Therapy
Facilitated angioplasty studies
Half-Dose t-PA Before PCI: PACT Trial (n=606)Half-Dose t-PA Before PCI: PACT Trial (n=606)
1533
19
28
0
20
40
60
80
100
Placebo 50 mg t-PA
TIMI 2
TIMI 3
1533
19
28
0
20
40
60
80
100
Placebo 50 mg t-PA
TIMI 2
TIMI 361*
34
% P
atie
nts
Ross JACC 1999Ross JACC 1999Ross JACC 1999Ross JACC 1999
*
*
*p < 0.001 vs placebo
LVEF 58.4% 58.2%Rec Ischemia 13.5% 17.9%Reocclusion 3.7% 5.9%Major Bleed 13.5% 12.9%Death at 30d 3.3% 3.6%
P = NS
Full-Dose TNK 3-12h Before PCI: GRACIA-2Full-Dose TNK 3-12h Before PCI: GRACIA-2
Characteristic TNK+PCI PCI
No. patients 103 102
TIMI flow grade 3 59%* 43%
Complete STRes (6h) 61%* 43%
Death, MI, RI-UR 9% 12%
Major bleeding 2% 3%
No differences in infarct size, LV function
*p < 0.05
Characteristic TNK+PCI PCI
No. patients 103 102
TIMI flow grade 3 59%* 43%
Complete STRes (6h) 61%* 43%
Death, MI, RI-UR 9% 12%
Major bleeding 2% 3%
No differences in infarct size, LV function
*p < 0.05
Aviles ESC 2003Aviles ESC 2003Aviles ESC 2003Aviles ESC 2003
facilitated PCI facilitated PCI randomized trialsrandomized trials
nn
6000
4000
1900
4000
200
507
100
6000
6000
4000
1900
4000
200
507
100
6000
ADVANCED- MI
ASSENT PCI
CARESS
FINESSE
GRACIA 2
ON-TIME
TIGER-PILOT
TIGER
ADVANCED- MI
ASSENT PCI
CARESS
FINESSE
GRACIA 2
ON-TIME
TIGER-PILOT
TIGER
studystudy
½ TNK+eptif/early eptif
TNK+enox/adj. GPIIb/IIIa
½ rPA+abcix•/ ½rPA+abcix
½rPA + abcix/early abcix/adj.abcix
TNK+enox/adj.abcix
pre-hosp tirofiban/cath lab tirofiban
ER tirofiban/cath lab tirofiban
½TNK+tirofiban•/ ½TNK+tirofiban
½ TNK+eptif/early eptif
TNK+enox/adj. GPIIb/IIIa
½ rPA+abcix•/ ½rPA+abcix
½rPA + abcix/early abcix/adj.abcix
TNK+enox/adj.abcix
pre-hosp tirofiban/cath lab tirofiban
ER tirofiban/cath lab tirofiban
½TNK+tirofiban•/ ½TNK+tirofiban
treatmentstreatments
• PCI to be performed only in case of no ST-segment resolution• PCI to be performed only in case of no ST-segment resolution
Main Results of ADVANCE-MIMain Results of ADVANCE-MI
2.6
10.1 10
25
0
5
10
15
20
25
Death orSevere CHF
MajorHemorrhage
Placebo +eptifibatide
1/2 TNK +eptifibatide
Giugliano AHA 2004
P = 0.09
P = 0.02
Trial stopped after 149 patients randomized !
• how to achieve optimal reperfusion
• what to do with the IRA found to be
occluded (on late angiography)
• the replacement of function of death cells
• how to achieve optimal reperfusion
• what to do with the IRA found to be
occluded (on late angiography)
• the replacement of function of death cells
current challengescurrent challenges
• how to achieve optimal reperfusion• how to achieve optimal reperfusionpatency (TIMI 2,3) reperfusion (cTFC/MBG)patency (TIMI 2,3) reperfusion (cTFC/MBG)
survival (%) survival (%)
follow up (days)follow up (days)
00
8080
9090
100100
400400 600600 800800
survival in TIMI 3 flow patientssurvival in TIMI 3 flow patients
12001200 14001400
JPS HENRIQUES. Circulation 2003;107:2115-9JPS HENRIQUES. Circulation 2003;107:2115-9
200200
MBG 2/3 n 823
MBG 2/3 n 823
10001000
MBG 0/1 n 101
MBG 0/1 n 101
*p<0.001*p<0.001
*log rank:20.55, p>0.001*log rank:20.55, p>0.001
mechanism/s of impaired blood flowmechanism/s of impaired blood flow• vasoconstriction / vasospasm
• loss of capillary autoregulation
• microvascular plugging
vasoconstriction of microvascular vessels linked to
platelet/leucocyte aggregates, inflammatory cytokines,
endothelial dysfunction
• distal embolization of angiographically visible vessels
• tissue oedema
• vasoconstriction / vasospasm
• loss of capillary autoregulation
• microvascular plugging
vasoconstriction of microvascular vessels linked to
platelet/leucocyte aggregates, inflammatory cytokines,
endothelial dysfunction
• distal embolization of angiographically visible vessels
• tissue oedema
• pharmacologic agents
• direct stenting
• endovascular cooling
• distal protection devices
• pharmacologic agents
• direct stenting
• endovascular cooling
• distal protection devices
optimal reperfusionoptimal reperfusion
CRT’s of agents designed to improve tissue reperfusion
CRT’s of agents designed to improve tissue reperfusion
resultresult
-----++-----
-----++-----
agentagent
metoprololprostacyclin
fluosolmagnesiumrheoth RxabciximabadenosineHu 23F2G
glucose/insulin/KAMP 579
pexelizumabpexelizumab
metoprololprostacyclin
fluosolmagnesiumrheoth RxabciximabadenosineHu 23F2G
glucose/insulin/KAMP 579
pexelizumabpexelizumab
TIMI 2TIMI 4TAMI 9ISIS 4COREMUNICHAMISTADHALT MIECLAADMIRECOMPLYCOMMA
TIMI 2TIMI 4TAMI 9ISIS 4COREMUNICHAMISTADHALT MIECLAADMIRECOMPLYCOMMA
nn
1.39050
43058.050
2.780200236420407311920814
1.39050
43058.050
2.780200236420407311920814
trialtrial
effect of GP IIb/IIIa inhibition on recovery of CBF and LV function
effect of GP IIb/IIIa inhibition on recovery of CBF and LV function
• peak CBF(cm/sec)
• peak CBF(cm/sec)
00
1010
abcixabcix
2020 18.118.1
10.410.4
control control
N 80N 80 N 7200
0.20.2
0.40.4
abcixabcix controlcontrol
N 79N 79 N 72
0.440.44
0.150.15
F.J. NEUMANN. Circulation 1998;98:2695-2701F.J. NEUMANN. Circulation 1998;98:2695-2701
p=0.024p=0.024• wall motion index (SD/chord)
• wall motion index (SD/chord)
p=0.007p=0.007
•2 weeks F/U vs post PCI measurements•2 weeks F/U vs post PCI measurements
the AMISTAD trialinfarct size
the AMISTAD trialinfarct size
KW MAHAFFEY. JACC 1999;34:1711-20KW MAHAFFEY. JACC 1999;34:1711-20
00
5050
adenn 72
adenn 72
placebon 72
placebon 72
15%15%
45%45%% of LV% of LV
2020
1010
3030
4040
anterior MIanterior MI% of LV% of LV
00
1010
adenn 119adenn 119
2020
13%13%
20%20%
placebon 117
placebon 117
55
1515
allall
direct stenting
n 102
direct stenting
n 102
angio end pointslow flow (TIMI 3 2)no-flow (TIMI 0-1)distal embolization
clinical outcomes (6-m F/U)deathre-MITVR
angio end pointslow flow (TIMI 3 2)no-flow (TIMI 0-1)distal embolization
clinical outcomes (6-m F/U)deathre-MITVR
direct stenting in acute MI direct stenting in acute MI
C. LOUBEYRE et al. JACC 2002;39:15-21C. LOUBEYRE et al. JACC 2002;39:15-21
11.7%2.9%4.9%3.9%
0.9%2.9%8.8%
11.7%2.9%4.9%3.9%
0.9%2.9%8.8%
pre-dilatation
n 104
pre-dilatation
n 104
26.9%12.5%
7.6%6.7%
3.8%3.8%6.7%
26.9%12.5%
7.6%6.7%
3.8%3.8%6.7%
p=0.01p=0.02
p=0.01p=0.02
angio end pointangio end point 11.7%11.7% 26.9%26.9%slow flow (TIMI 3 2)slow flow (TIMI 3 2)
2.9%2.9% 12.5%12.5%
endovascular coolingendovascular cooling
SR DIXON. JACC 2002;40:1928-34SR DIXON. JACC 2002;40:1928-34 COOL-MI n 400 ptsCOOL-MI n 400 pts
% pts% pts
00MACEMACE
1010
0%0%
10%10%
median infarct sizemedian infarct size
2%2%
8%8%
% LV% LV
55
00
1010
55
cooling n 21 cooling n 21 control n 21 control n 21
new cathether-based techniquesnew cathether-based techniques
thrombectomy
distal protection
thrombectomy
distal protection
mechanismmechanism CRTs in AMICRTs in AMIX-AMINE
AIMI
EMERALD
X-AMINE
AIMI
EMERALD
N 200N 200
N 500
PROMISE
N 200
N 500
PROMISE
N 200
devicedeviceX-SIZER•
ANGIOJET
PERCU-SURGE
FILTER-WIRE
X-SIZER•
ANGIOJET
PERCU-SURGE
FILTER-WIRE
• how to achieve optimal reperfusion
• what to do with the IRA found to be
occluded (on late angiography)
• the replacement of function of death cells
• how to achieve optimal reperfusion
• what to do with the IRA found to be
occluded (on late angiography)
• the replacement of function of death cells
current challengescurrent challenges
• what to do with the IRA found to be
occluded (on late angiography)
• what to do with the IRA found to be
occluded (on late angiography)
delayed PTCA for occluded IRA’sdelayed PTCA for occluded IRA’soutcomes: deathoutcomes: death
TAMI 6TOMIISPfistererHoriTOAT all
TAMI 6TOMIISPfistererHoriTOAT all
short termshort term
1 year F/U1 year F/UPfistererHoriTOAT all
PfistererHoriTOAT all
7144166666
263
7144166666
263
nn
166666
148
166666
148
8.8%4.0%
000
3.2%
8.8%4.0%
000
3.2%
PTCAPTCA
0000
0000
5.4%5.0%
05%0
3.6%
5.4%5.0%
05%0
3.6%
cons.cons.
05.0%
03.2%
05.0%
03.2%
00 0.50.5 1.51.511 22PTCA betterPTCA better cons. bettercons. better
1.69(0.21-15.7)1.69(0.21-15.7)
0.75(0.02-29.85)0.75(0.02-29.85)
0.0(0.0-3.64)0.0(0.0-3.64)
0.87(0.19-3.82)0.87(0.19-3.82)
0.0(0.0-3.64)0.0(0.0-3.64)
OR 95% CIOR 95% CI
0.01(0.0-4.4)0.01(0.0-4.4)
OOccluded ccluded AArtery rtery TTrial (OAT)rial (OAT)OOccluded ccluded AArtery rtery TTrial (OAT)rial (OAT)
1º endpoint: death/reMI/rehosp. CHF (NYA class IV) over 3 years1º endpoint: death/reMI/rehosp. CHF (NYA class IV) over 3 years
multicenter, randomized, controledmulticenter, randomized, controled
randomizationrandomization
n 3200 patientsoccluded IRA (TIMI 0,1)
n 3200 patientsoccluded IRA (TIMI 0,1)
PCI (3-28 days after MI) + risk factor modificationPCI (3-28 days after MI) + risk factor modification
no PCIno PCI
ASA-blockersACE inhibitors
ASA-blockersACE inhibitors
Apoptotic Rate in Occlued vs Open IRA
Abbate A et al. Circulation 2002
• how to achieve optimal reperfusion
• what to do with the IRA found to be
occluded (on late angiography)
• the replacement of function of death cells
• how to achieve optimal reperfusion
• what to do with the IRA found to be
occluded (on late angiography)
• the replacement of function of death cells
current challengescurrent challenges
TOPCARE-AMI
• hazards of stem cell manipulation
• arrhythmogenic potential of implanted cells
• hazards of stem cell manipulation
• arrhythmogenic potential of implanted cells
open questionsopen questions
• economic issues• economic issues
• the capacity of the stem cells to find their
optimal myocardial ‘niche’
• the capacity of the stem cells to find their
optimal myocardial ‘niche’
• long-term fate of transplanted cells in the
recipient heart
• long-term fate of transplanted cells in the
recipient heart• optimal timing for transplantation• optimal timing for transplantation