Primary PCI

1
Primary PCI The Preferred Reperfusion
Therapy for AMI
Victor Guetta, M.D. Sheba Medical Center,
Tel-Hashomer
2
Why does fibrinolysis work?

• Restores patency of IRA
• Salvages myocardium
• Prevents unfavorable remodeling
• Diminishes electrical instability
• Preserves collateral potential
• Universally available

3
Early mortality in AMI
Anderson, AJC, 1996
4
Redefining the Standard of Acute Angiography

• Meta-analysis of 60-minute angiography
• 12 trials
• 19891998
• 1613 patients
• SK, r-PA and t-PA
• Weighted pooled analysis with 95 confidence
  intervals

5
Redefining the Standardof Acute Angiography
60 minutes 90 minutes

GUSTO-I angio at 90 minutes
6
Redefining the Standardof Acute Angiography
GUSTO-I 90-min
Meta-analysis 60-min
23
23
p lt 0.001
SK
t-PA
SK
t-PA
NEJM 1993
7
Intracranial Hemorrhage

• Thrombolytic therapy induces a relatively high
  rate of intracerebral hemorrhage
• 1 in 100 to 200 treated patients (0.7)
  

8
Procoagulant Effects of Thrombolytic Therapy
Fibrin-Thrombin
Platelets
Fibrin-Thrombin
Fibrinolytic
Thrombin increases platelet aggregation
Thrombin begets
thrombin
Platelets
Resistance to
PAI-1
PAI-1
fibrinolysis
No response to fibrinolytic
Adapted with permission from Topol EJ.
Circulation. 199897211-218.
9
Combination therapy in AMI

• Completed studies
• TIMI 14
• SPEED
• INTRO-AMI
• INTEGRITI
• GUSTO V AMI
• ASSENT III

• On-going studies
• FASTER
• ENTIRE

10
Breaking the ceiling of fibrinolysis

• Combination fibrin and platelet lysis has been
  shown to enhance arterial patency in AMI

180/90/1.33
11
GUSTO V
12
Why does fibrinolysis not work?

• Minimal thrombus in 15-25
• Reocclusion
• Platelet activation
• Thrombin
• Vasomotor instability
• Resistance to lysis - time and composition
• Does not alleviate flow-limiting fixed stenoses
• Does not restore tissue perfusion in 20-30
  (TIMI 0-I)

13
DESCRIPTION OF THE TRIALS COMPARING PRIMARY PTCA
AND INTRAVENOUS THROMBOLYSIS
14
Death and nonfatal reinfarction at the end of
study period
15
Mortality at the end of study period
16
Overview of Primary PTCA versus Thrombolytic
Therapy

• 10 trials
• 2606 patients
• 74 mins to primary PTCA

Events Relative Prevented/1000
Reduction p Pts Treated Mortality 32 0.02 21 R
einfarction 45 0.04 24 IC Bleed 91 lt 0.001 10
Weaver, JAMA 1997
17
Reperfusion therapy for AMI
30-d outcome
Weaver,JAMA 19972782093
18
Acute MI
PTCA vs Lysis 6 Month

8.2
6.2
11 RCTs (2725 patients)
PCAT Collaborative Group, 2001
19
Acute MI
PTCA vs Lysis 6 Month

16.1
10.2
11 RCTs (2725 patients)
PCAT Collaborative Group, 2001
20
Acute MI
PTCA vs Lysis 6 Month

Subgroups n PTCA () Lytic () Relative Risk (95
Cl) Treatment Delay (mins)lt 35 724 4.7 15.735-
55 1152 7.9 12.5gt 55 733 8.3 12.1 Site Volume
Low 1533 8.7 12.7Medium 601 5.8 14.0High 501 3
.6 13.5
p 0.06
p 0.03
average time difference between
commencingthrombolytic therapy and performing
first balloon inflation at an individual site
level. Site volume on-study only, classified
by number of patients randomized to PTCA per
site per year Low lt 15 patients/site
year Medium 15-30 patients/site/year High
gt 30 patients/site/year
11 RCTs (2725 patients)
PCAT Collaborative Group, 2001
21
Acute MI
PTCA vs Lysis 6 Month

PTCA () Lytic () Relative Risk (95
Cl) MortalityIn-hospital 4.0 6.3 30
days 4.3 6.96 months 6.2 8.2 Re-MIIn-hospital 2.
5 6.430 days 3.2 7.66 months 4.8 9.8 Death
Re-MIIn-hospital 6.1 11.730 days 7.0 12.96
months 10.2 16.1 Total StrokeIn-hospital 0.22 1.4
530 days 0.66 1.88
11 RCTs (2725 patients)
PCAT Collaborative Group, 2001
22
Acute MI
PTCA vs Lysis 6 Month

Subgroups n PTCA () Lytic () Relative Risk
(95 Cl) Agelt 60 1178 4.3 8.260-70 852 6.3 12.8
gt 70 605 13.3 23.6 Sex Male 2043 5.7 12.2Female
591 11.7 16.4 Diabetes Yes 367 9.2 19.3No 2151 6
.5 11.8 Prior MIYes 383 9.7 22.7No 2250 6.6 11.5
MI locationAnterior 1153 8.2 14.5Non-anterior 1
469 6.2 12.0
11 RCTs (2725 patients)
PCAT Collaborative Group, 2001
23
Acute MI
PTCA vs Lysis

Subgroups n PTCA () Lytic () Relative Risk
(95 Cl) Pulse rate lt 65 678 5.3 13.4 65-75 513
8.2 9.7 75-85 536 6.6 12.9 85 690 8.2 14.6 SBP
(mmHg) lt 115 595 10.5 17.4 115-130 480 5.3 10.3
130-150 737 7.8 10.4 150 612 4.5 14.0 Risk
group Low 1186 2.9 7.2 Intermediate 758 8.0 12.
7 High 691 13.1 24.1 Presentation time 0 - lt
2 838 5.6 11.6 2 - lt 4 1035 8.2 12.6 4 - lt
6 347 6.0 15.6 6 hrs 265 8.5 21.3
PCAT Collaborative Group, 2001
11 RCTs (2725 patients)
24
Advances in reperfusion

• Stents
• Anti-platelet agents
• As adjunct to primary angioplasty
• In combination with fibrinolysis
• As precursor to facilitated angioplasty
• Combination

25
Stents in primary PCI
26
Reperfusion in AMI
Schomig, NEJM 2000343385
27
Effective reperfusion in AMI
Schomig, NEJM 2000343385
28
Myocardial salvage index
Time from symptom onset to reperfusion
Schomig, NEJM 2000343385
29
Abciximab in primary angioplasty
30-day death/MI/urgent TVR
Plt0.01 for all
30
CADILLAC
Presentation of acute safety / outcome data

• No difference between groups in mortality,
  stroke
• Trend toward fewer reinfarctions in stent pts
• Trend toward less ischemia-driven TVR in stent
  pts
• No difference between groups in ICH

Stent/A Stent/P PTCA/A PTCA/P TIMI 3 flow
96.7 92.1 95 94.8 Rec isch 1.2 3.9
1.4 4 Bleeding 4.5 3.5 5.1 3.1
Stone. Oral presentation. AHA 1999.
31
CADILLAC
MACE at 6 Months
20
19.3
15.2
15
10.9
10.8
10
Incidence ()
5
0
0
30
60
90
120
150
180
Days to event
PTCA, no abx
PTCA, abx
Stent, no abx
Stent, abx
Stone et al. Circ 2000 102 II-664
32
ADM IRAL and CADILLAC
Stone et al. Circ 2000 102 II-664, Barragan et
al Circ 2000 102 II-662
TIMI 3 Flow
p NS
p 0.04
p NS
p 0.01
ADMIRAL
CADILLAC
33
ADM IRAL and CADILLAC
Stone et al. Circ 2000 102 II-664, Barragan et
al Circ 2000 102 II-662
6 Month Mortality
? 55
? 14
34
ADMIRAL vs CADILLAC
35
Primary Stenting With or Without Abciximab
Cardiac Function Parameters at 14 Days
25
80
0.8
P
0.003
P
0.007
P
0.024
70
62
20
18.1
56
60
0.6
50
0.44
15
global LVEF ()
40
10.4
0.4
10
30
0.15
20
0.2
5

10
0
0
0
n72
n80
n79
n72
n72
n79
no abciximab
abciximab
36
Meta-analysis of abciximab benefit in AMI
A P 684 685
Khot, ACC 2001
37
Facilitated PCI
PCI soon after pharmacotherapy, with or without
persistent ischemia
38
SPEED-Facilitated PCI
Freedom from D/MI/UR
MACE at 30 days
Hermann, JACC 2000 361489
39
Arterial patency before PCI
Plt0.0001
P0.02
Brodie, AJC 20008513
40
SPEED - Facilitated PCI
N99
N195
Hermann, JACC 2000 361489
41
Evaluation of Myocardial Perfusion

• 1. ST Resolution Schröder JACC 26 1657,1995
• Complete (gt70) Partial (30-70) None (lt 30)
• 2. TIMI Myocardial Perfusion Grade (MPG)

TMP Grade 0
TMP Grade 1
TMP Grade 2
TMP Grade 3
No or minimal blush
Stain present. Blush persists on next injection
Dye strongly persistent at end of washout. Gone
by next injection
Normal ground glass appearance of blush. Dye
mildly persistent at end of washout
CM Gibson Circulation 1999
42
Microvascular obstruction
Fibrinolysis/PCI

• MVO
• Platelets
• Plaque

ST elevation High cTFC MCO defect MRI defect
TIMI 3 flow
43
Tissue reperfusion after fibrinolysis
TMP and 30-day mortality
Gibson, Circulation 2000
44
A union in reperfusion

• Open vasculature hypothesis is now a more
  appropriate term than open artery hypothesisIt
  would be logical to offer the best of the two
  complementary strategies.

Gibson, JACC 2000361497
45
Preventing Distal Embolization

• 34 y.o. female presenting with acute anterior MI
  less than 2 hours from symptoms onset

46
Preventing Distal Embolization

• Give ASA and Heparin (ACT 200-250 sec)
• Start GP IIb/IIIa inhibitors

47
Preventing Distal Embolization

• Use X-Sizer or Insert embolic protective device
• Check the flow

48
Preventing Distal Embolization

• Treat the artery Direct stenting if possible

49
Preventing Distal Embolization

• Final result

50
New paradigm of reperfusion

• Improves speed and quality of reperfusion
• Prevents and attenuates consequences of distal
  embolization of plaque and thrombus
• Facilitates immediate revascularization
• Prevents reocclusion and reinfarction

Do Facilitated Primary PCI !!
51
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