Primary angioplasty

1. EXPERTS WORKSHOP ON EARLY TREATMENT
STRATEGIES FOR ACUTE MYOCARDIAL INFARCTION
FOR THE MIDDLE EAST COUNTRIES
FEBRUARY 26
TH
-28
TH
2005 / DUBAI, UAE
SPONSORED BY BOEHRINGER INGELHEIM
SUNDAY, 27
th
FEBRUARY – SESSION 2
A rationale for pre-hospital thrombolytic therapy
Patrick Goldstein

2. Fire!
•Your house is on fire...

3. The Fire Spreads Quickly
•Every second is crucial, the damage is getting
worse

4. Transportation!?
•You are watching the firemen loading the
burning stuff...

5. To Extinguish the Fire!
•”Time is muscle and life!”

6. Cross-sections of left ventricle after experimental
coronary artery occlusion
(Reimer KA, et al. Circulation. 1977;56:786-794).
“Time is Muscle” 
Duration of
occlusion
3 h
Area supplied by
occluded artery
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
XXXX
Necrosis
Ischemic but viable
Non-ischemic
24 h
40
min
x
x
x
x
x
x
x
x
x
x
xx
x
x
x
x
xx
x
x
x
x

7. Acute MI again? Why?
· It is serious
· It’s desperately urgent
¸ We must act efficiently, in order to significantly
reduce mortality before arrival at the hospital
The diagnosis is clinical
ºThe strategy and the therapeutic management
are in constant movement

8. “Time is muscle”
MITI
4.9
11.2
14
12
10
8
6
4
2
0
Infarct Size (%)
< 70 min70-180
min

9. Estimated benefit (lives saved at 35
days) per 1000 patients
Time from onset (hours)
Mortality Reduction Depends on the Delay
“Onset of Pain - Thrombolytic Treatment”
Eric Boersma’s meta-analysis (22 trials from 83 to 93 - 50 246
patients)
BOERSMA, E. et al Early thrombolytic in acute myocardial treatment
infarction : reappraisal of the golden hour - Lancet 1996 ; 771 - 775
0 12 18 246
0
20
40
60
80
11
%
30 to 50 lives saved
for 1000 patients
1 to 3 hours
60 to 80 lives saved
for 1000 patients
30 to 60 min
1-month benefitDelay

10. Morrison’s Meta-analysis
• OBJECTIVE
•To realize a meta-analysis of randomized trials exploring
mortality in pre-hospital vs in-hospital thrombolysed AMI
INCLUDED STUDIES
•6 studies (n = 6 434)
• RESULTS
•Delay pain to treatment :
Pre-hospital thrombolysis = 104 min
In-hospital thrombolysis = 162 min (diff = 58 min)
(p=0.007)
•Significant reduction of the in-hospital death rate (all
causes) with pre-hospital thrombolysis : (- 17%)
(OR 0.83; 95% CI, 0.70-0.98).
JAMA, May 2000 - Vol 283 - N° 20 - 2686-92

11. Delay pain – treatment
French experience
1.601.592.102.102.353.033.032.503.03
200220011997200120022001200019951990
ESTIM
Nord
ESTIM IdFSTIM
SAMU
CAPTIMA3+A3A2G3GI

12. Material and Drugs of the SMUR
•Diagnostics:
ECG
Mini laboratory
•Therapeutics:
fibrinolytic
heparin
anti GP IIb/IIIa
aspirin
nitroglycerine
morphine
defibrillator
electric syringe
oxygen
and more

•Monitoring :
Scope Sao2

13. ASSENT-3 Plus (Pre-hospital Treatment)
Early treatment (ambulance-car) of AMI patients <6 hrs
ASA
RANDOMIZATION 1:1
TNK-tPA full dose
0.53 mg/kg bolus
Unfractionated heparin
60 IU/kg bolus (max. 4000 IU)
12 IU/kg/hr infusion (max 1000 IU/ hr)
target aPTT 50-70 sec
Patients’ outcome will be compared with matched pairs extracted from the
corresponding arm of the ASSENT-3 main study. The same exploratory
endpoints (single and composite) as in the ASSENT-3 main study will be
evaluated; the influence of time to treatment will be analyzed.
(500)
TNK-tPA full dose
0.53 mg/kg bolus
Enoxaparin
30 mg i.v. bolus
1 mg/kg s.c. twice a day
(500)

14. Hours to treatment (median)
3+
Symptom - callCall - arrivalArrival - Rand.
Rand. - first drugFirst drug - ER
01224364860728496108120132144156168
ENOX
UFH
ASSENT-3
In-hospital
Symptom – TNK
TNK
TNK
45 min

15. Thrombolysis or PTCA
still a debate ?

16. CAPTIM
Comparison of
Angioplasty and
Pre-hospital
Thrombolysis
In acute
Myocardial infarction
ESC 2001

17. M I C U - SMUR
CAPTIM Design
ST segment 
onset of pain < 6 h
All received ASA + Heparin
Central randomisation
In-hospital Pre-hospital
PCI thrombolysis
Diagnosis
positive in 95%

18. •Primary
•Composite (30 day)  all-cause mortality
 recurrent MI
 disabling stroke
•Secondary
• Cardiovascular death
• New onset of angina
• Urgent angioplasty
• Cardiogenic shock
• Hemorrhagic stoke
• Severe hemorrhage
CAPTIM - Clinical Endpoints

19. Primary endpoint %
Death (%)
Reinfarction (%)
Disabling stroke (%)
CAPTIM - Results primary endpoint
Pre-hospital
thrombolysis
n = 419
Primary
PCI
n = 421
8.2
RR = 0.76
3.8
3.7
1.0
6.2
RR = 0.76
4.8
1.7
0.0
P
Value
0.29
0.60
0.13
0.12

20. Cardiovascular death (%)
New onset of angina (%)
Urgent angioplasty (%)
Cardiogenic shock (%)
Hemorrhagic stoke (%)
Severe hemorrhage (%)
CAPTIM - secondary endpoints
Pre-hospital
thrombolysis
n = 419
Primary
PCI
n = 421
P
Value
3.8
7.2
33.0
2.5
0.5
0.5
4.3
4.0
4.0
4.9
0.0
2.0
0.86
0.09
< 0.01
0.09
0.49
0.06

21. DANAMI-2
DENMARK
5.4 mill. inhabitants
5 PCI centers
24 referral hospitals
62% of Danish
population
Transport distance
up to 95 US miles
(mean 35 miles)
100 US miles

22. DANAMI II
ACC 2002
5 PCI centers + 22 referring hospitals
distance average = 56 km
1129 patients 443 patients
referring hospitals PCI centers
no transferambulance PCI fibrinolysis
transfer on site
fibrinolysis
Very high risk patients: ST > 4 mm

23. Comparaison CAPTIM / DANAMI II
Thrombolysis PCI p
CAPTIM 8.2 % 6.2 % 0.29
DANAMI II combined 13.7 % 8.0 % 0.003
DANAMI II referring 14.2 % 8.5 %
DANAMI II invasive 12.3 % 6.7 % 0.048
Combined Death, ReMI and stroke

24. CAPTIM DANAMI II combined
PHT PCI thrombolysis PCI
Death 3.8 % 4.8 %7.6 % 6.6 %
Disabling 1.0 %0.0 % 2.0 % 1.1 %
stroke
Reinfarction3.7 %1.7 % 6.3 % 1.6 %
Look at the single endpoints: 30 days

25. Preventing Reinfarction :
IIb/IIIa Inhibitors, Enoxaparin, or Primary PCI
PRAGUE-2 30-day deaths 6.8 v 10.0 % , p = 0.12
* 6-month data in press, Simes AHU 2002
** Pre-hospital administration
p < 0.05 reMI, death (PCAT only) ; stroke (PCAT only)

CAPTIM
840
PCI t-PA**
DANAMI-2
1.572
PCI t-PA
C-PORT*
451
PCI t-PA
PCAT*
2.725
PCI lytic

Death 4.6% 3.7% 6.6% 7.6% 6.2% 7.1% 6.2% 8.2%

ReMI 1.7% 3.7% 1.6% 6.3% 5.3% 10.6% 4.8% 9.8%

Stoke 0 1.0% 1.1% 2.0% 2.2% 4.0% 0.7% 1.9%

26. DANAMI-2 vs CAPTIM vs ASSENT-3
Mortality at 30 days
%
(TNK + ENOX)
ESSAI TOTAL
6.6
4.8
7.6
3.8
5.4
5.8
0
2
4
6
8
DANAMI-2 CAPTIM ASSENT-3ASSENT3+
PCI
TT

27. Pre-Hospital
Lysis
Primary
PCI
Death
CAPTIM 1-Year Results
GW Symposium, AHA 2002
Death
Pre-Hospital
Lysis
Primary
PCI
Sx < 2 hours Sx > 2 hours
P=0.057 P=0.47
2.2%
5.7%
0%
5%
5.9%
3.7%
0%
10%

28. Pre-Hospital
Lysis
Primary
PCI
P=0.032
Shock Randomization to DC
CAPTIM 1 Year Results
GW Symposium, AHA 2002
P=0.0007
Shock Randomization to Adm
Pre-Hospital
Lysis
Primary
PCI
Sx < 2 hours Sx < 2 hours
1.3%
5.3%
0%
5%
0.0%
3.6%
0%

29. All presented periods are
median
Beginning
of pain
65 minEmergency
call at
SAMU
19 min
PEC
SMUR
Beginning of
thrombolysis
35 min
66 minArrival at
hospital
84 min
Puncture
According to ATLS:
32 min
120 min
185 min
E-MUST
Comparable periods

31. The Lille Experience
4h55
3h
3h
1h49
1h42
0 1 2 3 4 5 6
Thr. pre-hosp.
Thr. pre-hosp. +
angioplasty
Thr. hosp.
Thr. hosp.+
angioplasty
Angioplasty

32. USIC 2000
•French nationwide survey designed as a
multicenter, prospective longitudinal study over
one month
•Aim: to assess current practices and clinical
outcome in patients admitted to an ICU for AMI in
France
•Organisation :
• in-hospital outcome
• one-year follow-up

33. One-month Mortality in Patients
with Reperfusion Therapy: USIC 2000
n = 428 370 108
47 % 41 % 12 %
7.9 7.8
4.6
0
1
2
3
4
5
6
7
8
9
Primary PTCA IV lysis Lysis + PTCA

34. USIC 2000: One-month Mortality
in Patients with Reperfusion Therapy
n = 370 108 428
41% 12% 47%
7.1
9.6
3.0
5.8
3.6
7.9
0
2
4
6
8
10
12
Hosp. lysis
no PCI
Pre-hosp.
lysis no
PCI
Hosp. lysis
+ PCI
Pre-hosp.
lysis + PCI
Primary
PCI

35. Combined Strategy of
reperfusion

36. The Combined Strategies of Reperfusion
J.M. Julliard : A matched comparison of the combination of prehospital thrombolysis
and stand bye rescue angioplasty with primary angioplasty. Am.J. Cardiol. 1999 ; 83 -
305-310.
170 patients in Paris city
Pre-hospital Thrombolysis
Angiography at 80 min
TIMI 3
108 (64%)
TIMI 2
12 (7%)
TIMI 0
50 (29%)
angioplasty
TIMI 3
91%
TIMI 2
7%

37. Which Delays for This Technique of Combined
Reperfusion
PHT Admission = 58 ± 20 min
Admission Angiography = 59 ± 19 min
Then
2 h after PHT
only 2% of patients
are TIMI O or 1

38. Outcome after Combined Reperfusion Therapy for AMI, Combining
Pre-hospital Thrombolysis with Immediate PTCA and Stent
1995-1999
1010 patients
with AMI
(Paris Sud Cardiovascular Institute)
148 patients
with pre-hospital full-dose thrombolytic
therapy
131 patients included
(median time = 2 h after onset of pain)
C. Loubeyre and all. Eur. Heart J. 2001 ; 22 : 1128-1135

39. 131 patients
Angiography 95 min
after TT
64 (49%)
TIMI 3
54 (84%)
PTCA
65 (50%)
TIMI 0 - 2
PTCA
119 (91%) PTCA
114 stent
120/131 TIMI 3 (92%)
9/131 TIMI 2
2 TIMI 0-1
no emergency surgery
From C. Loubeyre

40. Long-term follow-up
2 ± 1 year
mortality rate : 6% (8 patients)
non-fatal re MI : 2 patients
survival + no RI rate
= 90%
94 patients (70%) symptom free
- no re-hospitalization
- no revascularization
C. Loubeyre. Eur. Heart J. 2001 ; 22 : 1128-1135

41. Early PCI versus Guided PCI
after Lytics in the Modern Era
Death
Relative risk, fixed model
Bilateral CI, 95% for trials, 95% for MA
SIAM III 0.44 [0.14;1.37]
GRACIA-1 0.57 [0.26;1.26]
CAPITAL-AMI 0.67 [0.11;3.89]
Total 0.54 [0.29;0.99] 0.047
Cochran Q het. p=0.91
Rel. Risk0 1 2 34
0.538, p=0.047
RR CI p

42. RESCUE 0.53 [0.16;1.75]
REACT 0.51 [0.24;1.10]
MERLIN 1.14 [0.59;2.20]
LIMI 0.84 [0.27;2.65]
Belenkie et al 0.19 [0.02;1.47]
Total 0.73 [0.48;1.11] 0.138
Cochran Q het. P=0.33
Rescue PCI after Lytics
Death 6 weeks
Relative risk, fixed model
Bilateral CI, 95% for trials, 95% for MA
Rel. Risk 0.41.01.62.2
RR CI p

43. Conclusion
•Pre-hospital thrombolysis is still the gold standard
•Very high risk patients MUST have a PCI with a
minimum delay
•Transfer is not an additional risk

Pre-hospital thrombolysis + Angioplasty

44. Pre-hospital thrombolysis
+ immediate angioplasty
+ stent implantation
is safe and effective
EP. Mc Fadden. Eur. Heart J. 2001 ; 22 : 1067-69