STRATEGIE NELLA RIPERFUSIONE PRECOCE DELLO STEMI:

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STRATEGIE NELLA RIPERFUSIONE PRECOCE DELLO STEMI

• PTCA FACILITATA

Dott Antonio Giomi Emodinamica ASL 3 Pistoia
Villa Cappugi, Pistoia 29 nov-1dic 2007
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Time to Reperfusion and Outcome
B-C benefit ?
A-C benefit
D-C harm
Time to treatment is critical
Opening the IRA PPCIgtlysis
Gersh JAMA 2005
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Optimal therapeutic strategies in community
hospitals without facility for PPCI drip or
ship?

• Duration of symptoms
• Haemodynamic instability
• Risk of (intracranial) bleeding
• Transport delays PCI related delay (door to
  baloon door to needle)

B Gersh EM Antman Eur Heart J 27761, 2006
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Tcheng J Am Coll Cardiol 481336, 2006
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DRIP SHIP
Tcheng J Am Coll Cardiol 481336, 2006
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Facilitated PCI definition
Administration of a pharmacological substance
before planned immediate PCI with the intent to
improve the coronary patency before the proceure.
This approach is based on the hypotesis that
pharmaco- induced reperfusion will occur during
the time needed to transfer the patient to a
facility for PCI and that this early reperfusion
will result in smaller infarct,
higher Procedural success rate , better clinical
outcome
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Background of Facilitated PCI

• PCI related delay and its negative impact on
  outcome
• Advantage of an open vessel before PCI

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Motality benefit of primary PCI declines with
PCI-related time delay
10 -
13 RCTs
N 5494
P 0.04
5 -
Favors PCI
Mortality equipose 60 min
Absolute Risk Difference in Death ()
0 -
Favors fibrinolysis with a fibrin-specific agent
-5 -
-
-
-
-
-
-

• 40 50
  60 70 80

PCI-Related Time Delay (minutes)
Nallamothu and Bates. Am J Cardiol 200392824.
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Motality benefit of primary PCI declines with
PCI-related time delay
10 -
13 RCTs
N 5494
P 0.04
5 -
Favors PCI
Mortality equipose 60 min
Absolute Risk Difference in Death ()
0 -
Favors fibrinolysis with a fibrin-specific agent
-5 -
-
-
-
-
-
-

• 40 50
  60 70 80

PCI-Related Time Delay (minutes)
Nallamothu and Bates. Am J Cardiol 200392824.
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Normal flow (TIMI-3) before mechanical
reperfusion therapy is an important determinant
of survival in Acute Myocardial Infarction
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AHA/ACC Guidelines 2004
Although preliminary studies have not shown a
benefit, a strategy of facilitated PCI holds
promise in higher- risk patients when PCI is not
immediately available (class IIb indication)
ESC PCI guidelines 2005
At the moment , there is no evidence for
recomendation of thrombolysis-facilitated PCI or
GPIIb/IIIa Inibitors- Facilitated PCI
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Trials that have compared Primary PCI with
Facilitated PCI
GPIIbIIIa Full dose lytic Combo
Therapy antagonist ½ dose lytic
IIbIII3 ant
ADVANCE-MI Brave FINESSE
On-Time Tiger-PA ERAMI ROMOBILE Zorman et
al Cutlip et Al INTAMI Bellandi FINESSE
ASSENT 4-PCI SAMI Prague LIMI PACT Gracia 2
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ASSENT- 4 PCI study design
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ASSENT- 4 PCI Trial TIMI Flow Grade
TIMI grade 3 flow prior to PCI and TIMI grade 2/3
flow post-PCI ()
p0.03

• TIMI grade 3 flow prior to PCI was present more
  frequently in the TNK PCI arm (43.6 vs 15.0)
• TIMI grade 2/3 post-PCI was slightly higher in
  the PCI alone group (95.3 vs 97.6)

plt0.001
Presented at ESC 2005
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ASSENT-4 90-day combined endpoint
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ASSENT-4 90-day mortality results
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ASSENT-4 PCI in-hospital cardiac events
van de Werf F. European Society of Cardiology
Congress 2005 September 4-7, 2005 Stockholm,
Sweden.
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ASSENT-4 PCI in-hospital stroke rates
van de Werf F. European Society of Cardiology
Congress 2005 September 4-7, 2005 Stockholm,
Sweden.
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ASSENT- 4 PCI in-hospital stroke rates
4 22 1 6 8 1 5
4 17 3 5 0 3 3
van de Werf F. European Society of Cardiology
Congress 2005 September 4-7, 2005 Stockholm,
Sweden.
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ASSENT- 4 PCI causes of death
TNK PCI PCI alone n55
n40
Reinfarction Cardiogenic shock Asystole /cardiac
arrest Cardiac rupture/EMD Stroke/ ic
hemorrhage Other cardiac event Other non cardiac
event
4 22 1 6 8 1 5
4 17 3 5 0 3 3
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ASSENT 4-PCI Relative risk for primary endpoint
in subgroups
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ASSENT 4 PCI first medical contact(site of
randomizzation)
20 n326
45 n735
35 n565
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ASSENT 4 PCI first medical contact vs mortality
Subgroup analysis of mortality based on site of
randomization ()
n754
n588
n325
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Comparison of delay in different trials with
fibrinolytic facilitation strategy
Pain - angiography
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Assent 4 PCI why negative results?

• Open artery hypothesis is wrong
• Reduced efficacy of lytic if not given very early
  (gt50 beyond 2 hours)
• Suboptimal antithrombotic co-therapy (UFH
  infusion/clopidogrel/GPIIbIIIa)
• PCI performed shortly after lytic (mean 103 min)
  in a pro-thrombotic environment
• Impact of intracranial hemorrage in lytic treated
  patients
• Wrong study population

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TIMI Flow in IRA Pre-PCI
Subjects with TIMI 2/3 (Patency) Pre-PCI

p lt 0.0001
p lt 0.0001
61
Percentage
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TIMI 2 TIMI 3
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25
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36
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15
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Abciximab Facilitated PCI (n809)
Primary PCI (in lab Abciximab) (n790)
Reteplase/Abciximab Facilitated PCI (n815)
Ave Time from First Abciximab Bolus
74 min 76 min
to Angiogram in Facilitated Groups
Modified ITT Population with Index PCI ITT, PCI
and any dose of study drug (active or placebo)
Investigator assessment
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FINESSE Results Primary and Secondary Endpoints
All cause mortality rehospitalization or ED
treatment for CHF resuscitated ventricular
fibrillation occurring gt 48 hours after
randomization cardiogenic shock
EDemergency department
Ellis S. European Society of Cardiology Congress
2007 September 3, 2007 Vienna, Austria
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FINESSE Results Primary and Secondary Endpoints
All cause mortality rehospitalization or ED
treatment for CHF resuscitated ventricular
fibrillation occurring gt 48 hours after
randomization cardiogenic shock
EDemergency department
Ellis S. European Society of Cardiology Congress
2007 September 3, 2007 Vienna, Austria
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FINESSE Results Safety (Bleeding) Endpoints
Ellis S. European Society of Cardiology Congress
2007 September 3, 2007 Vienna, Austria
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FINESSE Results Safety (Bleeding) Endpoints
Ellis S. European Society of Cardiology Congress
2007 September 3, 2007 Vienna, Austria
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gt15 mm ST (or 2nd MI, Killip 2-3, LVEFlt35)
lytic eligible, lt 12 h
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Può una strategia farmacologica a
monte Facilitare una PCI primaria ?
Può una PCI successiva migliorare loutcome
dopo una iniziale strategia farmacologica ?
SI
NO
PCI facilitata
Strategia farmaco invasiva