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Controversia: Controversia: La Terapia Facilitante con La Terapia Facilitante con
Trombolisi nell’Infarto Acuto del Trombolisi nell’Infarto Acuto del Miocardico Miocardico
Alberto Genovesi EbertAlberto Genovesi EbertSpedali Riuniti, LivornoSpedali Riuniti, Livorno
ControContro
22
•TeoriaTeoria
•MetanalisiMetanalisi
•RCTRCT
Controversia: Controversia: La Terapia Facilitante con La Terapia Facilitante con
Trombolisi nell’Infarto Acuto del Trombolisi nell’Infarto Acuto del Miocardico Miocardico
ControContro
33
Controversia: Controversia: La Terapia Facilitante con La Terapia Facilitante con
Trombolisi nell’Infarto Acuto del Trombolisi nell’Infarto Acuto del Miocardico Miocardico
ControContro
•TeoriaTeoria
•MetanalisiMetanalisi
•RCTRCT
44
Sites of Anti-thrombotic Sites of Anti-thrombotic Drug ActionDrug Action
Tissue factorTissue factor
Plasma clottingPlasma clottingcascadecascade
ProthrombinProthrombin
ThrombinThrombin
FibrinogenFibrinogen FibrinFibrin
ThrombusThrombus
Platelet aggregationPlatelet aggregation
Conformational Conformational activation of GPIIb/IIIaactivation of GPIIb/IIIa
CollagenCollagen
Thromboxane AThromboxane A22
ADPADP
ATAT
ATAT
AspirinAspirin
TiclopidineTiclopidineClopidogrelClopidogrel
GPIIb/IIIaGPIIb/IIIainhibitorsinhibitors
FactorFactorXaXa
BivalirudinBivalirudinHirudinHirudin
ArgatrobanArgatroban
LMWHLMWHHeparinHeparin
Thrombo-Thrombo-lyticslytics
CoagulationCoagulationcascadecascade
PlateletPlateletcascadecascade
55Copyright ©1998 American Heart Association
Hoffmeister, H. M. et al. Circulation 1998;98:2527-2533
Levels of TAT complexes as marker of thrombin generation in patients with AMI and streptokinase, alteplase, or no thrombolytic
therapy compared with control subjects (contr)
66
Fibrinolisi e CoagulazioneFibrinolisi e Coagulazione
Granger CB JACC 98;31: 497 Granger CB JACC 98;31: 497
77
Thromb Haemost 1997;78:214-219
Fibrinolisi, Coagulazione e Fibrinolisi, Coagulazione e PiastrinePiastrine
88
ASSENT IVASSENT IV
0
2
4
6
8
Urg. Rivasc. Re AMI
Fac TNK PPCI
Lancet 06: 367: 569Lancet 06: 367: 569
p=.027p=.027p=.0041p=.0041
99
Controversia: Controversia: La Terapia Facilitante con La Terapia Facilitante con
Trombolisi nell’Infarto Acuto del Trombolisi nell’Infarto Acuto del Miocardico Miocardico
ControContro
•TeoriaTeoria
•MetanalisiMetanalisi
•RCTRCT
1010
Keeley EC Lancet 06; 367: 579Keeley EC Lancet 06; 367: 579
PCI After LyticsPCI After Lytics““Facilitated Angioplasty: Paradise Lost”?Facilitated Angioplasty: Paradise Lost”?
Fac. BetterFac. Better PPI BetterPPI Better
totaltotal
1111
Keeley EC Lancet 06; 367: 579Keeley EC Lancet 06; 367: 579
PCI After LyticsPCI After Lytics““Facilitated Angioplasty: Paradise Lost”?Facilitated Angioplasty: Paradise Lost”?
Fac. BetterFac. Better PPI BetterPPI Better
totaltotal
totaltotal
1212
•Facilitazione con Fibrinolisi Facilitazione con Fibrinolisi
“Intera”? “Intera”?
•No!No!
•Spazio per il “mezzo e mezzo”?Spazio per il “mezzo e mezzo”?
1313
Focus on ½ Lytics + Anti Focus on ½ Lytics + Anti 2b/3a2b/3a
Sinno MCN AHJ 07; 153: 579Sinno MCN AHJ 07; 153: 579
1414
SanguinamentiSanguinamenti
Fac. BetterFac. Better PPI BetterPPI Better
Sinno MCN AHJ 07; 153: 579Sinno MCN AHJ 07; 153: 579Keeley EC Lancet 06; 367: 579Keeley EC Lancet 06; 367: 579
1515
PTCA Iaria vs Txlisi: Ictus PTCA Iaria vs Txlisi: Ictus Emorragici Emorragici
0
0,02
0,04
0,06
0,08
0,1
TrLy
PPCI
Keeley EC Lancet 2003;361:13Keeley EC Lancet 2003;361:13
Lytic (n=3867) Lytic (n=3867) PTCA (n=3872)PTCA (n=3872)
p=0.032p=0.032
1616
PTCA Iaria vs Txlisi: Ictus PTCA Iaria vs Txlisi: Ictus Emorragici Emorragici
0
0,02
0,04
0,06
0,08
0,1
TrLy
PPCI
Keeley EC Lancet 2003;361:13Keeley EC Lancet 2003;361:13
Lytic (n=3867) Lytic (n=3867) PTCA (n=3872)PTCA (n=3872)
p=0.032p=0.032
……e la facilitata?e la facilitata?
1717
StrokesStrokes
Keeley EC Lancet 06; 367: 579Keeley EC Lancet 06; 367: 579
1818
•TeoriaTeoria
•MetanalisiMetanalisi
•RCTRCT
Controversia: Controversia: La Terapia Facilitante con La Terapia Facilitante con
Trombolisi nell’Infarto Acuto del Trombolisi nell’Infarto Acuto del Miocardico Miocardico
ControContro
1919
Abciximab Placebo Placebo
Follow up through 90 days and 1 year
Primary PCI with Abciximab Infusion (12 h)
FINESSE: Study DesignFINESSE: Study Design
Acute ST Elevation MI (or New LBBB) within 6h pain onsetAcute ST Elevation MI (or New LBBB) within 6h pain onset
Presenting at Hub or Spoke with estimated time to Cath between 1 and 4 hoursPresenting at Hub or Spoke with estimated time to Cath between 1 and 4 hours
PlaceboPlacebo
Reteplase (5U+5U)*Abciximab
PlaceboAbciximab
Randomize 1:1:1N=3000 *Only 5U if 75 yr
Transfer To Cath LabASA, unfractionated heparin 40U/kg (max 3000U)
or enoxaparin (0.5 mg/kg IV + 0.3 mg/kg SC) – substudy only
Double BlindDouble Dummy
Ellis SG NEJM 08; 358: 2205Ellis SG NEJM 08; 358: 2205
2020Ellis SG NEJM 08; 358: 2205Ellis SG NEJM 08; 358: 2205
Death/Cardiogenic Shock/CHF (H/ED)@90days/VF>48hDeath/Cardiogenic Shock/CHF (H/ED)@90days/VF>48h
2121
% Subjects with Event through Day 90
4,5%
2,2%
6,8%
0,4%
5,5%
2,9%
4,8%
0,2%
5,2% 5,3%
0,6%
1,9%
0%
2%
4%
6%
8%
10%
Death CHF RequiringHosp/ED visit
CardiogenicShock
VF >48H
Pe
rce
nta
ge
Primary PCI with In Lab Abciximab (n=806)Abciximab Facililated PCI (n=818)Abciximab/Reteplase Facilitated PCI (n=828)
Finesse: EfficaciaFinesse: Efficacia
Ellis SG NEJM 08; 358: 2205Ellis SG NEJM 08; 358: 2205
2222
% Subjects with Recurrent MI through Day 90
1,9% 2,0% 2,1%
0%
2%
4%
6%
8%
10%
Per
cen
tag
e
Primary PCI with in lab Abciximab (n=806)Abciximab Facililated PCI (n=818)Abciximab/Reteplase Facilitated PCI (n=828)
Finesse: EfficaciaFinesse: Efficacia
Ellis SG NEJM 08; 358: 2205Ellis SG NEJM 08; 358: 2205
2323
Finesse: SicurezzaFinesse: Sicurezza
TIMI Bleeding through Discharge/Day 7
2,6%4,3%
6,9%
4,1%6,0%
10,1%
4,8%
9,7%
14,5%
0%
5%
10%
15%
20%
25%
30%
TIMI Major TIMI Minor TIMI Major or Minor
Pe
rce
nta
ge
Primary PCI with In Lab Abciximab (n=795)
Abciximab Facililated PCI (n=805)
Abciximab/Reteplase Facilitated PCI (n=814)
P<.05P<.05P<.05P<.05P<.05P<.05
Ellis SG NEJM 08; 358: 2205Ellis SG NEJM 08; 358: 2205
2424
FINESSE: Sanguinamenti e FINESSE: Sanguinamenti e PrognosiPrognosi
0
5
10
15
20
Mortalità
No Sang. Sang. Minori Sang. Maggiori
Ellis SG NEJM 08; 358: 2205Ellis SG NEJM 08; 358: 2205
2525
Facilitazione con Trombolisi? Facilitazione con Trombolisi?
Vantaggi? Vantaggi? No No Rischi?Rischi? SiSi
2626
2727Copyright ©2008 American Heart Association
White, H. D. Circulation 2008;118:219-222
Impact of PCI with fibrinolytic therapy
2828
Stroke through Discharge/Day 7
0,1%
0,9% 1,0%
0,0%0,0%
0,5% 0,5%
0,0%
0,6% 0,5%
1,1%
0,4%
0%
1%
2%
3%
4%
5%
ICH (n=6) Ischemic (n=15) Total Stroke(n=21)
Fatal Stroke(n=3)
Pe
rce
nta
ge
Primary PCI with In Lab Abciximab (n=795)
Abciximab Facililated PCI (n=805)
Reteplase/Abciximab Facilitated PCI (n=814)
Finesse: SicurezzaFinesse: Sicurezza
2929
3030
AS
SEN
T 4
AS
SEN
T 4
3131
AS
SEN
T 4
AS
SEN
T 4
3232
ASSENT IVASSENT IV
3333
Keeley EC Lancet 06; 367: 579Keeley EC Lancet 06; 367: 579
PCI After LyticsPCI After Lytics““Facilitated Angioplasty: Paradise Lost”?Facilitated Angioplasty: Paradise Lost”?
Fac. BetterFac. Better PPI BetterPPI Better
3434
Keeley EC Lancet 06; 367: 579Keeley EC Lancet 06; 367: 579
PCI After LyticsPCI After Lytics““Facilitated Angioplasty: Paradise Lost”?Facilitated Angioplasty: Paradise Lost”?
Fac. BetterFac. Better PPI BetterPPI Better
3535
Ictus Emorragici Trombolisi e PTCA Ictus Emorragici Trombolisi e PTCA Primaria Primaria
0
0,02
0,04
0,06
0,08
0,1
TrLy
PPCI
Keeley EC Lancet 2003;361:13Keeley EC Lancet 2003;361:13
Lytic (n=3867) Lytic (n=3867) PTCA (n=3872)PTCA (n=3872)
p=0.032p=0.032
3737
SanguinamentiSanguinamenti
Fac. BetterFac. Better PPI BetterPPI Better
Sinno MCN AHJ 07; 153: 579Sinno MCN AHJ 07; 153: 579Keeley EC Lancet 06; 367: 579Keeley EC Lancet 06; 367: 579
3838Keeley EC Lancet 06; 367: 579Keeley EC Lancet 06; 367: 579
PCI After LyticsPCI After Lytics““Facilitated Angioplasty: Paradise Lost”?Facilitated Angioplasty: Paradise Lost”?
Fac. BetterFac. Better PPI BetterPPI Better
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