11

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