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Diagnostic et Diagnostic et Prise Prise en Charge des en Charge des Echecs Echecs De Thrombolyse De Thrombolyse

Antoine Sarkis, MD

Jeudi 24 Novembre 2005

Diagnostic et Diagnostic et Prise Prise en Charge des en Charge des Echecs Echecs De Thrombolyse De Thrombolyse

• Modalit

Modalité és s de de traitement traitement de de l l’ ’infarctus infarctus aigu aigu du du myocarde myocarde (AMI) (AMI)

• Thrombolyse

Thrombolyse

• Vari

Varié ét té és s d d’ ’angioplastie angioplastie (PCI) (PCI) dans dans AMI AMI

• Crit

Critè ères res d d’é ’échec chec de thrombolyse de thrombolyse

• Angioplastie

Angioplastie apr aprè ès s é échec de thrombolyse chec de thrombolyse

PCI in AMI p-PTCA a-PTCA t

• P

T C A f-PTCA r-PTCA d-PTCA

Vari Varié ét té és s de PTCA in AMI de PTCA in AMI

• Primary

Primary (P (P-

• PTCA)

PTCA)

• Transfer

Transfer (T (T-

• PTCA)

PTCA)

• Facilitated PCI

Facilitated PCI–– ––after reduced dose after reduced dose lytics lytics alone, alone,

• r with
• r with IIb/IIIa

IIb/IIIa inhibitors inhibitors (F (F-

• PTCA)

PTCA)

• PCI early after

PCI early after thrombolytic thrombolytic therapy therapy

• Routine

Routine-

• immediately after

immediately after-

• (Adjunctive)

(Adjunctive) (A (A-

• PTCA)

PTCA)

• Rescue

Rescue – – in pts with persistent occlusion or reduced in pts with persistent occlusion or reduced flow in the infarct artery flow in the infarct artery (R (R-

• PTCA)

PTCA)

• Delayed

Delayed— — hours to days later hours to days later (D (D-

• PTCA)

PTCA)

P P-

• PTCA=Primary PTCA

PTCA=Primary PTCA

9,30% 7% 6,80% 2,50% 2% 1% 14,50% 8,20% 21% 6%

0,00% 5,00% 10,00% 15,00% 20,00% 25,00%

Death re-MI Stroke Combined Ischemia

Thrombolysis PCI

PCI PCI v/s v/s Thrombolysis in STEMI : Thrombolysis in STEMI : « « A quantitative review of 23 randomized trials A quantitative review of 23 randomized trials » »

Short Short-

• term Results

term Results

Keeley et al. Lancet 2003;361:13-20

P P-

• PTCA=Primary PTCA

PTCA=Primary PTCA

12,80% 9,60% 10% 4,80% 19% 12% 39% 22%

0,00% 5,00% 10,00% 15,00% 20,00% 25,00% 30,00% 35,00% 40,00% Death re-MI Combined Ischemia Thrombolysis PCI

PCI PCI v/s v/s Thrombolysis in STEMI : Thrombolysis in STEMI :

Long Long-

• term Results

term Results

Keeley et al. Lancet 2003;361:13-20

Transfer PCI Transfer PCI

The DANAMI The DANAMI-

• 2 Trial

2 Trial

Danish Trial in Acute Myocardial Infarction-2

• Dr. Henning Rud Andersen

for the DANAMI-2 investigators

Danish Trial in Acute Myocardial Infarction Danish Trial in Acute Myocardial Infarction-

• 2

2

• Dr. Henning
• Dr. Henning Rud

Rud Andersen Andersen for the DANAMI for the DANAMI-

• 2 investigators

2 investigators

NEJM 2003, 349:733-742

14% 8% 0% 4% 8% 12% 16% 14% 8% 0% 4% 8% 12% 16%

Death / MI / Stroke (%) Death / MI / Stroke (%)

Lytic Lytic Primary PCI Primary PCI

P=0.0003 P=0.0003 P=0.002 P=0.002

Combined Combined Transfer Sites Transfer Sites

P=0.048 P=0.048

Non-Transfer Sites Non-Transfer Sites

DANAMI DANAMI-

• 2: Primary Results

2: Primary Results

RRR 45% RRR 45%

Lytic Lytic Primary PCI Primary PCI Lytic Lytic Primary PCI Primary PCI

14% 9% 0% 4% 8% 12% 16% 14% 9% 0% 4% 8% 12% 16% 12% 7% 0% 4% 8% 12% 16% 12% 7% 0% 4% 8% 12% 16%

RRR 40% RRR 40% RRR 45% RRR 45%

Captim Captim trial: trial:

Outcomes in patients randomized within first two Outcomes in patients randomized within first two hours of symptom onset hours of symptom onset

0.007 0.007 3.6 3.6 0.0 0.0 Cardiogenic shock (between Cardiogenic shock (between randomization and admission) randomization and admission) 0.032 0.032 5.3 5.3 1.3 1.3 Cardiogenic shock (between Cardiogenic shock (between randomization and discharge) randomization and discharge) 0.249 0.249 0.0 0.0 1.3 1.3 30 30-

• day stroke

day stroke 0.141 0.141 1.4 1.4 4.0 4.0 30 30-

• day reinfarction

day reinfarction 0.058 0.058 5.7 5.7 2.2 2.2 30 30-

• day death

day death 0.855 0.855 6.6 6.6 7.4 7.4 30 30-

• day death, reinfarction, or

day death, reinfarction, or stroke stroke p p Primary PCI Primary PCI <2 hours (%) <2 hours (%) Prehospital lysis Prehospital lysis <2 hours (%) <2 hours (%) End point End point Steg et al, Circulation 2003,108:2851

Peut Peut-

• on encore am
• n encore amé

éliorer les r liorer les ré ésultats sultats de l de l’ ’angioplastie coronaire ? angioplastie coronaire ?

F F-

• PTCA=Facilitated PCI

PTCA=Facilitated PCI

• PCI could be facilitated with :

PCI could be facilitated with :

• Thrombolysis (PACT, BRAVE, ASSENT 4,

Thrombolysis (PACT, BRAVE, ASSENT 4, FINESSE FINESSE… …) )

• GIIb/IIIa

GIIb/IIIa inhibitors (ADMIRAL, ON inhibitors (ADMIRAL, ON-

• TIME,

TIME, TIGER TIGER-

• PA, BRIDGING

PA, BRIDGING… …) )

Anti GP Anti GP IIb IIb-

• IIIa

IIIa F F-

• PTCA

PTCA

• ADMIRAL

ADMIRAL

• 300

300 pts pts

• Abciximab

Abciximab + stent vs stent + stent vs stent alone alone

• Combined

Combined end end-

• point

point ( (mortality mortality, , reinfarction reinfarction, revascularisation) , revascularisation) lower lower in in abciximab abciximab group group at at 30 30 days days: (6 vs 14.6%), : (6 vs 14.6%), and and at at six six months months (7.4 vs 15.9%) (7.4 vs 15.9%)

• TIMI 3

TIMI 3 flow flow before before angiogram angiogram : : 16.8 vs 5.4% 16.8 vs 5.4%

NEJM 2001; 341:1895-1903

59 % P=0,01 53 % P=0,02

Large AMI < 6hrs Large AMI < 6hrs Planned PCI Planned PCI Cath lab delay of 1 Cath lab delay of 1-

• 3 hr

3 hr

ASA ASA UFH (bolus) UFH (bolus) No lytic No lytic ASA ASA UFH (bolus) UFH (bolus) TNK TNK

Heparin as routinely used Heparin as routinely used NO NO GP IIb/IIIa inhibitors GP IIb/IIIa inhibitors Heparin as routinely used Heparin as routinely used GP IIb/IIIa inhibitors at GP IIb/IIIa inhibitors at investigators discretion investigators discretion

Angiography / PCI Angiography / PCI (immediate) (immediate) Angiography / PCI Angiography / PCI (immediate) (immediate)

n = 2,000 n = 2,000 n = 2,000 n = 2,000

Cath Cath lab lab

Stent / clopidogrel (optional) Stent / clopidogrel (optional) Stent / clopidogrel (optional) Stent / clopidogrel (optional)

Randomize Randomize

Thrombolysis F Thrombolysis F-

• PTCA

PTCA

van de Werf F. European Society of Cardiology Congress 2005; September 4-7, 2005; Stockholm, Sweden.

ASSENT 4 ASSENT 4 Pharmaco Pharmaco-

• Mechanical Reperfusion

Mechanical Reperfusion

0.04 0.04 32 (3.8) 32 (3.8) 50 (6.0) 50 (6.0) Number (%) of deaths Number (%) of deaths p p PCI alone PCI alone (n=838) (n=838) TNK+PCI TNK+PCI (n=828) (n=828) Outcome Outcome ASSENT ASSENT-

• 4: 30

4: 30-

• day mortality results

day mortality results

• The study was prematurely stopped because of a significant incre

The study was prematurely stopped because of a significant increase of death in the TNK group. ase of death in the TNK group.

AMI : ESC AMI : ESC recommendations recommendations

• PTCA

PTCA is is the the preferred preferred therapy therapy if : if :

• Artery

Artery can can be be opened

• pened in

in less less than than 90 minutes 90 minutes after after first first medical medical contact contact

• Contra

Contra-

• indications to

indications to thrombolytic thrombolytic therapy therapy

• Cardiogenic

Cardiogenic shock shock

• Thrombolytic

Thrombolytic therapy therapy in all in all other

• ther cases

cases

• Major

Major difficulties difficulties in in clinical clinical practice to practice to assess assess the the success success of

• f thrombolytic

thrombolytic therapy therapy based based on

• n

clinical clinical and and ECG data ECG data

• What

What should should be be done done if a if a coronary coronary angiogram angiogram is is performed performed immediately immediately after after thrombolytic thrombolytic therapy therapy ? ? Questions Questions raised raised by by thrombolytic thrombolytic therapy therapy: : The The Gray Areas Gray Areas

Angiographie de routine et angioplastie apr Angiographie de routine et angioplastie aprè ès s Thrombolyse ( Thrombolyse (Adjunctive Adjunctive PTCA) PTCA)

Adjunctive Adjunctive PTCA PTCA after after Thrombolytic Thrombolytic Therapy Therapy

• 3 trials

3 trials performed performed in in the the 80 80’ ’s s

• Topol

Topol et et al al (TAMI I), N (TAMI I), N Engl Engl J J Med Med 1987, 371; 581 1987, 371; 581-

• 8

8

• Simoons

Simoons et al et al Lancet Lancet 1988, 1; 197 1988, 1; 197-

• 203

203

• TIMI IIA

TIMI IIA study study, Circulation 1990; 81, 1457 , Circulation 1990; 81, 1457-

• 1476

1476

• Routine

Routine immediate immediate angiography angiography and and PTCA PTCA did did not not improve improve clinical clinical outcomes

• utcomes and

and was was associated associated with with increased increased bleeding bleeding and and a trend a trend towards towards increased increased mortality mortality

Adjunctive Adjunctive PTCA PTCA after after Thrombolytic Thrombolytic Therapy Therapy

• Patients treated with

Patients treated with thrombolytic thrombolytic therapy therapy have increased levels of platelet activation and have increased levels of platelet activation and aggregation aggregation

• These trials are old

These trials are old

• Would GP

Would GP IIb IIb-

• IIIa

IIIa antagonists help? antagonists help?

• Would

Would stenting stenting help? help?

Fernandes-Aviles et al, Lancet 2004;364 : 1045-53

GRACIA TRIAL

GRACIA Trial: GRACIA Trial:

Fernandes-Aviles et al, Lancet 2004;364 : 1045-53

No difference at 30 days

p=0.0008

Angioplasty after failure of Angioplasty after failure of thrombolysis thrombolysis (RESCUE) (RESCUE)

• Definition of failure of

Definition of failure of thrombolysis thrombolysis

• Detection of failure

Detection of failure

• Therapeutic options

Therapeutic options

• Re

Re thrombolysis thrombolysis

• Gp

Gp IIB IIIA IIB IIIA

• Rescue Angioplasty

Rescue Angioplasty

• Ballon

Ballon de de contrepulsion contrepulsion

TIMI Flow After TIMI Flow After Thrombolytic Thrombolytic Therapy Therapy

10 20 30 40 50 60 70 80 90 100 PAMI 1 GUSTO IIB t-PA SK TIMI 3 TIMI 2, 3

60 to 90 min after administration !!!!!

TIMI Flow After TIMI Flow After Thrombolytic Thrombolytic Therapy Therapy

• TIMI grade III

TIMI grade III patency patency is obtained in less than is obtained in less than 60% of patients 60% of patients

• We have probably reached the plateau

We have probably reached the plateau

• Adjunctive (

Adjunctive (antiplatelet antiplatelet ) medication provides ) medication provides little extra benefit, with excess adverse effects little extra benefit, with excess adverse effects due to the narrow therapeutic window of clot due to the narrow therapeutic window of clot lysis lysis versus bleeding risk versus bleeding risk

Diagnostic Diagnostic d d’é ’échec chec de thrombolyse de thrombolyse

• Douleur: difficile

Douleur: difficile à à quantifier quantifier

• Seule la s

Seule la sé édation totale de la douleur est un dation totale de la douleur est un bon signe pr bon signe pré édictif mais elle est trouv dictif mais elle est trouvé ée e seulement dans 29 % des art seulement dans 29 % des artè ères ouvertes res ouvertes

• Les analg

Les analgé ésiques peuvent masquer ce signe siques peuvent masquer ce signe

Electrocardiogramme Electrocardiogramme

Très spécifique pour prédire la perméabilité de l’artère

responsable de infarctus quand il y a une résolution complète (>70 %) du sus décalage du segment ST, mais ceci survient chez seulement une minorité de patients.

Chez la plupart des patients, il y a une résolution

partielle ou absence de résolution du sus décalage du segment ST, et l’état de perméabilité de l’artère responsable de l’infarctus est alors incertain.

Un chiffre seuil (cut off) de 50 % de résolution du

segment ST est un bon compromis

Rythme Idioventriculaire Accéléré

Enzymes et Enzymes et Marqueurs Marqueurs Biochimiques Biochimiques

• Cin

Ciné étique tique des enzymes : des enzymes :

• En

En faveur faveur d d’ ’un un é échec de thrombolyse: un chec de thrombolyse: un rapport rapport Troponin Troponin T, T, ou

• u CK

CK-

• MB mass,

MB mass, ou

• u

myoglobin myoglobin, par rapport au , par rapport au chiffre chiffre de base de base

• < 5

< 5 à à 60 60 mn mn

• < 10

< 10 à à 90 90 mn mn

• Sont

Sont surtout surtout r ré éserv servé és s pour pour une une confirmation confirmation post hoc, post hoc, plutôt plutôt que que comme comme aide au diagnostic aide au diagnostic imm immé édiat diat

Autres Autres outils

• utils diagnostiques

diagnostiques de de non reperfusion ? non reperfusion ?

• Scintigraphie

Scintigraphie: : Mais Mais besoin besoin d d’ ’obtenir

• btenir des

des images images avant avant la thrombolyse la thrombolyse

• Echographie

Echographie myocardiaque myocardiaque avec avec contraste contraste pour pour é évaluer valuer la perfusion la perfusion microvasculaire microvasculaire

Manque Manque de de m mé éthodes thodes non non invasives invasives fiables fiables pour pour d dé étecter tecter la reperfusion apr la reperfusion aprè ès s traitement traitement thrombolytique thrombolytique

• En

En Cons Consé équence quence, , une une coronarographie coronarographie en en urgence urgence est est souvent souvent n né écessaire cessaire pour pour d dé éterminer terminer la la perm permé éabilit abilité é de de l l’ ’art artè ère re coupable coupable, en , en particulier particulier en en cas cas d d’ ’infarctus infarctus ant anté érieur rieur ou

• u é

étendu tendu avec avec

• Douleur

Douleur thoracique thoracique persistante persistante

• Absence de

Absence de r ré ésolution solution du du sus sus d dé écalage calage du du segment ST segment ST

• Ou

Ou atteinte atteinte h hé émodynamique modynamique

• Persistant

Persistant plus de 90 min apr plus de 90 min aprè ès s traitement traitement thrombolytique thrombolytique. .

Que Que faire apr faire aprè ès s é échec de chec de thrombolyse? thrombolyse?

• Angioplastie

Angioplastie Evidemment Evidemment ? ?

Rescue Coronary Angioplasty

Meta-Analysis (small number of pts, non randomized studies)

Rescue Coronary Angioplasty Rescue Coronary Angioplasty

Meta Meta-

• Analysis

Analysis (small number of pts, non randomized studies)

(small number of pts, non randomized studies)

Pt Success Reocclusion Mortality (no.) (%) (%) (%) Topol 86 73 29 10.4 Califf 52 87 5 NR Belenkie 16 81 NR 6.7 Fung 13 92 16 7.6 Topol 22 86 3 0.0 Grines 12 100 8 NR Holmes 34 71 NR 11.0 Grines 10 90 12 10.0 O’Connor 90 89 14 17.0 Balm 37 92 26 5.4 Whitlow 44 84 28 NR Ellis 173 78 20 10.0 Total 560 451/560 69/380 10.6 (80%) (18%) Pt Pt Success Success Reocclusion Reocclusion Mortality Mortality (no.) (no.) (%) (%) (%) (%) (%) (%) Topol Topol 86 86 73 73 29 29 10.4 10.4 Califf Califf 52 52 87 87 5 5 NR NR Belenkie Belenkie 16 16 81 81 NR NR 6.7 6.7 Fung Fung 13 13 92 92 16 16 7.6 7.6 Topol Topol 22 22 86 86 3 3 0.0 0.0 Grines Grines 12 12 100 100 8 8 NR NR Holmes Holmes 34 34 71 71 NR NR 11.0 11.0 Grines Grines 10 10 90 90 12 12 10.0 10.0 O O’ ’Connor Connor 90 90 89 89 14 14 17.0 17.0 Balm Balm 37 37 92 92 26 26 5.4 5.4 Whitlow Whitlow 44 44 84 84 28 28 NR NR Ellis Ellis 173 173 78 78 20 20 10.0 10.0 Total Total 560 560 451/560 451/560 69/380 69/380 10.6 10.6 (80%) (80%) (18%) (18%)

Ellis SG et al: JACC 19:681 Ellis SG et al: JACC 19:681-

• 6, 1992

6, 1992

RESCUE Trial RESCUE Trial RESCUE Trial

Lytics to angiography 4.5±1.9 hr (mean) Lytics to angiography 4.5 Lytics to angiography 4.5± ±1.9 hr (mean) 1.9 hr (mean)

PTCA n=78 PTCA PTCA n=78 n=78 Anterior MI >2 mm ST ↑ IV thrombolytic therapy; Ongoing chest pain Coronary angiography 90 min − 8 hours from onset TIMI flow grade 0-1 Anterior MI Anterior MI > >2 mm ST 2 mm ST ↑ ↑ IV thrombolytic therapy; IV thrombolytic therapy; Ongoing chest pain Ongoing chest pain Coronary angiography 90 min Coronary angiography 90 min − − 8 hours from onset 8 hours from onset TIMI flow grade 0 TIMI flow grade 0-

• 1

1 Conservative strategy n=73 Conservative Conservative strategy strategy n=73 n=73

Excluded: Shock Prior MI Left main >50% Excluded: Excluded: Shock Shock Prior MI Prior MI Left main Left main > >50% 50%

Ellis SG et al: Circulation, 1994; 90:2280-84 Ellis SG et al: Circulation, 1994; 90:2280 Ellis SG et al: Circulation, 1994; 90:2280-

• 84

84

RESCUE : 30 days Results RESCUE : 30 days Results

39% 40% 38% 43% 35% 36% 37% 38% 39% 40% 41% 42% 43%

Resting LVEF Exercice LVEF

Conservative Angioplasty

Rescue Angioplasty in the Rescue Angioplasty in the setting of failed setting of failed thrombolysis seems to thrombolysis seems to improve exercise but not improve exercise but not rest ejection fraction rest ejection fraction

p=0.04

Ellis et al, Circulation 1994;90:2280-4

p=0.49

MERLIN Trial (The Middlesbrough Early Revascularization to Limit Infarction) MERLIN Trial MERLIN Trial ( (The

The Middlesbrough Middlesbrough Early Revascularization to Limit Infarction) Early Revascularization to Limit Infarction)

ST ST ↑ ↑ MI MI Lytic Tx Lytic Tx ≤ ≤10 hr 10 hr n=307 n=307 <50% reduction in ST <50% reduction in ST ↑ ↑ at 60 min at 60 min

Or, absence of accelerated Or, absence of accelerated idioventricular idioventricular rythm rythm

Continued Continued Medical Tx (n=154) Medical Tx (n=154) Rescue Rescue PCI (n=153) PCI (n=153)

1˚ endpoint: Death@30 days 1˚ endpoint: Death@30 days

Sutton AG et al, J Am Coll Cardiol 2004 Jul 21;44(2):287-96

MERLIN : 30 Days results MERLIN : 30 Days results

11 9,8 20,1 6,5 0,6 4,6 10,4 7,2 29,9 24,2 50 37,3

5 10 15 20 25 30 35 40 45 50

Death Revascularisation Stroke Re-MI CHF Composite

Conservative Rescue PCI

%

p<0.01 p=0.03 p=0.02

Sutton AG et al, J Am Coll Cardiol 2004 Jul 21;44(2):287-96

Raisons des Raisons des r ré ésultats sultats moins favorables de moins favorables de l l’ ’angioplastie apr angioplastie aprè ès s é échec de thrombolyse chec de thrombolyse

• D

Dé élais de diagnostic et de prise en charge lais de diagnostic et de prise en charge

• La thrombolyse entra

La thrombolyse entraî îne une activation plaquettaire. ne une activation plaquettaire.

• Les

Les é échecs de thrombolyse sont probablement associ checs de thrombolyse sont probablement associé és s à à des des plaques ath plaques athé éroscl rosclé éreuses plus complexes. reuses plus complexes.

• Dans un papier de

Dans un papier de Steffenino Steffenino ( (Ital Ital Heart Heart J 2004;5:739 J 2004;5:739-

• 745),

745), seulement 62% des seulement 62% des « « rescue rescue » » avaient un flux final TIMI grade 3. avaient un flux final TIMI grade 3.

• Même apr

Même aprè ès reperfusion s reperfusion é épicardique r picardique ré éussie (TIMI 3), la ussie (TIMI 3), la perfusion myocardique peut être d perfusion myocardique peut être dé éficiente ( ficiente (Embolisation Embolisation distale distale de de microthrombi microthrombi plaquettaires, plaquettaires, vasospasme vasospasme, inflammation, l , inflammation, lé ésions sions de reperfusion). Au maximum, No de reperfusion). Au maximum, No reflow reflow

• En plus, une angioplastie de sauvetage qui

En plus, une angioplastie de sauvetage qui é échoue comporte une choue comporte une mortalit mortalité é particuli particuliè èrement rement é élev levé ée. e.

Impaired Impaired microvascular microvascular reperfusion reperfusion (ST >or=to50%) (ST >or=to50%) despite despite successful successful mechanical mechanical recanalization recanalization

• according

according to age to age and and systolic systolic blood blood pressure (BP) on admission. pressure (BP) on admission.

Claeys Claeys: Circulation, Volume 1999, 99(15); 1972 : Circulation, Volume 1999, 99(15); 1972-

• 1977

1977

Comment Comment am amé éliorer liorer les les r ré ésultats sultats de l de l’ ’angioplastie de angioplastie de sauvetage sauvetage ? ?

• Inhibiteurs

Inhibiteurs de la de la Glycoprot Glycoproté éine ine II B II B-

• IIIA

IIIA ( (am amé éliorer liorer la perfusion la perfusion tissulaire tissulaire) )

• Stenting

Stenting ( (Stabiliser Stabiliser la la lumi lumiè ère re coronaire coronaire) )

REACT Trial

Gershlick A et al, AHA 2004

REACT Trial REACT Trial

Gershlick A et al, AHA 2004

ST ST ↑ ↑ MI MI Lytic tx Lytic tx ≤ ≤ 6 hr 6 hr n=427 n=427 >50% ST >50% ST ↑ ↑ on 90

• n 90-
• min ECG (w/ or w/o CP)

min ECG (w/ or w/o CP) PCI <12 hrs of sx onset PCI <12 hrs of sx onset Continued Continued Medical Tx Medical Tx n=200 n=200 Repeat Repeat Lytic Tx* Lytic Tx* n=200 n=200 Rescue Rescue PCI PCI n=200 n=200

1˚ endpoint: Death, re-MI, CVA, severe CHF, 6, 12 mo

Study terminated due to poor enrollment

1˚ endpoint: Death, re-MI, CVA, severe CHF, 6, 12 mo

Study terminated due to poor enrollment

*Fibrin specific; *Fibrin specific;

SK in 60%, RPA 27%, others 12%; Stents 88%, GP IIb/IIIa 55% SK in 60%, RPA 27%, others 12%; SK in 60%, RPA 27%, others 12%; Stents 88%, Stents 88%, GP IIb/IIIa 55% GP IIb/IIIa 55%

REACT: 6 month results REACT: 6 month results

31,0 15,3 29,8

5 10 15 20 25 30 35

%

31,0 15,3 29,8

5 10 15 20 25 30 35

%

Primary Composite Endpoint at 6 Months

(Death, MI, CVA, or severe heart failure)

Primary Composite Endpoint at 6 Months

(Death, MI, CVA, or severe heart failure)

• The primary composite endpoint of

death, MI, CVA or severe heart failure at 6 months was significantly lower in the rescue PCI group compared with either the repeat thrombolysis group or the conservative management group

• The primary composite endpoint of

death, MI, CVA or severe heart failure at 6 months was significantly lower in the rescue PCI group compared with either the repeat thrombolysis group or the conservative management group

Repeat Thrombolysis Repeat Thrombolysis Rescue PCI Rescue PCI Conservative Management Conservative Management p<0.001 p<0.001 p=0.002 p=0.002

Gershlick A et al, AHA 2004

Major Overt Bleeding Major Overt Bleeding

4,0 18,7 2,1

5 10 15 20

%

4,0 18,7 2,1

5 10 15 20

%

Repeat Thrombolysis Repeat Thrombolysis Rescue PCI Rescue PCI Conservative Management Conservative Management

Gershlick A et al, AHA 2004

Majority of bleeding was sheath complications

• The REACT results disagree with those of MERLIN trial,

The REACT results disagree with those of MERLIN trial, which showed no difference between rescue angiography and which showed no difference between rescue angiography and conservative treatment strategies at 30 days. conservative treatment strategies at 30 days.

• Hypotheses offered to explain the opposing outcomes of

Hypotheses offered to explain the opposing outcomes of MERLIN and REACT include : MERLIN and REACT include :

• differences in initial thrombolysis (

differences in initial thrombolysis (↑ ↑ streptokinase in streptokinase in MERLIN), MERLIN),

• concomitant medications (

concomitant medications (↑ ↑ GP IIb/IIIa inhibitors in GP IIb/IIIa inhibitors in REACT), REACT),

• and inclusion criteria (

and inclusion criteria (↑ ↑ time to rescue PCI in MERLIN) time to rescue PCI in MERLIN)

REACT: Summary REACT: Summary REACT: Summary

New technologies New technologies and and strategies strategies

• Distal protection

Distal protection during during PCI PCI

• Mechanical

Mechanical thrombectomy thrombectomy

• Endovascular

Endovascular cooling cooling system system

• Inhibition

Inhibition of

• f the

the complement complement

• Supersarturated

Supersarturated Oxygen Oxygen ( (Aqueous Aqueous Oxygen Oxygen) )

PTCA PTCA after after Thrombolytic Thrombolytic Therapy Therapy: Conclusions : Conclusions

• Successfull

Successfull reperfusion reperfusion after after thrombolytic thrombolytic therapy therapy

• 50

50-

• 60%

60%

• Non

Non-

• invasive

invasive methods methods to to assess assess reperfusion are reperfusion are lacking lacking

• Systematic

Systematic angiography angiography after after thrombolytic thrombolytic therapy therapy ? ?

• If

If the the coronary coronary artery artery is is occluded

• ccluded : RESCUE PTCA

: RESCUE PTCA is is justified justified

• If

If the the coronary coronary artery artery is is open :

• pen : Adjunctive

Adjunctive or

• r

Deferred Deferred PTCA? PTCA?

• The

The data are in apparent conflict data are in apparent conflict with with widespread widespread practice patterns !! practice patterns !!