Infarctus du myocarde : les questions et les r

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Infarctus du myocarde les questions et les
réponses

• C. Spaulding
• Cochin Hospital
• Rene Descartes University
• Paris, France

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Quelle est la méthode de réouverture la plus
efficace ?
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Once upon a time

• Thrombolytic therapy in AMI GUSTO trials
• PTCA in AMI the happy few

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PAMI and Zwolle trials

• PAMI trial
• NEJM 1993 328673-9
• Randomized comparison between t-PA and Primary
  angioplasty
• Zwolle trial
• NEJM 1993328680-84
• SK versus Primary PTCA

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PAMI trial

• rTPA vs Primary PTCA
• Exclusion criterias Contra-indications to
  thrombolytic therapy, cardiogenic shock
• Thrombolytic therapy t-PA
• PTCA 80-90
• 395 pts

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PAMI trial

• Mortality rate 6.5 vs 2.6 (p 0.06)
• High-risk patients(HRgt 100, gt 70 years, Anterior
  MI) 11 vs 2 (p0.01)
• Re-infarction 5 vs 13
• Bleeding 0 vs 2
• ANGIOPLASTY SUPERIOR TO t-PA, especially in
  high-risk patients

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Your trials are biased !!!!
Enough is enough !!
Here comes the interventional cardiologist !
A friendly discussion.
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Study limitations

• Fewer pts compared to thrombolytic therapy trials
• T-PA not the best regimen used
• SK out-dated
• High rate of bleeding complications in t-PA group

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And other studies less convincing

• Registries less or no difference
• Gusto II b NEJM, 1997,3361621-1628
• 1138 pts
• PTCA vs t-PA
• Death ou Reinfarction ou stroke 9.6 vs 13.7
  (p0.033)
• No difference at six months 14.1 vs 16.1

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DANAMI II

• PTCA versus in-hospital thrombolytic therapy
• Thrombolytic therapy performed either in
  hospitals with PTCA facilities or mostly in
  community hospitals with no PTCA facilities
• PTCA performed even if long transport delays
  (up to two hours)

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DANAMI II
Interval from onset of symptoms to admission
short, less than 2 hours
Long interhospital transportation delay 50 32
82 min
Time interval between hospital arrival and
angioplasty 26 min if transferred, 93 min if
admitted to hospital with PTCA facilities
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Meta-analysis

•  Primary angioplasty vs IV thrombolytic therapy
  for AMI a quantitative review of 23 randomised
  trials 
• Keeley EC, Boura JA, Grines CL
• Lancet, 4 janvier 2003

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Pre or In hospital thrombolytic therapy
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Peut-on améliorer les résultats de
langioplastie coronaire ?

• Stents
• GP II b III a platelet receptor antagonists

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Stents

• Non randomized studies
• Garcia E. et al Am J Cardiol 1996, 77451-454
• Spaulding et al Am J Cardiol  1997,
  791592-1595
• Saito et al J Am Coll Cardiol  1996, 2874-81
• Excellent in-hospital outcomes and low
  restenosis rates..

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Stents

• STENTIM
• French study 211 pts
• Wictor stent
• In-hospital complications no difference
• At six months less repeat PTCA
• 17.8 vs. 28.2

Work in progress Drug-Eluting Stents (Typhoon
et Horizon)
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GP II b III a Receptor Inhibitors

• ADMIRAL
• French study
• 300 pts
• Abciximab and stent vs stent alone
• At 30 days lower combined end-point (mortality
  rate,reinfarction, revascularisation) in
  abciximab group 6 vs 14.6, and at six months
  7.4 vs 15.9
• TIMI 3 flow before angiogram 16.8 vs 5.4

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Quand administrer les anti GP II b III a ?
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ADMIRAL - 1 Endpoint 30 days and 6 months
Circ 1999 100 (18) 1-86 abstract 439
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Primary PTCA

• Superior to Thrombolytic therapy
• In-hospital outcome improved by II B III A
  receptor inhibitors if administered before PTCA
• Six-month outcome improved by use of bare-metal
  stents
• Drug eluting stents Work in progress

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 Combination therapy with thrombolytic therapy
followed by adjunctive PTCA? 
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TIMI Flow After Reperfusion Therapy
60 to 90 min after administration !!!!!
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RESCUE PTCA
PTCA CONSERVATIVE P
30-d LVEF, Rest Excercise 40 /-11 43 /-15 39/-12 38/-13 .49 .04
30-d Outcome, (Death or CHF) 6.4 16.6 0.5
Ellis et al, Circulation 1994902280-4
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Adjunctive PTCA after Thrombolytic Therapy
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Adjunctive PTCA after Thrombolytic Therapy

• 3 trials performed in the 80s
• TIMI study group, N Engl J Med 1998 320, 618-627
• Topol et al, N Engl J Med 1987, 371 581-6
• Simoons et al Lancet 1998, 1 197-203
• No difference in two studies and increased
  mortality in one

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Combined pre-hospital thrombolysis with immediate
coronary angioplasty and stent
131 pts with AMI lt 12 hrs Pre-hospital
thrombolysis (mean 2 hrs) and immediate coronary
angioplasty independent of the infarct-artery
patency TIMI 3 flow 92 In-hospital mortality
4.6 Major bleeding 2.3 Intra-cranial hemorrhage
0.7 Re-infarction 2.3
Loubeyre et al. Eur Heart J 2001221128-35
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GRACIA TRIAL
Fernandes-Aviles et al, Lancet 2004364 1045-53
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GRACIA Trial
Fernandes-Aviles et al, Lancet 2004364 1045-53
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Repeat Thrombolytic Therapy or Rescue PTCA The
REACT Trial

• Patients treated by thrombolytic therapy with lt
  50 ST segment resolution
• Randomized to
• Repeat thrombolytic therapy
• Conservative therapy
• Rescue PTCA

Gershlick A et al, AHA 2004
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The REACT Trial

• Composite end-point (death, MI, stroke) at six
  months
• 31 in the lysis group
• 29.8 in the conservative group
• 15.3 in the PTCA group
• Angio performed 6 hours after thrombolytic
  therapy

Gershlick A et al, AHA 2004
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PTCA after Thrombolytic Therapy

• Successfull reperfusion after thrombolytic
  therapy
• 50-60
• Non-invasive methods to assess reperfusion are
  lacking
• Systematic angiography after thrombolytic therapy
  ?
• If the coronary artery is occluded RESCUE PTCA
  is justified
• If the coronary artery is open  adjunctive ,
   combination therapy  no randomized data

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ASSENT-4
Large AMI lt 6hrs intended PCI gt 60min
TNK UFH
UFH iv
Angio PCI IIb/IIIa forbidden (only BO)
Angio PCI IIb/IIIa not restricted
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Study Design
ST , high risk, lytic eligible, lt 12 h
UFH (40 U/kg (max 3000) 7 U/kg/h)
2 x 5 U bolus (30) Reteplase
Abciximab 0.25 mg/kg bolus 0.125 mg/kg/min x 12 h
(max 10 ?g/min)
IMMEDIATE PCI
MEDICAL TT RESCUE
Immediate Transfer to Cath Lab for PCI after PCI
remains in the hospital where PCI was performed
or is transferred back to referring hospital
CCU Admission Transfer for PCI only if
persistent ST elevation at 90 min (gt50 basal
ECG), chest pain or hemodynamic compromise
Death, Reinfarction, Refractory Ischemia at 30
Days
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FINESSE
STEMI / LBBB
60min delay
Transfer to the cath lab
Abciximab full dose half dose lytics
Abciximab full dose
Angio Primary PCI
Abciximab full dose after angio
FINESSE
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CAPTIM Can The French Do a Better Job ?
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PValue
PrehospitalThrombolysisn 419
PrimaryPCIn 421

• Primary endpoint () 8.2 6.2 0.29
• Death () 3.8 4.8 0.60
• Reinfarction () 3.7 1.7 0.13
• Disabling stroke () 1.0 0.0 0.12

RR 0.76 95 CI 0.46 - 1.24
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CAPTIM Pros and Cons

• Pros Pre-hospital thrombolytic therapy
• Cons study stopped with only 800 pts included,
  1200 planned (Public funding), local variations
  in PTCA procedures

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Impact of Time to Treatment on Mortality After
Prehospital Fibrinolysis or Primary Angioplasty
Data From the CAPTIM Trial

• Delaylt2 hours after symptom onset trend toward
  lower 30-day mortality with prehospital
  thrombolysis vs primary PCI (2.2 versus 5.7,
  P0.053)

Circulation. 20031082851
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Benefit of Thrombolysis According
toAdministration Delay
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PCIgtlytics quel que soit les délais
Délai symptôme-ttt n Mortalité J30 Lyse PCI Mortalité J30 Lyse PCI Différence absolue ()
0-60 747 6.0 4.7 1.3
gt60-120 2000 6.2 4.2 2.0
gt120-180 1852 7.3 5.5 1.8
gt180-360 1640 9.5 5.6 3.9
gt360 664 12.7 8.5 4.2
All patients 6903 7.9 5.4 2.5
0,64 (0.52-0.78)
Fibrinolyse meilleure
PCI meilleure
0.5
1.5
1
Boersma et al. AHA 2004
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Peut-on administrer des anti GP IIB IIIA chez un
patient thrombolysé ?
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Pourquoi ?
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No-reflow
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Occlusion dendoprothèse
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SPEED ASSENT 3 GUSTO V BRAVE
Pts 413 6095 16588 253
Traitement Reopro Reteplase vs Reteplase Tenecteplase Enox vs ½ Tenecteplase UFH Reopro vs Tenecteplase UFH Reteplase vs ½ Reteplase Reopro ½ Reteplase Reopro vs Reopro
Coro systématique Oui Non Non Oui
Efficacité Oui sur flux coronaire Oui Tenecteplase/enox ou ½ Tenecteplase UFH reopro Non Non
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SPEED STUDY ANGIO
TIMI 3 Flow (Median Time to Angiogram 62 Minutes)
Phase A
Phase B
A B
100
p0.001
p0.05
80
62
p0.39
61
54
51
60
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of Patients
40
27
20
n 98
n 48
n 60
n 100
n 90
n 70
0
-
5 U 5 U
Reteplase
5 U 5 U
5 U 5 U
5 U 5 U
Standard




-

Abx (B I)
60
60
40
60 40
70
60
UFH (U/kg)
Circulation 2000 101 2788-94
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ASSENT III - Large Scale Exploratory Trial
Primary Endpoints
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Thrombolyse Reopro vs. Reopro
SPEED
ASSENT 3
GUSTO V
BRAVE
9.8
P lt 0.001
NS
Reopro
5.6
Ass
4.6
4.4
3.7
2.3
2.2
1.6
Complications hemmoragiques
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•  Lassociation en routine des anti-GP II B IIIA
  et de la thrombolyse ne peut être recommandée. 

A distance (gt 3-4 heures) de la thrombolyse ?
Autres protocoles dassociation ?
Recommandations SEC, EHJ 2003 24 28-66
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AMI The Facts

• Primary PTCA is superior to thrombolytic therapy
• Primary PTCA should be performed using stents and
  II b III a receptor antagonists
• PTCA Round around the clock experienced team
  necessary, in-hospital delay 30-45 minutes to
  reopen the atery
• Thrombolytic therapy optimal in the first two
  hours after onset of chest pain (80-90), less
  after (average of 50-60)
• Maximal efficacy achieved 60 to 90 minutes after
  administration

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AMI The Facts

• Major difficulties in clinical practice to assess
  the success of thrombolytic therapy based on
  clinical and ECG data
• What should be done if a coronary angiogram is
  performed immediately after thrombolytic therapy
  ?

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AMI ESC recommendations

• PTCA is the preferred therapy if
• Artery can be opened in less than 90 minutes
  after first medical contact
• Contra-indications to thrombolytic therapy
• Cardiogenic shock
• Thrombolytic therapy in all other cases

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SAMU French Emergency Medical System
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Artery opened
18 min
Artery puncture
Pre-hospital and hospital delays in Paris (2003)
84 min
18 min
SAMU called
SAMU arrival
Hospital arrival
Pain onset
19 min
66 min
86 min
35 min
Thrombolytic Therapy
PTCA 36 min after hospital arrival
140 min
207 min ( 65 min)
All delays are means
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Acute Myocardial Infarction in Paris
AMI lt 6 hours, no CIND to thrombolytic therapy
Transportation delay lt45 min
Transportation delay gt 45 min
Aspirin sedation
Pre-hospital thrombolytic therapy
Gp2b3a Antagonists
85
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Cath lab
ICU
Joint decision by cardiologist and EMS physician
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AMI in Paris Exceptions

• Primary PTCA if contra-indications to
  thrombolytic therapy, no definite diagnosis,
  cardiogenic shock
• Thrombolytic therapy even if short tranportation
  delay if early administration ( first two hours
  after onset of chest pain) feasible

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AMI The Gray Areas

• Elderly (gt80 years of age) patients Primary
  PTCA or no reperfusion therapy ?
• Patients with pre-hospital thrombolytic therapy
• Coronary angiogram at admission ?
• Rescue PTCA if occluded artery
• Adjunctive PTCA if open artery ?

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Patients in  rural  areas

• Thrombolytic therapy is the preferred option
• No thrombolytic therapy and immediate transfer to
  center with interventional cardiology if
• Contra-indications to thrombolytic therapy
• Cardiogenic shock
• Secondary transfer if
• No evidence of reperfusion (ST segment elevation
  gt 50)
• Recurrent ischiemia
• Secondary cardiac failure/shock or mechanical
  complications
• Positive stress test performed before discharge

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The forgotten reperfusion patients
30 day death RR1.54
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In Conclusion

• Futur challenge reduce the number of patients
  without reperfusion therapy (thrombolytic therapy
  or PTCA)
• Treatment of AMI in a network is based on
  collaboration between pre-hospital medical teams
  and interventional cardiologists
• Pre-defined protocols
• Registries
• And

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Act like ducks !
On the water surface look calm and relaxed.

Under the water surface pedal like mad !!!