Prehospital Fibrinolysis with Double Antiplatelet Therapy in Acute ST-Elevation Myocardial Infarction:

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Prehospital Fibrinolysis with Double Antiplatelet
Therapy in Acute ST-Elevation Myocardial
Infarction The Clarity Ambulance Substudy
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Ambulance Substudy Background

• Fibrinolysis for ST-elevation acute myocardial
  infarction (STEMI) is frequently limited by
  delays of administration as well as incomplete
  reperfusion or reocclusion of the infarct-related
  artery1
• Intensified prehospital management may shorten
  time to treatment and improve outcomes2

1. Brouwer MA et al. Circulation 2002 106
659665. 2. Morrison LJ et al. JAMA 2000 283
26862692.
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Substudy Sites and Patient Numbers

• France 172 patients
• L Soulat 57
• Y Lambert 48
• F Lapostolle 28
• F Thieuleux 21
• C Gully 10
• D Pollet 5
• D Galley 2
• L Olliver 1

UK 40 patients J Adgey 27 J Purvis 13 Sweden
5 patients J-E Karlsson 5
217 patients in total
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Baseline Characteristics Ambulance vs.
Non-Ambulance
Characteristic Ambulance (n216) Non-ambulance (n3275)
Age (years, mean ? SD) 57 ? 11 58 ? 10
Male () 81 80
Hypertension () 35 35
Dyslipidaemia () 36 32
Current smoker () 49 50
Diabetes () 13 17
Prior MI () 10 9
Anterior MI () 41 41
Fibrin-specific lytic () 100 67
Betablockers () 86 89
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Patient Management Ambulance vs. Non-Ambulance
Patient management Ambulance (n216) Non-ambulance (n3275)
Symptom onset to randomization (hours) 1.9 2.8
Symptom onset to fibrinolytic (hours) 1.9 2.8
Total duration of ischaemic symptoms (hours, mean ? SD ) 3.7 ? 2.4 5.1 ? 5.3
Fibrinolytic to study drug (min) 10 10
Time to angiography (hours) 68 87
p lt0.001 versus ambulance patients values are
median unless otherwise specified
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Angiographic ECG Parameters Ambulance vs.
Non-Ambulance
Event rate ()
Odds ratio (95 CI)
p value
Ambulance
Non-ambulance
TFG 3 64.4 64.4 NS
Complete ST resolution at ECG 90 min 180 min 47.2 63.2 37.0 52.7 0.02 0.05
Ambulance better
Non-ambulance better
Complete considered to be gt70
ECGelectrocardiogram
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Primary Outcome Parameters Ambulance vs.
Non-Ambulance
Event rate ()
Odds ratio (95 CI)
p value
Ambulance
Non-ambulance
Primary efficacy endpoint 21.8 18.1 NS
TFG 0/1 17.1 14.9 NS
30-day clinical outcome Cardiovascular death Re-MI Re-ischaemia urgingrevascularization Overall 4.6 7.4 2.3 13.4 4.4 4.8 4.1 12.9 NS NS 0.05 NS
Non-ambulance better
Ambulance better
Occluded infarct artery (TFG 0/1) death
re-MI prior to angiography NSnot significant
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Baseline Characteristics Ambulance Subgroup
Characteristic Clopidogrel (n109) Placebo (n107)
Age (years ? SD) 57 ? 10 56 ? 12
Male () 80 81
Hypertension () 33 36
Dyslipidaemia () 33 39
Current smoker () 54 43
Diabetes () 12 15
Prior MI () 8 11
Anterior MI () 35 48
Fibrin-specific lytic () 100 99
Betablockers () 85 88
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Primary Outcome Parameters Ambulance Subgroup
Event rate ()
Odds ratio (95 CI)
p value
Clopidogrel
Placebo
Primary efficacy endpoint 16.5 27.1 0.06
TFG 0/1 11.8 22.3 0.05
30-day clinical outcome Cardiovascular death Re-MI Re-ischaemia urgingrevascularization Overall 5.5 5.5 1.8 12.8 3.7 9.3 2.8 14.0 NS NS NS NS
Placebo better
Clopidogrel better
Occluded infarct artery (TFG 0/1) death
re-MI prior to angiography
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Primary Endpoint of TIMI Flow Grade 0/1, MI or
Death
Odds ratio (95 CI)
0.60 (0.30?1.17)
Ambulance
0.65 (0.54?0.77)
Non-ambulance
Overall
0.64 (0.53?0.76)
0
0.5
1.0
1.5
2.0
Clopidogrel better
Placebo better
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Safety Bleeding Complications
Bleeding complications Event rates () Event rates () p value
Ambulance Non-ambulance
TIMI major bleeding by day after angiography 1.0 1.2 NS
ICH 1.0 0.6 NS
TIMI major bleeding by 30 days 3.4 1.7 NS
Clopidogrel Placebo
TIMI major bleeding by day after angiography 0 1.9 ?
ICH 0 1.9 ?
TIMI major bleeding by 30 days 1.9 4.9 NS
TIMIthrombolysis in myocardial infarction
ICHintracranial hemorrhage
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Conclusions

• Medical reperfusion of STEMI patients with
  fibrinolysis, heparin, ASA and clopidogrel is
  feasible before reaching the hospital in
  medically equipped ambulances without an apparent
  increase in bleeding
• Early management of patients in the ambulance is
  associated with shorter ischaemic times and
  faster reperfusion, with a consistent treatment
  effect in favour of clopidogrel in comparison
  with the overall results