ONTIME2 OngoingTirofiban In Myocardial Infarction Evaluation

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ON-TIME-2Ongoing-Tirofiban In MyocardialInfarcti
on Evaluation

• The On-TIME 2 investigators

See last slide
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Aim

• Class 2A indication
• Registries 2b/3a in only 25-30
• No evidence in pts pre-treated with HD
  Clopidogrel
• Timing of 2b/3a?

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Acute myocardial infarction diagnosed in
ambulance or referral center ASA600 mg
clopidogrel
Tirofiban
Placebo
Transportation
Angiogram
Angiogram
PCI centre
Tirofiban provisional
Tirofiban contd
PCI
Bolus 25 µg/kg 0.15 µg/kg/min infusion
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Trial Design(Registration ISRCTN 06195297)
Multicenter, prospective, randomized,
international Analysis ITT ECG and Angio Core
Lab End-points adjudicated (CEC) Investigator
initiated and driven Unrestricted grant from
Merck Co Inc.
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• Inclusion Criteria
• Chest pain gt 30 min but less than 24 hours
• ST ? in 2 contiguous leads gt 0.2 mV (anterior
  MI) or 0.1 mV (non-anterior MI)

• Exclusion Criteria
• Age gt 85 yrs
• Women lt 50 yrs
• Lytic therapy lt 24 hrs
• Acenocoumarol lt 7 days
• CI to 2b/3a blockade
• Killip IV
• Hemodialysis

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Study Phases

• Open Label
• June 2004 June 2006
• N414
• 2 centres
• Netherlands
• HBD tirofiban or no tirofiban
• 600 mg clopidogrel, heparin, ASA

• Double Blind
• June 2006 Nov 2007
• N984
• 24 centres
• Netherlands, Germany, Belgium
• HBD tirofiban or placebo
• 600 mg clopidogrel, heparin, ASA

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Double Blind Phase

• further platelet aggregation inhibition besides
  high-dose
• clopidogrel improves ST resolution both before
  and after PCI

On-TIME 2 study. Lancet. 2008372537-46.
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Baseline Data
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Ischemic Time
39 within Golden Hour
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Residual ST-Deviation After PCI
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Initial TIMI Flow
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Pooled AnalysisOpen Label and Double Blind
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Pooled AnalysisResidual ST-Deviation After PCI
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Complete ST-Resolution Before PCI
ECG Diagnosis in Ambu 11.00 hrs
ECG Arrival PCI Centre 11.40 hrs
Tirofiban 19.0 No Tirofiban 14.6 P0.049
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Effect on Different End Points
Surrogate End Points
Clinical End Points
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Survival Free from MACE
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Residual ST-Deviation and Mortality
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Total Mortality
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Why in Ambulance?
Surrogate End Points
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Why in Ambulance?
Clinical End Points
Pain-diagnosis lt 75 min
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Summary

• Effect of pre-hospital tirofiban (HDB) on initial
  TIMI flow and ST resolution evident in 2 separate
  study phases
• Pooled analysis more aborted infarction and
  reduced incidence of MACE and total mortality
• No significant increase in major bleeding
• Highest efficacy when (HBD) tirofiban is given
  early after symptom onset

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Conclusion

• Do not wait with 2b/3a until arrival in the
  cath-lab!

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Participating Centers

• The Netherlands
• 1. Isala klinieken Zwolle Dr AWJ van t Hof
• 2. Antonius Ziekenhuis Nieuwegein Dr J ten Berg
• 3. UMC Utrecht Drs PR Stella
• 4. Medisch Spectrum Twente Dr K van Houwelingen
• Germany
• 1. Kerckhoff-Klinik Prof Dr C Hamm
• 2. Universitätsklinikum Heidelberg Prof Dr H
  Katus
• 3. St. Johannes Hospital Dortmund Prof Dr Heuer