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Prehospital triple antiplatelet therapy in patients with acute ST elevation myocardial infarction leads to better platelet aggregation inhibition and clinical outcome than dual antiplatelet therapy
  1. Jaap Jan J Smit1,
  2. Jochem W van Werkum2,
  3. Jurrien ten Berg2,
  4. Robbert Slingerland3,
  5. Jan Paul Ottervanger1,
  6. Ton Heestermans4,
  7. Thorsten Dill5,
  8. Christian Hamm5,
  9. Arnoud W J van 't Hof1,
  10. on behalf of the Ongoing Tirofiban in Myocardial Infarction Evaluation (On-TIME) trial investigators
  1. 1Department of Cardiology, Isala Klinieken, Zwolle, The Netherlands
  2. 2Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands
  3. 3Department of Clinical Chemistry, Isala Klinieken, Zwolle, The Netherlands
  4. 4Department of Cardiology, Medisch Centrum Alkmaar, Alkmaar, The Netherlands
  5. 5Department of Cardiology, Kerckhoff-Klinik GmbH, Bad Nauheim, Germany
  1. Correspondence to Arnoud W J van 't Hof, Isala Klinieken, locatie Weezenlanden, Department of Cardiology, Groot Wezenland 20, 8011 JW Zwolle, The Netherlands; v.r.c.derks{at}


Objective To assess whether prehospital initiation of high-dose tirofiban in addition to high-dose clopidogrel results in more adequate inhibition of platelet aggregation (IPA) and better clinical outcome after primary percutaneous coronary intervention (PCI).

Methods Prespecified two-centre substudy of the prospective, international, multicentre, placebo controlled Ongoing Tirofiban in Myocardial Infarction Evaluation trial 2 (On-TIME-2 trial). 648 of 964 (67%) patients in the On-TIME-2 trial with ST elevation myocardial infarction undergoing primary PCI were studied. Pre-PCI IPA after early prehospital initiation of high-bolus dose (25 μg/kg) tirofiban was compared to placebo in addition to acetylsalicylic acid, unfractionated heparin and 600 mg clopidogrel.

Results IPA was measured at a median of 60 min after study medication administration. In all four tests: Fe induced platelet aggregation, ADP induced platelet aggregation, platelet function analyser (PFA)-100 (collagen–epinephrine and collagen–ADP cartridge) IPA was higher in patients pretreated with high-dose tirofiban (p<0.001 for all tests), even after >74 min of pretreatment. Patients in the highest quartile of IPA had less residual ST segment deviation 1 h post-PCI (p value for trend: p=0.001, 0.004, 0.001, 0.002 respectively). There was a significant relationship between PFA-100 (both cartridges) and major adverse cardiovascular events (MACE, p=0.028, p=0.035) and early thrombosis (p=0.009, p=0.007).

Conclusions 60 min of prehospital initiated antiplatelet treatment including high-dose tirofiban resulted in higher levels of IPA compared to pretreatment with acetylsalicylic acid and high-dose clopidogrel alone, even after longer pretreatment times. Levels of IPA were significantly related to ST resolution and MACE, including stent thrombosis. This substudy confirms the main findings of the On-TIME2 trial that clopidogrel alone is suboptimal, even at high dose and administered well in advance of primary PCI.

  • Platelet aggregation inhibition
  • platelet function
  • clinical outcome
  • tirofiban
  • platelets

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  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the Isala Klinieken Zwolle and St Antonius Hospital Nieuwegein, The Netherlands.

  • Provenance and peer review Not commissioned; externally peer reviewed.