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Original research article
Long-term mortality and prehospital tirofiban treatment in patients with ST elevation myocardial infarction
  1. Enrico Fabris1,2,
  2. Sinem Kilic1,
  3. Dirk A A M Schellings3,
  4. Jurrien M ten Berg4,
  5. Mark W Kennedy1,
  6. K Gerts van Houwelingen5,
  7. Evangelos Giannitsis6,
  8. Evelien Kolkman7,
  9. Jan Paul Ottervanger1,
  10. Christian Hamm8,
  11. Arnoud W J van’t Hof1,9
  1. 1 Department of Cardiology, Isala Klinieken, Zwolle, The Netherlands
  2. 2 Cardiovascular Department, University of Trieste, Trieste, Italy
  3. 3 Slingeland Ziekenhuis, Doetinchem, The Netherlands
  4. 4 Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands
  5. 5 Cardiology Department, Thoraxcentrum Twente, Medisch Spectrum Twente, Enschede, The Netherlands
  6. 6 Department of Cardiology, Universitats Klinik, Heidelberg, Germany
  7. 7 Diagram CRO, Zwolle, The Netherlands
  8. 8 Department of Cardiology, Kerckhoff Klinik, Bad Nauheim, Germany
  9. 9 Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands
  1. Correspondence to Professor Arnoud W J van’t Hof, Department of Cardiology, Maastricht University Medical Center, Maastricht, The Netherlands; awjhof{at}


Objective We undertook a subgroup analysis of the On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2), a placebo-controlled, double-blind, randomised trial, in order to evaluate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels and long-term (5 years) mortality and to investigate the effect of prehospital tirofiban administration on mortality in relation to NT-proBNP levels.

Methods A total of 984 patients with ST elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) were randomised to either in ambulance tirofiban or placebo. NT-proBNP levels were evaluated on admission before angiography (baseline) and 18–96 hours thereafter (post PCI).

Results There were 918 (93.3%) patients with NT-proBNP values available at baseline and 865 (87.9%) post PCI. Patients with baseline NT-proBNP values above the median (137 pg/mL) had higher 30-day (5.1% vs 0.2%, p<0.001), 1-year (7.0% vs 0.7%, p<0.001) and 5-year (20.3% vs 4.9%, p<0.001) mortality as compared with patients with values below the median. Using multivariate Cox analysis, NT-proBNP above the median was an independent predictor for 5-year mortality (HR 2.73, 95% CI 1.47 to 5.06; p=0.002). Patients with values above the median who received early tirofiban treatment had significant lower mortality compared with patients treated with placebo at 30 days (2.7% vs 7.5%, p=0.021) and 1 year (4.5% vs 9.4%, p=0.043). At 5 years, a lower but non-significant mortality rate was maintained in the treatment group (18% vs 22.4%, p=0.265).

Conclusions In patients with STEMI, baseline NT-proBNP level independently predicts long-term mortality. In patients with baseline NT-proBNP levels above the median, early prehospital treatment with tirofiban significantly reduced 30-day and 1-year mortality, suggesting that high-risk patients may derive particular benefit. This finding should be confirmed in other studies.

Trial registration number ISRCTN06195297.

  • Glycoprotein IIb/IIIa inhibitors
  • tirofiban
  • NT-proBNP
  • long-term mortality.

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  • Contributors All authors have contributed significantly to the paper, in particular: EF, AWJVH: conception and design of the paper; EF, SK, MWK, AWJVH: drafting of the manuscript; EK: provided statistical expertise and analysis of data; DAS, JMTB, KGVH, EG, JPO, CH: revising critically the manuscript for important intellectual content.

  • Competing interests None declared.

  • Ethics approval The On-Time 2 trial was approved by the central Medical Ethics Review Committee (METC) of the Isala Ziekenhuizen of Zwolle (Netherlands) and by all local ethics committees involved.

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