title: Higher efficacy of pre-hospital tirofiban with longer pre-treatment time to primary PCI: protection for the negative impact of time delay.
abstract: OBJECTIVE
  To evaluate the impact of longer duration of pre-hospital initiated antiplatelet and antithrombotic therapy on outcome in patients with ST-segment elevation myocardial infarction (STEMI).
  
  
  RESULTS
  In this sub-analysis of the Ongoing Tirofiban in Myocardial Evaluation (On-TIME) 2 trial, we studied, in 1,370 patients, the effect of pre-treatment time (time from administering study medication to time of angiography) on complete ST-segment resolution (STR), initial patency and 30-day mortality. Study medication consisted of high dose tirofiban (HDT) or control (placebo or no HDT) on top of high dose clopidogrel, aspirin and unfractionated heparin. Median pre-treatment time was 55 min (44-70). Longer pre-treatment was associated with longer transportation times, longer in-hospital delay, longer total ischaemic time (all p<0.001) and higher 30-day mortality (3.6% vs. 1.8%, p=0.046). Longer HDT pre-treatment time was independently associated with increased complete STR both before (odds ratio [OR] 1.51, 95%; confidence interval [CI] 0.98-2.32; p=0.06) and after PCI (OR 1.43, 95%; CI 1.02-2.02; p=0.039) and with a significantly improved initial TIMI 2 or 3 flow (51.4% vs. 43.4%, p=0.042) and reduced 30-day mortality (2.1% vs. 5.0%, p=0.047) as compared to longer control pre-treatment.
  
  
  CONCLUSIONS
  Longer time delay before primary PCI is associated with increased mortality. Pre-treatment with high dose tirofiban, however, may compensate for this negative effect by improving ST-segment resolution and initial patency and by reducing mortality. Further studies should be performed to confirm that this is an attractive therapy for patients with longer delays to reperfusion.
authors.affiliation: Department of Cardiology, Medisch Centrum Alkmaar, Alkmaar, The Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: Heestermans
authors.forename: Menko-Jan
authors.initials: MJ
authors.lastname: de Boer
authors.forename: Jochem W
authors.initials: JW
authors.lastname: van Werkum
authors.forename: Arend
authors.initials: A
authors.lastname: Mosterd
authors.forename: A T Marcel
authors.initials: AT
authors.lastname: Gosselink
authors.forename: Jan-Henk E
authors.initials: JH
authors.lastname: Dambrink
authors.forename: Gert
authors.initials: G
authors.lastname: van Houwelingen
authors.forename: Petra
authors.initials: P
authors.lastname: Koopmans
authors.forename: Christian
authors.initials: C
authors.lastname: Hamm
authors.forename: Felix
authors.initials: F
authors.lastname: Zijlstra
authors.forename: Jurriën M
authors.initials: JM
authors.lastname: ten Berg
authors.forename: Arnoud W J
authors.initials: AW
authors.lastname: van 't Hof
mesh_terms: D000368:Aged; D000552:Ambulances; D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000401:mortality; D001241:Aspirin / Q000008:administration & dosage; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D017023:Coronary Angiography; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004632:Emergency Medical Services; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006297:Health Services Accessibility; D006493:Heparin / Q000008:administration & dosage; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D009426:Netherlands; D010043:Outcome and Process Assessment, Health Care; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D013997:Time Factors; D000077466:Tirofiban; D016896:Treatment Outcome; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; D006493:Heparin; D000077144:Clopidogrel; D000077466:Tirofiban; D013988:Ticlopidine; D001241:Aspirin