Prehospital initiation of tirofiban in patients with ST-elevation myocardial infarction undergoing primary angioplasty (On-TIME 2): a multicentre, double-blind, randomised controlled trial.
BACKGROUND
The most effective magnitude and timing of antiplatelet therapy is important in patients with acute ST-elevation myocardial infarction (STEMI). We investigated whether the results of primary coronary angioplasty (PCI) can be improved by the early administration of the glycoprotein IIb/IIIa blocker tirofiban at first medical contact in the ambulance or referral centre.


METHODS
We undertook a double-blind, randomised, placebo-controlled trial in 24 centres in the Netherlands, Germany, and Belgium. Between June 29, 2006, and Nov 13, 2007, 984 patients with STEMI who were candidates to undergo PCI were randomly assigned to either high-bolus dose tirofiban (n=491) or placebo (N=493) in addition to aspirin (500 mg), heparin (5000 IU), and clopidogrel (600 mg). Randomisation was by blinded sealed kits with study drug, in blocks of four. The primary endpoint was the extent of residual ST-segment deviation 1 h after PCI. Analysis was by intention to treat. The trial is registered, number ISRCTN06195297.


RESULTS
936 (95%) patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. Median time from onset of symptoms to diagnosis was 76 min (IQR 35-150). Mean residual ST deviation before PCI (10.9 mm [SD 9.2] vs 12.1 mm [9.4], p=0.028) and 1 h after PCI (3.6 mm [4.6] vs 4.8 mm [6.3], p=0.003) was significantly lower in patients pretreated with high-bolus dose tirofiban than in those assigned to placebo. The rate of major bleeding did not differ significantly between the two groups (19 [4%] vs 14 [3%]; p=0.36).


CONCLUSIONS
Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI.
Van't Hof
Arnoud W J
AW
Isala Klinieken, Department of Cardiology, Zwolle, Netherlands.
Ten Berg
Jurriën
J
Heestermans
Ton
T
Dill
Thorsten
T
Funck
Reinhard C
RC
van Werkum
Wouter
W
Dambrink
Jan-Henk E
JH
Suryapranata
Harry
H
van Houwelingen
Gert
G
Ottervanger
Jan Paul
JP
Stella
Pieter
P
Giannitsis
Evangelos
E
Hamm
Christian
C
D015906:Angioplasty, Balloon, Coronary; D004311:Double-Blind Method; D004562:Electrocardiography; D004632:Emergency Medical Services / Q000379:methods* / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000628:therapy; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D000077466:Tirofiban; D016896:Treatment Outcome; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; D000077466:Tirofiban