Effect of early, pre-hospital initiation of high bolus dose tirofiban in patients with ST-segment elevation myocardial infarction on short- and long-term clinical outcome.
OBJECTIVE
The purpose of this trial was to study the effect of a high bolus dose (HBD) of tirofiban on clinical outcome in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI).


BACKGROUND
The On-TIME 2 (Ongoing Tirofiban In Myocardial infarction Evaluation 2) placebo-controlled, double-blind, randomized trial showed that early administration of HBD tirofiban in the ambulance improves ST-segment resolution in patients with STEMI undergoing primary percutaneous coronary intervention. The effect of early tirofiban treatment on clinical outcome is unclear.


METHODS
The On-TIME 2 trial consisted of 2 phases: an open-label phase, followed by a double-blind, placebo-controlled phase. STEMI patients were randomized to either HBD tirofiban or no tirofiban (phase 1) or placebo (phase 2) in addition to aspirin, heparin, and high-dose clopidogrel. The protocol pre-specified a pooled analysis of the 2 study phases to assess the incidence of major adverse cardiac events at the 30-day follow-up and on total mortality at the 1-year follow-up.


RESULTS
During a 3-year period, 1,398 patients were randomized, 414 in phase 1 and 984 in phase 2. Major adverse cardiac events at 30 days were significantly reduced (5.8% vs. 8.6%, p = 0.043). There was a strong trend toward a decrease in mortality (2.2% vs. 4.1%, p = 0.051) in patients who were randomized to tirofiban pre-treatment, which was maintained during the 1-year follow-up (3.7% vs. 5.8%, p = 0.08). No clinically relevant difference in bleeding was observed.


CONCLUSIONS
Early, pre-hospital initiation of HBD tirofiban, in addition to high-dose clopidogrel, improves the clinical outcome after primary percutaneous coronary intervention in patients with STEMI. (Ongoing 2b/3a inhibition In Myocardial infarction Evaluation; ISRCTN06195297).
St Antonius Hospital, Nieuwegein, the Netherlands.
Jurriën M
JM
ten Berg
Arnoud W J
AW
van 't Hof
Thorsten
T
Dill
Ton
T
Heestermans
Jochem W
JW
van Werkum
Arend
A
Mosterd
Gert
G
van Houwelingen
Petra C
PC
Koopmans
Pieter R
PR
Stella
Eric
E
Boersma
Christian
C
Hamm
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015906:Angioplasty, Balloon, Coronary / Q000379:methods / Q000401:mortality; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004562:Electrocardiography; D004632:Emergency Medical Services / Q000379:methods*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D020551:Pulse Therapy, Drug; D012016:Reference Values; D018570:Risk Assessment; D016037:Single-Blind Method; D016019:Survival Analysis; D013997:Time Factors; D000077466:Tirofiban; D016896:Treatment Outcome; D014443:Tyrosine / Q000008:administration & dosage / Q000031:analogs & derivatives*
D010975:Platelet Aggregation Inhibitors; D014443:Tyrosine; D000077466:Tirofiban