Ongoing Tirofiban in Myocardial Infarction Evaluation Trial - ON-TIME
The goal of the trial was to evaluate the efficacy of early versus delayed tirofiban therapy in ST elevation myocardial infarction (STEMI) patients undergoing percutaneous coronary intervention (PCI).
Rates of thrombolysis in myocardial infarction (TIMI) grade 3 flow will be higher in the early tirofiban therapy arm compared with the late therapy arm in STEMI patients.
Patients Enrolled: 507
Mean Follow Up: 30 days
Mean Patient Age: Mean age 62 years
Chest pain >30 minutes with STEMI
TIMI flow grade 3 at initial angiography
At initial angiography: TIMI flow grade 0, 1, 2, and 3; TIMI frame count; myocardial blush grade; thrombus; and PCI success
Patients with acute MI were randomized in the ambulance or referral center to early tirofiban therapy (n=251) or later tirofiban therapy in the catheterization lab (n=256).
"Early therapy" consisted of tirofiban in the ambulance or referral center (10 µg/kg/bolus + 0.15 µg/kg/min infusion) followed by transport to the treatment center and angiography with a blinded placebo tirofiban bolus.
"Late therapy" consisted of placebo bolus followed by transport to the treatment center and angiography with tirofiban bolus. All patients were treated with a 24-hour tirofiban infusion following catheterization.
Unfractionated heparin (5000 IU) and aspirin (500 mg intravenously); post-percutaneous coronary intervention (PCI) clopidogrel was administered (300 mg immediately + 75 mg/day).
Randomization occurred in the ambulance in 41% of patients. PCI was performed in 89% of patients. In the early therapy arm, tirofiban therapy was administered a mean of 59 minutes earlier than in the late therapy arm.
There was no difference between treatment arms in the primary endpoint of TIMI grade 3 flow (19% early vs. 15% late, p=0.22), but patency (TIMI 2 or 3 flow) occurred more frequently in the early tirofiban arm (43% vs. 34%, p=0.04). Thrombus was present less often in the early tirofiban arm (25% vs. 32%, p=0.06). There was no difference in post-PCI TIMI flow grade 3 (89% vs. 91%), TIMI frame count (27 vs. 26 frames), or myocardial blush grade 3 (51% vs. 53%).
All subgroups favored the early tirofiban arm for the endpoint of TIMI flow grade 2/3. Rates of 30-day clinical endpoints were relatively low: death 2.2%, recurrent MI 1.0%, stroke 0.2%, and major bleed 3.7%. There was no difference in one-year death (4.5% vs. 3.7%, p=0.66), reinfarction (2.4% vs. 3.7%, p=0.43), or the composite of death or MI (7.0% each, p=1.0) for the early and late groups, respectively.
Among STEMI patients undergoing PCI, early administration of tirofiban therapy was not associated with a difference in the primary endpoint of TIMI flow grade 3 compared with cath lab administration of tirofiban, but early therapy was associated with an increase in patency (TIMI flow grade 2/3) and a lower rate of thrombus.
While the primary endpoint did not differ significantly, early patency may be a more clinically important endpoint since 89% of patients underwent PCI, and the time from hospital arrival to PCI was relatively short. The short time to PCI may have contributed to the low 30-day event rates.
van 't Hof AW, Ernst N, de Boer MJ, et al. Facilitation of primary coronary angioplasty by early start of a glycoprotein 2b/3a inhibitor: results of the ongoing tirofiban in myocardial infarction evaluation (On-TIME) trial. Eur Heart J. 2004 May;25(10):837-46.
Presented at the American College of Cardiology Scientific Session, March 2004.
Presented by A.W.J. Van't Hof at the European Society of Cardiology Congress, Vienna, Austria, September 2003.
Presented at Late-breaking Clinical Trials, Transcatheter Cardiovascular Therapeutics 2003, Washington, DC.
Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Prevention
Keywords: Stroke, Myocardial Infarction, Platelet Aggregation Inhibitors, Referral and Consultation, Fibrinolytic Agents, Angioplasty, Balloon, Coronary, Tyrosine, Secondary Prevention, Thrombosis, Chest Pain, Catheterization, Platelet Glycoprotein GPIIb-IIIa Complex
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