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Ongoing Tirofiban in Myocardial Infarction Evaluation Trial - ON-TIME
Description:
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).
Hypothesis:
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.
Study Design
Patients Enrolled: 507
Mean Follow Up: 30 days
Mean Patient Age: Mean age 62 years
Female: 20%
Patient Populations:
Chest pain >30 minutes with STEMI
Primary Endpoints:
TIMI flow grade 3 at initial angiography
Secondary Endpoints:
At initial angiography: TIMI flow grade 0, 1, 2, and 3; TIMI frame count; myocardial blush grade; thrombus; and PCI success
Drug/Procedures Used:
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.
Concomitant Medications:
Unfractionated heparin (5000 IU) and aspirin (500 mg intravenously); post-percutaneous coronary intervention (PCI) clopidogrel was administered (300 mg immediately + 75 mg/day).
Principal Findings:
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.
Interpretation:
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.
References:
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.
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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