High dose tirofiban and clopidogrel are safe and effective in the ON-TIME-2 trial

April 1, 2008 By Vijayalakshmi Kunadian MBBS MD MRCP [mailto:vkunadian@perfuse.org]

 SCAI-ACCi2 08-Chicago, IL: The ON-TIME-2 investigators have reported that the early (pre-hospital or at referral center) administration of high dose tirofiban together with 600 mg of clopidogrel is safe and effective among patients with acute ST segment elevation myocardial infarction undergoing primary PCI. The results were presented by Dr Christian Hamm at the SCAI Annual Scientific Sessions in partnership with ACC i2 summit late breaking abstract sessions on April 1, 2008 in Chicago.

The ON-TIME-1 trial (ONgoing Tirofiban In Myocardial Infarction Evaluation) demonstrated that there was no benefit using low dose tirofiban in the setting of an acute myocardial infarction. The ON-TIME-2 registry evaluated the use of high dose tirofiban in 416 patients. The ON-TIME-2 trial is a randomized, double blind, placebo-controlled trial using early (pre-hospital, in the ambulance/ in the referral hospital) high dose tirofiban (25μg/kg followed by 0.5μg/kg/minute infusion) versus placebo in 984 patients with ST elevation myocardial infarction from June 2006 to November 2007 from 3 countries (Holland, Germany and Belgium). All patients received aspirin, 600 mg of clopidogrel and unfractionated heparin in the ambulance or in the referral centers.

The primary endpoint of this study was the residual ST segment deviation (>3 mm) one hour after primary percutaneous coronary intervention (PCI). The secondary endpoint was the composite of death, recurrent myocardial infarction, urgent target vessel revascularization, stroke, or thrombotic bail-out at 30 days follow-up. The safety endpoint was major bleeding.

There were no significant differences in the baseline characteristics between the placebo group (n=493) and the tirofiban group (n=491). Around 95% of patients were admitted directly from the ambulance, 3% were transferred from referral centers and 2% from the PCI centers. PCI was performed in 90% of cases in the placebo group and 87.6% of cases in the tirofiban group (p=0.235).

The primary endpoint of persistent ST elevation > 3 mm was observed in 44.3% and 36.6% of cases in the placebo and tirofiban groups respectively (p=0.026).

The absolute mm of residual ST segment deviation was also significantly improved in the tirofiban group compared with the placebo group prior to PCI (10.9 ± 9.2 mm vs. 12.1 ± 9.4 mm, p=0.028), at 60 minutes (4.4 ± 5.3 mm vs. 5.9 ± 8.1 mm, p=0.022) and at 90 minutes (3.3 ± 4.3 mm vs. 4.8 ± 6.3 mm, p=0.002).

The combined secondary endpoint was significantly reduced in the tirofiban group compared with the placebo group (26% vs. 33.3%, p=0.013). Thrombotic bailout (19.9% vs. 28.5%, p=0.002) and abrupt closure (0.2% vs. 2.2%, p=0.004) was significantly reduced in the tirofiban group. There was no significant difference in the occurrence of either major bleeding (placebo: 2.9% vs. tirofiban: 4%, p=0.363) or minor bleeding (placebo: 4.4% vs. tirofiban: 6.1%, p=0.233) between the two groups.

The investigators concluded that among patients with ST elevation myocardial infarction, the referring hospital or pre-hospital use of high dose tirofiban along with high loading dose clopidogrel is safe and effective.

Source
Late Breaking Abstracts Session: SCAI Annual Scientific Sessions in partnership with ACC i2 summit, April 1, 2008 Chicago