Giving heart attack patients a high-dose of the anti-clotting drug tirofiban in the ambulance before they reach the hospital improves their clinical outcome, according to the On-TIME trial published in the Aug. 19 cardiology special issue of The Lancet.
Currently, a triple treatment package of aspirin, heparin and clopidogrel (Plavix from Pfizer) is a standard therapy for STEMI patients in the ambulance. Arnoud van't Hof, MD, department of cardiology at Isala Klinieken in Zwolle, Netherlands, and colleagues conducted a randomized controlled trial (On-TIME 2) to investigate whether the addition of the antiplatelet drug tirofiban (Aggrastat from Merck and Medicure Pharma) to this standard package improved the results of PCI for these patients.
The study was carried out in 24 centers in the Netherlands, Germany and Belgium.
Between June 2006 and November 2007, 984 patients with STEMI, who were candidates to undergo PCI, were randomly assigned to either high-bolus dose tirofiban or placebo ,in addition to aspirin (500 mg), heparin (5000IU) and clopidogrel (600 mg), according to investigators. A total of 936 of these patients were randomly assigned to treatment after a pre-hospital diagnosis of MI in the ambulance.
Researchers found that ST deviation on the patients' ECGs was significantly lower in the tirofiban group than the placebo group. Major bleeding did not differ significantly between the two groups, with 4 percent of patients in the tirofiban group and 3 percent in the placebo group suffering major bleeds.
The authors said that their “trial was not powered on a difference in clinical outcome between the two groups. However, we noted a better clinical outcome in the tirofiban group than in the placebo group, with lower overall mortality and less urgent repeat PCI.”
This outcome emphasizes that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI, the authors wrote.
In an accompanying commentary, Gilles Montalescot, MD, from the Institute of Cardiology Pitié-Salpêtrière Hospital and the University of Paris, wrote: "On-TIME 2 tells us more than the benefit of high-dose tirofiban in pre-PCI. The study reveals that high-dose clopidogrel is not effective enough and confirms the needs for fast and strong platelet inhibition. It reminds us also that the first contact with the patient must be rapid and medical. Until now only well-organized hospital systems have been able to provide such a service."