Giving heart attack patients a high-dose of the anticlotting drug tirofiban in the ambulance before they reach hospital improves their clinical outcome. This is the conclusion of authors of an Article in this week's Cardiology Special Issue of The Lancet.
When patients have heart attacks, they can be classified in two ways, depending on the reading from the electrocardiogram (ECG). If the graph displays certain characteristics, the heart attack, or myocardial infarction, is termed an ST-elevated myocardial infarction (STEMI), whereas other heart attacks are classified as non-STEMI. For patients suffering STEMI, the dose and timing of antiplatelet (anticlotting) therapy they receive before primary coronary angioplasty* (PCI) is vital. Currently, a triple treatment package of aspirin, heparin, and clopidogrel is a standard therapy for STEMI patients in the ambulance. Dr Arnoud van't Hof, Isala Klinieken, Department of Cardiology, Zwolle, Netherlands, and colleagues did a randomised controlled trial (On-TIME 2) to investigate whether addition of the antiplatelet drug tirofiban to this standard package improved the results of PCI for these patients.
The study was carried out in 24 centres 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 (491 patients) or placebo (493) in addition to aspirin (500mg), heparin (5000IU) and clopidogrel (600mg). A total of 936 (95%) of these patients were randomly assigned to treatment after a prehospital diagnosis of myocardial infarction in the ambulance. The researchers found that ST deviation (a measure of the severity of the blockage affecting the heart) on the patients' electrocardiograms was significantly lower in the tirofiban group than the placebo group. Major bleeding did not differ significantly between the two groups, with 4% of patients in the tirofiban group and 3% in the placebo group suffering major bleeds.
The authors say: "Our 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…Our finding that routine prehospital initiation of high-bolus dose tirofiban improved ST-segment resolution and clinical outcome after PCI, emphasises that further platelet aggregation inhibition besides high-dose clopidogrel is mandated in patients with STEMI undergoing PCI."
In an accompanying Comment, Dr Gilles Montalescot, Institute of Cardiology Pitié-Salpêtrière Hospital, INSERM 856 and University of Paris 6, Paris, France, says: "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-organised hospital systems*** have been able to provide such a service."
Notes to editors:
*Primary coronary angioplasty- the method of opening the blocked artery with a balloon or stent
**High bolus dose: for better anti-clotting efficacy the bolus dose of Tirofiban was increased more than twice (previous studies had shown that a regular dose was not effective enough for getting optimal platelet aggregation inhibition)
***see figure in full Comment, p510
Dr Arnoud van't Hof, Isala Klinieken, Department of Cardiology, Zwolle, Netherlands T) +31 3842 44361 / +31 6506 35162 E) a.w.j.vant.hof@isala.nl
Dr Gilles Montalescot, Institute of Cardiology Pitié-Salpêtrière Hospital, INSERM 856 and University of Paris 6, Paris, France, contact by e-mail only E) gilles.montalescot@psl.aphp.fr
http://press.thelancet.com/ontime2.pdf
Journal
The Lancet