Indexed on: 01 Jan '06Published on: 01 Jan '06Published in: Future cardiology
Platelet activation and aggregation has been shown to be heightened in the setting of acute coronary syndromes and to be an independent predictor of adverse events. Blocking platelet aggregation with medical therapy (aspirin, clopidogrel, glycoprotein [GP]IIb/IIIa antagonists) has been demonstrated to be of unequivocal benefit. GPIIb/IIIa is a platelet-specific adhesion receptor that mediates the formation of platelet aggregates. Tirofiban is a small, synthetic, nonpeptide, competitive GPIIb/IIIa antagonist with high specificity and affinity for the GPIIb/IIIa receptor. The Platelet Receptor Inhibition for ischemic Syndrome Management (PRISM) and Platelet Receptor Inhibition for ischemic Syndrome Management in Patients Limited by Unstable signs and Symptoms (PRISM-PLUS) studies found that tirofiban, administered in the upstream setting - based on an infusion of a 30-min bolus - reduced the incidence of major adverse cardiovascular events in patients with non-ST segment elevation acute coronary syndromes, compared with heparin alone. Accordingly, the use of tirofiban in this setting has become a class I indication in the US and European guidelines. A 3-min bolus was also developed to allow the use of tirofiban directly in the catheterization laboratory. However, the do Tirofiban And ReoPro Give Similar Efficacy Trial (TARGET) study has demonstrated clinical inferiority of tirofiban versus abciximab due to suboptimal platelet inhibition soon after administration of 10 microg/kg bolus. To achieve an inhibition of platelet aggregation of more than 90% in the first hour after treatment, a new bolus of tirofiban was identified (10-25 microg/kg). The first case-control and randomized studies based on this new regimen have shown that this dosage was safe and effective in reducing the incidence of adverse events in patients treated with percutaneous coronary intervention. Several Phase II and III studies are ongoing to extend these preliminary findings.