Single high-dose bolus tirofiban with high-loading-dose clopidogrel in primary coronary angioplasty

Abstract

Glycoprotein IIb/IIIa inhibitor therapy during primary percutaneous coronary intervention (PCI) decreases the incidence of major adverse cardiac events. These effects directly result from the level of platelet inhibition. It was shown that standard dosing of tirofiban is insufficient for optimal platelet inhibition. We sought to determine the efficacy and safety of single high-dose bolus (HDB) tirofiban with high-dose clopidogrel loading in primary PCI in acute ST elevation myocardial infarction. A total of 100 patients (mean age 55.2 +/- 9.9 years, male/female = 86/14) undergoing primary PCI, pretreated with clopidogrel (450 mg) and aspirin (325 mg), were consecutively randomized into two groups. Group I (n = 50) received a standard dose bolus of tirofiban (10 microg/kg/3 min) with 24-h infusion at a rate of 0.15 microg/kg/min. Group II received single HDB tirofiban (25 microg/kg/3 min). The assessed angiographic, clinical, and echocardiographic endpoints were: initial and final Thrombolysis in Myocardial Infarction (TIMI) grade flow (TGF), corrected TIMI frame count (CTFC), ST-segment resolution (STR) at 90 min, in-hospital bleeding complications, echocardiographic left ventricular ejection fraction (LVEF), death, reinfarction, and repeat target vessel revascularization at 1 month. Platelet function inhibition was measured using PFA-100 (Behring-Dade, Liederbach, Germany) with a test cartridge unit containing a membrane coated with 2 microg of equine Type I collagen and 50 microg adenosine diphosphate before, and 10 min, 2, 4, 6, 12, and 24 h after the bolus of the tirofiban in the first 10 cases of each group. There were no significant differences in baseline characteristics between groups. Initial TGF III was more frequent (24% vs 8%, P = 0.029) and the value of CTFC was lower (75 +/- 34 vs 89 +/- 25, P = 0.03) in group II. Postprocedural TGF, CTFC, STR, bleeding complications, and LVEF at 1 month were not different between the two groups. There was a higher rate of reinfarction in group II (8%) compared with group I (2%), but this difference was not statistically significant (P > 0.05). The results of platelet function analyses showed that group II patients had significantly prolonged platelet function assay closure times (299 +/- 6 s) compared with group patients (236 +/- 97 s) at 10 min after the bolus dose (P = 0.04). However, after the first dose between 2 and 24 h, PFA closure times were significantly prolonged in patients with tirofiban infusion. High-dose bolus of tirofiban seems to be safe and more effective than conventional dose at the periprocedural time, whereas continuous infusion of tirofiban may be necessary in the first 24 h before stable and safe antiplatelet status is reached with clopidogrel. However, safety and efficacy of HDB tirofiban and high-loading-dose clopidogrel together with tirofiban infusion requires further studies with a larger population.