Platelet inhibition with tirofiban early during percutaneous coronary intervention: dosing revisited.
Platelet inhibition is central to the efficacy of the intravenous glycoprotein IIb/IIIa receptor inhibitors. Differences in the degree of platelet inhibition achieved with these agents may account for the disparity in clinical efficacy noted in recently completed clinical trials. The purpose of this study was to evaluate ex vivo platelet inhibition with tirofiban in patients admitted with acute coronary syndrome and who were referred for percutaneous coronary interventions. Twenty-five patients were studied. Ten patients received tirofiban 10 microg/kg bolus and 0.15 microg/kg infusion for 16 hr. Platelet inhibition was determined at 5, 15, 30, 45, 60, and 120 min after tirofiban, by light transmission aggregometry (LTA), rapid platelet function assay (RPFA), and platelet works (PW). The average platelet inhibition using RPFA with PPACK, was 87% at 5 min, then decreased to a nadir of 72% at 30 min and recovered back to > 80% at 60 min and onward. Similar trends were noted with RPFA-citrate, PW, and LTA. Ca-chelating anticoagulants (EDTA and citrate) overestimated platelet inhibition at all time points. Dose adjustment was done by increasing the bolus (15 microg/kg) in five patients, increasing the maintenance dose (0.2 microg/kg/min) in five patients, and increasing both the bolus and the maintenance dose in another five patients. Platelet inhibition tested by all the above methods was consistently over 90% when both the bolus and maintenance doses were increased. No increased incidence of major bleeding was noted at this adjusted dose. The current dosing of tirofiban may be inadequate to achieve appropriate platelet inhibition during PCI in patients admitted with acute coronary syndrome and receiving tirofiban immediately before the procedure in the cardiac catheterization laboratory. Dose adjustment may be needed to maximize platelet inhibition early during PCI.
Department of Medicine, Section of Cardiology, Baylor College of Medicine, Houston, Texas, USA. nlakkis@bcm.tmc.edu
Nasser
N
Lakkis
Nada
N
Lakiss
Jeremy
J
Bobek
John
J
Farmer
D006328:Cardiac Catheterization; D003327:Coronary Disease / Q000628:therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D010979:Platelet Function Tests; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D015642:Radiology, Interventional; D000077466:Tirofiban; D014443:Tyrosine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000077466:Tirofiban