TY - JOUR
T1 - Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention
AU - Harrington, Robert A.
AU - Kleiman, Neal
AU - Kottke-Marchant, Kandice
AU - Lincoff, A. Michael
AU - Tcheng, James E.
AU - Sigmon, Kristina N.
AU - Joseph, Diane
AU - Rios, Gaddiel
AU - Trainor, Kathleen
AU - Rose, Dale
AU - Greenberg, Charles S.
AU - Kitt, Michael M.
AU - Topol, Eric J.
AU - Califf, Robert M.
N1 - Funding Information:
From the Divisions of Cardiol y and Hematolo yOncology. University Medical Center, Dur“ il am, North Caro Pi na; the Division Cardiology, Baylor College of Medicine, Houston, Texas; the Depart ment of Cardiolo y, The Cleveland Clinic Foundation, Cleveland, Ohio; and COR T 9, erapeutics, Inc., South San Francisco, California. This study was supported in part by a grant from COR Therapeutics, Inc.. South San Francisco, California. Manuscript received June 14, 1995; revised manuscript received and accepted August 3 1, 1995.
Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 1995/12/15
Y1 - 1995/12/15
N2 - We studied the pharmacokinetic and pharmacodynamic properties or integrelin, a novel platelet glycoprotein IIb/IIIa receptor inhibitor, in patients undergoing elective percutaneous coronary intervention. Patients were randomized to placebo (n = 19) or to 1 of 4 integrelin dosing regimens (total n = 54) that were studied sequentially. All patients received aspirin and heparin. Patients were followed until discharge for the occurrence of adverse clinical events: death, myocardial infarction, coronary artery bypass surgery, repeat intervention, or recurrent ischemia. Bleeding was the primary safety end point. Frequent blood sampling was performed for adenosine diphosphate-induced platelet aggregations. Simplate bleeding times were performed. Adverse clinical events occurred less often in the integrelin-treated patients, although the overall numbers were too small to make a definitive statement as to clinical efficacy. There was no significant increase in serious bleeding among integrelin-treated patients. The 2 highest inregrelin boluses (180 and 135 gmg/kg) immediately (15 minutes after the bolus) provided >80% inhibition of adenosine diphosphate-induced platelet aggregation in >75% of treated patients. A constant inregrelin infusion of 0.75 μg/kg/min maintained this marked antiplatelet effect, whereas an infusion of 0.50 μg/kg/min allowed gradual recovery of platelet function. Elective coronary intervention was performed safely and with no significant increase in serious bleeding events using inregrelin with aspirin and heparin as an antithrombotic regimen. Integrelin provided rapid, intense, and persistent ex vivo platelet inhibition during coronary intervention. This new antiplatelet agent may be beneficial in reducing platelet-mediated ischemic complications of percutaneous coronary intervention.
AB - We studied the pharmacokinetic and pharmacodynamic properties or integrelin, a novel platelet glycoprotein IIb/IIIa receptor inhibitor, in patients undergoing elective percutaneous coronary intervention. Patients were randomized to placebo (n = 19) or to 1 of 4 integrelin dosing regimens (total n = 54) that were studied sequentially. All patients received aspirin and heparin. Patients were followed until discharge for the occurrence of adverse clinical events: death, myocardial infarction, coronary artery bypass surgery, repeat intervention, or recurrent ischemia. Bleeding was the primary safety end point. Frequent blood sampling was performed for adenosine diphosphate-induced platelet aggregations. Simplate bleeding times were performed. Adverse clinical events occurred less often in the integrelin-treated patients, although the overall numbers were too small to make a definitive statement as to clinical efficacy. There was no significant increase in serious bleeding among integrelin-treated patients. The 2 highest inregrelin boluses (180 and 135 gmg/kg) immediately (15 minutes after the bolus) provided >80% inhibition of adenosine diphosphate-induced platelet aggregation in >75% of treated patients. A constant inregrelin infusion of 0.75 μg/kg/min maintained this marked antiplatelet effect, whereas an infusion of 0.50 μg/kg/min allowed gradual recovery of platelet function. Elective coronary intervention was performed safely and with no significant increase in serious bleeding events using inregrelin with aspirin and heparin as an antithrombotic regimen. Integrelin provided rapid, intense, and persistent ex vivo platelet inhibition during coronary intervention. This new antiplatelet agent may be beneficial in reducing platelet-mediated ischemic complications of percutaneous coronary intervention.
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U2 - 10.1016/S0002-9149(99)80345-2
DO - 10.1016/S0002-9149(99)80345-2
M3 - Article
C2 - 7503000
AN - SCOPUS:0028811436
SN - 0002-9149
VL - 76
SP - 1222
EP - 1227
JO - The American Journal of Cardiology
JF - The American Journal of Cardiology
IS - 17
ER -