Immediate and reversible platelet inhibition after intravenous administration of a peptide glycoprotein IIb/IIIa inhibitor during percutaneous coronary intervention

Robert A. Harrington, Neal Kleiman, Kandice Kottke-Marchant, A. Michael Lincoff, James E. Tcheng, Kristina N. Sigmon, Diane Joseph, Gaddiel Rios, Kathleen Trainor, Dale Rose, Charles S. Greenberg, Michael M. Kitt, Eric J. Topol, Robert M. Califf

Research output: Contribution to journalArticlepeer-review

199 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1222-1227
Number of pages6
JournalThe American Journal of Cardiology
Volume76
Issue number17
DOIs
StatePublished - Dec 15 1995

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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