(Circulation. 1997;96:1117-1121.)
© 1997 American Heart Association, Inc.
Articles |
Sustained Platelet Glycoprotein IIb/IIIa Blockade With Oral Xemilofiban in 170 Patients After Coronary Stent Deployment
From the Department of Cardiology and Internal Medicine (D.J.K., J.P.R.), University of Cincinnati College of Medicine (Ohio); Division of Cardiology (N.K.), Baylor University College of Medicine; St Luke's Episcopal Hospital (J.J.F.), Texas Heart Institute, Baylor College of Medicine at the University of Texas Health Sciences Center; The Ohio Heart Health Center (T.M.B.); The Carl and Edyth Lindner Center for Clinical Cardiovascular Research at The Health Alliance of Greater Cincinnati (N.A.H., L.H.M.) (Ohio); and G.D. Searle & Co (G.H., S.M., R.J.A.), Skokie, Ill.
Correspondence to Dean J. Kereiakes, MD, FACC, The Carl and Edyth Lindner Center for Clinical Cardiovascular Research, 2123 Auburn Ave, Suite 424, Cincinnati, OH 45219.
Background Inhibition of platelet aggregation with parenteral glycoprotein (GP) IIb/IIIa receptor blockers can reduce the ischemic complications of angioplasty. Sustained efficacy and safety of protracted GP IIb/IIIa blockade with an orally administered agent have not previously been determined. This study is the first randomized, dose-ranging, single-blind, placebo-controlled trial of xemilofiban, an oral platelet GP IIb/IIIa receptor antagonist, administered to patients after intracoronary stent deployment. The pharmacodynamic efficacy of xemilofiban-induced platelet inhibition and clinical safety of this agent was evaluated during chronic therapy.
Methods and Results After elective intracoronary
stent deployment, patients were randomized to receive placebo (250 mg
ticlopidine PO BID) or xemilofiban in doses of 5, 10, 15, or 20 mg PO
BID. All patients received 325 mg aspirin PO QD. Inhibition of ex vivo
platelet aggregation in response to 20 µmol/L ADP and 4
µg/mL collagen was measured over time after the initial dose of study
drug and at 1 and 2 weeks of chronic therapy. Study drug was
discontinued after 2 weeks, and all patients were followed clinically
for 
30 days. Oral xemilofiban resulted in a dose-dependent inhibition
of platelet aggregation in response to both agonists that was
sustained through 2 weeks of chronic therapy. Doses of xemilofiban
required to achieve 50% inhibition of platelet aggregation were
10 mg, and the duration of inhibition was 8 to 10 hours. No
significant hemorrhagic episodes or blood transfusions were observed in
this trial.
Conclusions Oral xemilofiban in doses of 10 mg produced
50% inhibition of platelet aggregation in response to ADP and
collagen for 8 to 10 hours after dosing. Platelet inhibition was
sustained through 2 weeks of chronic therapy. The optimal duration of
oral GP IIb/IIIa blockade to effectively suppress recurrent
ischemic events after coronary intervention remains to
be determined.
Key Words: stents • thrombosis • myocardial infarction • antagonists, receptor
This article has been cited by other articles:
 |
|
 |
|
  D. W. Bougie, P. R. Wilker, E. D. Wuitschick, B. R. Curtis, M. Malik, S. Levine, R. N. Lind, J. Pereira, and R. H. Aster Acute thrombocytopenia after treatment with tirofiban or eptifibatide is associated with antibodies specific for ligand-occupied GPIIb/IIIa Blood, August 28, 2002; 100(6): 2071 - 2076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. P. Chew and D. J. Moliterno A critical appraisal of platelet glycoprotein IIb/IIIa inhibition J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2028 - 2035. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Verstraete Synthetic Inhibitors of Platelet Glycoprotein IIb/IIIa in Clinical Development Circulation, February 15, 2000; 101 (6): e76 - e80. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Vorchheimer, J. J. Badimon, and V. Fuster Platelet Glycoprotein IIb/IIIa Receptor Antagonists in Cardiovascular Disease JAMA, April 21, 1999; 281(15): 1407 - 1414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Zaacks, P. R. Liebson, J. E. Calvin, J. E. Parrillo, and L. W. Klein Unstable angina and non-Q wave myocardial infarction: does the clinical diagnosis have therapeutic implications? J. Am. Coll. Cardiol., January 1, 1999; 33(1): 107 - 118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.F. Storey, R.G. Wilcox, and S. Heptinstall Differential Effects of Glycoprotein IIb/IIIa Antagonists on Platelet Microaggregate and Macroaggregate Formation and Effect of Anticoagulant on Antagonist Potency : Implications for Assay Methodology and Comparison of Different Antagonists Circulation, October 20, 1998; 98(16): 1616 - 1621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Kereiakes, N. S. Kleiman, J. J. Ferguson, A. R. Z. Masud, T. M. Broderick, C. W. Abbottsmith, J. P. Runyon, L. C. Anderson, R. J. Anders, R. J. Dreiling, et al. Pharmacodynamic Efficacy, Clinical Safety, and Outcomes After Prolonged Platelet Glycoprotein IIb/IIIa Receptor Blockade With Oral Xemilofiban : Results of a Multicenter, Placebo-Controlled, Randomized Trial Circulation, September 29, 1998; 98(13): 1268 - 1278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. G. Frederick, O. D. Suleymanov, J. A. Szalony, B. B. Taite, A. K. Salyers, L. W. King, L. P. Feigen, and N. S. Nicholson Protective Effect of Oral Xemilofiban in Arterial Thrombosis in Dogs : Increased Activity in Combination With Aspirin Circulation, August 25, 1998; 98(8): 813 - 820. [Abstract] [Full Text] [PDF]
|
|