Role of oral blockade of platelet glycoprotein IIb/IIIa on neutrophil activation in patients with acute coronary syndromes.
Orbofiban is a unique antiplatelet agent that inhibits the binding of fibrinogen to gycoprotein (GP) IIb/IIIa integrin receptors and thus prevents platelet aggregation induced by various agents. However, recent studies indicate that treatment with orbofiban does not reduce the incidence of recurrent ischemic events. The mechanisms underlying the lack of benefit of orbofiban in patients with acute coronary syndromes are not completely clear. The purpose of this study was to characterize the effects of orbofiban on cellular activation (neutrophil superoxide generation) and surface expression of adhesion molecules of circulating neutrophils (CD18, CD11b, and L-selectin) and platelets (P-selectin and GP IIb/IIIa) in patients with acute coronary syndromes. After 5-7 days, orbifiban (50 mg BID) did not reduce PMN adhesion molecule expression and ex vivo-stimulated PMN superoxide generation--as was observed in the placebo group, without orbofiban. In contrast, orbofiban induced marked reductions in GP IIb/IIIa and P-selectin expressions after 5-7 days of treatment. The sustained neutrophil activation observed with orbofiban may have a role on the recurrent thrombotic events observed with orbofiban treatment in the OPUS-TIMI 16 trial.
Serrano
Carlos V
CV
Heart Institute (InCor), University of São Paulo, Medical School, São Paulo, SP, Brazil. dclserrano@incor.usp.br
Nicolau
José C
JC
Venturinelli
Margareth
M
Baracioli
Luciano M
LM
Anders
Robert J
RJ
Cannon
Christopher P
CP
Ramires
José A F
JA
D000208:Acute Disease; D000409:Alanine / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy*; D018375:Neutrophil Activation / Q000187:drug effects*; D015539:Platelet Activation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D011759:Pyrrolidines / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D013481:Superoxides / Q000378:metabolism; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011759:Pyrrolidines; D013481:Superoxides; C120234:orbofiban; D000409:Alanine