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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3224-3229.)
© 1997 American Heart Association, Inc.

Articles

Continued Thromboxane A₂ Formation Despite Administration of a Platelet Glycoprotein IIb/IIIa Antagonist in Patients Undergoing Coronary Angioplasty

Anthony Byrne; Niamh Moran; Maureen Maher; Noleen Walsh; Peter Crean; ; Desmond J. Fitzgerald

From Centre for Cardiovascular Science, Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin, and Department of Cardiology (N.W., P.C.), St. James Hospital, Dublin.

Correspondence to Dr. Anthony Byrne, Centre for Cardiovascular Science, Royal College of Surgeons in Ireland, St Stephens Green, Dublin 2, Ireland. E-mail dfitzgerald{at}rcsi.ie

Abstract Experimental data suggest that formation of thromboxane A₂ may be suppressed during administration of a glycoprotein IIb/IIIa antagonist. We determined the dose of one such compound, fradafiban, required to provide >80% occupancy of the platelet glycoprotein IIb/IIIa and examined its effects on thromboxane A₂ formation in patients undergoing PTCA. The dose response to fradafiban and additional effects of aspirin were explored initially in patients with stable coronary artery disease. Fradafiban induced a dose-dependent inhibition of platelet aggregation that correlated with fibrinogen receptor occupancy and plasma drug concentration. Addition of aspirin 300 mg had no effect on these parameters. At the highest dose, mean fibrinogen receptor occupancy was 89.7±1.2% (n=3) at 4 hours and platelet aggregation had decreased by 93.4±2.7%. Eighteen patients undergoing coronary angioplasty were randomized to receive either aspirin 330 mg or that dose of fradafiban producing >80% fibrinogen receptor occupancy. Platelet aggregation was suppressed throughout the infusion of fradafiban to a greater extent than with aspirin. However, there was a marked increase in urinary excretion of 11-dehydrothromboxane B₂ in patients treated with fradafiban: from 1973±889 to a peak of 9760±3509 pg/mg creatinine (P=.0046). Despite this evidence of continued platelet activation in vivo, there were no cases of coronary thrombosis. In conclusion, fradafiban suppresses platelet aggregation and may be a useful alternative to aspirin in the prevention of thrombotic events in patients undergoing PTCA. However, there is continued formation of thromboxane A₂, which may continue to exert its effects as a potent vasoconstrictor and vascular smooth muscle mitogen.

Key Words: platelet activation • thromboxane • glycoprotein IIb • glycoprotein IIIa • coronary angioplasty

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