CONTINUED THROMBOXANE A(2) FORMATION DESPITE ADMINISTRATION OF A PLATELET GLYCOPROTEIN IIB IIIA ANTAGONIST IN PATIENTS UNDERGOING CORONARY ANGIOPLASTY/

Experimental data suggest that formation of thromboxane A(2) may be su ppressed during administration of a glycoprotein IIb/IIIa antagonist. We determined the dose of one such compound, fradafiban, required to p rovide >80% occupancy of the platelet glycoprotein IIb/IIIa and examin ed its effects on thromboxane A(2) formation in patients undergoing PT CA. The dose response to fradafiban and additional effects of aspirin were explored initially in patients with stable coronary artery diseas e. Fradafiban induced a dose-dependent inhibition of platelet aggregat ion that correlated with fibrinogen receptor occupancy and plasma drug concentration. Addition of aspirin 300 mg had no effect on these para meters. 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 we re randomized to receive either aspirin 330 mg or that dose of fradafi ban producing >80% fibrinogen receptor occupancy. Platelet aggregation was suppressed throughout the infusion of fradafiban to a greater ext ent than with aspirin. However, there was a marked increase in urinary excretion of 11-dehydrothromboxane B-2 in patients treated with frada fiban: 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, frada fiban suppresses platelet aggregation and may be a useful alternative to aspirin in the prevention of thrombotic events in patients undergoi ng PTCA. However, there is continued formation of thromboxane A(2), wh ich may continue to exert its effects as a potent vasoconstrictor and vascular smooth muscle nitogen.