Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes
Ff. O'Connor et al., Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes, BLOOD, 98(12), 2001, pp. 3256-3260
This study examined the influence of the PIA polymorphism of glycoprotein I
IIa (GPIIIa) in determining the response to an oral GPIIb/IIIa antagonist,
orbofiban, in patients with unstable coronary syndromes. Genotyping for the
PIA polymorphism was performed in 1014 patients recruited into the OPUS-TI
MI-16 (orbofiban in patients with unstable coronary syndromes-thrombolysis
in myocardial infarction 16) trial, in which patients were randomized to lo
w- or high-dose orbofiban or placebo for 1 year. The primary end point (n =
165) was a composite of death, myocardial infarction (MI), recurrent ische
mia requiring rehospitalization, urgent revascularization, and stroke. Over
all, orbofiban failed to reduce ischemic events when compared with placebo,
but increased the rate of bleeding. In the whole population, PIA2 carriers
had a significant increase in MI (n = 33) during follow up, with a relativ
e risk (RR) of 2.71 (95% CI, 1.37 to 5.38; P = .004). There was a significa
nt interaction between treatment (placebo and orbofiban) and the PIA polymo
rphism for bleeding (n = 187; P = .05). Thus, while orbofiban increased ble
eding in noncarriers (RR = 1.87, 1.29 to 2.71; P < .001) in a dose-dependen
t fashion, it did not increase bleeding events in PIA2 carriers (RR = 0.87,
0.46 to 1.64). There was no Interaction between treatment (placebo and orb
ofiban) and the PIA polymorphism for the primary end point (P = .10). Howev
er, in the patients receiving orbifiban there was a higher risk of a primar
y event (RR = 1.55, 1.03 to 2.34; P = .04) and MI (RR 4.27, 1.82 to 10.03;
P < .001) in PIA2 carriers compared with noncarriers. In contrast, there wa
s no evidence that PIA2 influenced the rate of recurrent events in placebo-
treated patients. In patients presenting with an acute coronary syndrome, t
he PIA polymorphism of GPIIb/IIIa may explain some of the variance in the r
esponse to an oral GPIIb/IIIa antagonist. (Blood. 2001;98:3256-3260) (C) 20
01 by The American Society of Hematology.