Attenuation of rebound ischemia after discontinuation of heparin therapy by glycoprotein IIb/IIIa inhibition with eptifibatide in patients with acutecoronary syndromes - Observations from the platelet IIb/IIIa in unstable angina: Receptor suppression using integrilin therapy (PURSUIT) trial

Background-A reactivation of ischemia after the discontinuation of intraven ous heparin in acute coronary syndromes has been described. The effect of g lycoprotein IIb/IIIa blockade on heparin rebound is unknown. Methods and Results-Patients with acute coronary syndromes who received hep arin therapy but not initial revascularization in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) tr ial were analyzed. Rates of death or myocardial (re)infarction while on hep arin therapy and in 12-hour periods in the 2 days after heparin discontinua tion were compared between eptifibatide and placebo. There was no differenc e between study groups in event rates during heparin infusion. In the 12 ho urs after heparin discontinuation, there was a 2.5-fold increase in all eve nts, an 8-fold increase in death, and a 2-fold increase in myocardial infar ction. However, in the 12 hours after heparin discontinuation, there was a significantly lower rate of events (1.68% versus 2.53%, P = 0.03) and death (0.77% versus 0.21%, P = 0.002) in the eptifibatide group compared with th e placebo group. When only considering patients who were on study drug at t he time of heparin discontinuation, the reduction in the combined end point was marginally significant, but the difference in the rate of death remain ed significant (0.68% versus 0.06%, P = 0.004). In logistic regression anal yses, the multivariate predictors of rebound events were the duration of he parin therapy, age, North American site, and lack of eptifibatide treatment . Conclusions-An increase in death or myocardial infarction occurs in the 12 hours after hepar-in discontinuation in patients with acute coronary syndro mes. This rebound is attenuated by glycoprotein IIb/IIIa inhibition with ep tifibatide.