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(Circulation. 2001;104:2772.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Attenuation of Rebound Ischemia After Discontinuation of Heparin Therapy by Glycoprotein IIb/IIIa Inhibition With Eptifibatide in Patients With Acute Coronary Syndromes

Observations From the Platelet IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) Trial

Michael A. Lauer, MD; Penny L. Houghtaling, MS; John G. Peterson, MD; Christopher B. Granger, MD; Deepak L. Bhatt, MD; Shelly K. Sapp, MS; Maarten L. Simoons, MD; Robert A. Harrington, MD; Eric J. Topol, MD; A. Michael Lincoff, MD

From Borgess Research Institute, Kalamazoo, Mich (M.A.L.); the Departments of Biostatistics (P.L.H., S.K.S) and Cardiology (J.G.P., D.L.B., E.J.T., A.M.L.); and Cleveland Clinic Foundation, Cleveland, Ohio; Erasmus University, Rotterdam, the Netherlands (M.L.S.); and the Department of Cardiology, Duke University Medical Center, Durham, NC (C.B.G., R.A.H.).

Correspondence to A. Michael Lincoff, MD, Department of Cardiology, Desk F-25, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195.

Background— A reactivation of ischemia after the discontinuation of intravenous heparin in acute coronary syndromes has been described. The effect of glycoprotein IIb/IIIa blockade on heparin rebound is unknown.

Methods and Results— Patients with acute coronary syndromes who received heparin therapy but not initial revascularization in the Platelet IIb/IIIa in Unstable angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial were analyzed. Rates of death or myocardial (re)infarction while on heparin therapy and in 12-hour periods in the 2 days after heparin discontinuation were compared between eptifibatide and placebo. There was no difference between study groups in event rates during heparin infusion. In the 12 hours after heparin discontinuation, there was a 2.5-fold increase in all events, an 8-fold increase in death, and a 2-fold increase in myocardial infarction. 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 the placebo group. When only considering patients who were on study drug at the time of heparin discontinuation, the reduction in the combined end point was marginally significant, but the difference in the rate of death remained significant (0.68% versus 0.06%, P=0.004). In logistic regression analyses, the multivariate predictors of rebound events were the duration of heparin therapy, age, North American site, and lack of eptifibatide treatment.

Conclusions— An increase in death or myocardial infarction occurs in the 12 hours after heparin discontinuation in patients with acute coronary syndromes. This rebound is attenuated by glycoprotein IIb/IIIa inhibition with eptifibatide.

Key Words: heparin • ischemia • glycoproteins • platelets • mortality

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