Published Online
on September 3, 2002

A more recent version of this article appeared on September 17, 2002

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Submitted on January 29, 2002
Revised on June 26, 2002
Accepted on June 26, 2002

Randomized COMparison of Platelet Inhibition With Abciximab, TiRofiban and Eptifibatide During Percutaneous Coronary Intervention in Acute Coronary Syndromes. The COMPARE Trial

Wayne B. Batchelor MD, MHS^*, Thaddeus R. Tolleson MD, Yao Huang MS, Rhonda L. Larsen PA-C, MHS, R. Michael Mantell RCVT, Patricia Dillard BA, Marie Davidian PhD, Daowen Zhang PhD, Warren J. Cantor MD, Michael H. Sketch Jr MD, E. Magnus Ohman MD, James P. Zidar MD, Daniel Gretler MD, Peter M. DiBattiste MD, James E. Tcheng MD, Robert M. Califf MD, and Robert A. Harrington MD

From the Tallahassee Heart and Vascular Institute, Tallahassee, Fla (W.B.B); Duke Clinical Research Institute, Durham, NC (T.R.T., R.L.L., J.H., R.M.M., P.D., Y.H., M.H.S., E.M.O., J.P.Z., J.E.T., R.M.C., R.A.H.); St. Michael's Hospital, Toronto, Ontario, Canada (W.J.C.); North Carolina State University, Raleigh (M.D., D.Z.); COR Therapeutics, Inc, South San Francisco, California (D.G.); and Merck & Co, Inc, West Point, Pa (P.M.D.).

^* To whom correspondence should be addressed. E-mail: batch002{at}earthlink.net.

Background—The relative anti-aggregatory effects of currently prescribed platelet glycoprotein IIb/IIIa receptor antagonists during and after percutaneous coronary intervention for acute coronary syndromes have not been established.

Methods and Results—We randomized 70 acute coronary syndrome patients undergoing percutaneous coronary intervention to receive abciximab, eptifibatide, or tirofiban at doses used in the Evaluation of Platelet IIb/IIIa Inhibitor for STENTing (EPISTENT), Platelet glycoprotein IIb/IIIa in Unstable angina Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet Receptor Inhibition in ischemic Syndrome Management in Patients Limited by Unstable Signs and symptoms (PRISM-PLUS)/Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis (RESTORE) trials, respectively. Platelet aggregation (PA) in response to 20 µmol/L of adenosine diphosphate was measured with turbidimetric aggregometry in both D-phenylalanyl-L-prolyl-L-arginine chloromethylketone and citrate-anticoagulated blood early (15 and 30 minutes) and late (4, 12, and 18 to 24 hours) after drug initiation. At 15 and 30 minutes, PA was significantly less inhibited by the tirofiban-RESTORE regimen compared with abciximab (P=0.028) and eptifibatide regimens (P=0.0001). The abciximab regimen, however, showed increasingly varied anti-aggregatory effects during continued infusion for 4 hours. Citrate exaggerated ex vivo platelet inhibition after eptifibatide and tirofiban, but had the opposite effect on abciximab. Of all regimens evaluated, the eptifibatide regimen inhibited PA most consistently throughout both the early and late periods.

Conclusions—Currently recommended drug regimens to inhibit the platelet glycoprotein IIb/IIIa receptor have distinct pharmacodynamic profiles that might affect their relative efficacy in acute coronary syndromes and percutaneous coronary intervention.

Key words: platelets • coronary disease • glycoproteins • angioplasty

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