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

Author:

Batchelor Wayne B.1,Tolleson Thaddeus R.1,Huang Yao1,Larsen Rhonda L.1,Mantell R. Michael1,Dillard Patricia1,Davidian Marie1,Zhang Daowen1,Cantor Warren J.1,Sketch Michael H.1,Ohman E. Magnus1,Zidar James P.1,Gretler Daniel1,DiBattiste Peter M.1,Tcheng James E.1,Califf Robert M.1,Harrington Robert A.1

Affiliation:

1. 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.).

Abstract

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

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