Published Online
on July 19, 2004

A more recent version of this article appeared on August 10, 2004

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Submitted on January 12, 2004
Revised on May 4, 2004
Accepted on May 6, 2004

Association Between Platelet Receptor Occupancy After Eptifibatide (Integrilin) Therapy and Patency, Myocardial Perfusion, and ST-Segment Resolution Among Patients With ST-Segment-Elevation Myocardial Infarction. An INTEGRITI (Integrilin and Tenecteplase in Acute Myocardial Infarction) Substudy

C. Michael Gibson MS, MD^*, Lisa K. Jennings PhD, Sabina A. Murphy MPH, David P. Lorenz MD, Robert P. Giugliano MD, SM, Robert A. Harrington MD, Shila Cholera BSMT, Rajini Krishnan BSMT, Robert M. Califf MD, Eugene Braunwald MD, for the INTEGRITI Study Group

From the TIMI Study Group and the Department of Medicine, Brigham & Women’s Hospital, Harvard Medical School (C.M.G., D.P.L., R.P.G., S.A.M., E.B.), Boston, Mass; the University of Tennessee Health Science Center (L.K.J., S.C., R.K.), Memphis, Tenn; and the Duke Clinical Research Institute (R.A.H., R.M.C.), Durham, NC.

Background--Paradoxically, fibrinolytic agents may systemically activate platelets, which in turn secrete plasminogen activator inhibitor (PAI-1), an antagonist of the fibrinolytic process in proportion to total body platelet mass. We hypothesized that improved epicardial patency, myocardial perfusion, and ST-segment resolution would be associated with higher levels of platelet receptor occupancy (RO) by a glycoprotein IIb/IIIa antagonist in ST-elevation MI (STEMI).

Methods and Results--Patients were drawn from the low-dose tenecteplase plus eptifibatide arm of the INTEGRITI study. Angiographic and platelet RO data were analyzed at 2 independent core laboratories. To take into account the absolute platelet count and receptors available for cross-linking, absolute platelet count was multiplied by percent of available receptors to obtain the index of the absolute number of receptors available (IANRA). Percent RO was higher among patients with a patent artery (TIMI flow grade 2/3; 78.2±9.2, n=63 versus 63.9±29.7, n=7; P=0.005), those with TIMI myocardial perfusion grade 2/3 (79.6±9.5, n=40 versus 73.0±16.2, n=30; P=0.036), and those with complete (70%) ST-segment resolution at 60 minutes (81.3±8.3%, n=27 versus 73.1±17.4%, n=24; P=0.034). The absolute number of glycoprotein IIb/IIIa receptors available for cross-linking was reduced (ie, the IANRA was lower) among patients with a patent artery (P=0.0015), patients with TIMI myocardial perfusion grade 2/3 (P=0.026), and patients with 70% ST-segment resolution (P=0.029).

Conclusions--This study links restoration of epicardial flow, normal myocardial perfusion, and complete ST-segment resolution with higher levels of platelet glycoprotein IIb/IIIa receptor occupancy after therapy with eptifibatide administered with tenecteplase.

Key words: platelets • receptors • perfusion • blood flow

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