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(Circulation. 2004;110:679-684.)
© 2004 American Heart Association, Inc.

Original Articles

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.

Correspondence to C. Michael Gibson, MS, MD, 350 Longwood Ave, First Floor, Boston, MA 02115.

Received January 12, 2004; de novo received March 4, 2004; revision received May 4, 2004; accepted May 6, 2004.

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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