• Robert P Giugliano, Matthew T Roe, Robert A Harrington, C Michael Gibson, Uwe Zeymer, Frans Van de Werf, Kenneth W Baran, Hans Peter Hobbach, Lynn H Woodlief, Karen L Hannan, Sally Greenberg, Joanne Miller, Michael M Kitt, John Strony, Carolyn H McCabe, Eugene Braunwald, Robert M Califf, and INTEGRITI Investigators.
• TIMI Study Group, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. rgiugliano@partners.org
• J. Am. Coll. Cardiol. 2003 Apr 16; 41 (8): 1251-60.

ObjectivesThe goal of this study was to evaluate combinations of eptifibatide with reduced-dose tenecteplase (TNK) in ST-elevation myocardial infarction (STEMI).BackgroundGlycoprotein IIb/IIIa inhibitors enhance thrombolysis. The role of combination therapy in clinical practice remains to be established.MethodsPatients (n = 438) with STEMI <6 h were enrolled. In dose-finding, 189 patients were randomized to different combinations of double-bolus eptifibatide and reduced-dose TNK. In dose-confirmation, 249 patients were randomized 1:1 to eptifibatide 180 microg/kg bolus, 2 microg/kg/min infusion, and 180 microg/kg bolus 10 min later (180/2/180) plus half-dose TNK (0.27 mg/kg) or standard-dose (0.53 mg/kg) TNK monotherapy. All patients received aspirin and unfractionated heparin (60 U/kg bolus; infusion 7 U/kg/h [combination], 12 U/kg/h [monotherapy]). The primary end point was Thrombolysis In Myocardial Infarction (TIMI) grade 3 epicardial flow at 60 min.ResultsIn dose-finding, TIMI grade 3 flow rates were similar across groups (64% to 68%). Arterial patency was highest for eptifibatide 180/2/180 plus half-dose TNK (96%, p = 0.02 vs. eptifibatide 180/2/90 plus half-dose TNK). In dose-confirmation, this combination, compared with TNK monotherapy, tended to achieve more TIMI 3 flow (59% vs. 49%, p = 0.15), arterial patency (85% vs. 77%, p = 0.17), and ST-segment resolution (median 71% vs. 61%, p = 0.08) but was associated with more major hemorrhage (7.6% vs. 2.5%, p = 0.14) and transfusions (13.4% vs. 4.2%, p = 0.02). Intracranial hemorrhage occurred in 1.0%, 0.6%, and 1.7% of patients treated with any combination, eptifibatide 180/2/180 and half-dose TNK, and TNK monotherapy, respectively.ConclusionsDouble-bolus eptifibatide (180/2/180) plus half-dose TNK tended to improve angiographic flow and ST-segment resolution compared with TNK monotherapy but was associated with more transfusions and non-cerebral bleeding. Further study is needed before this combination can be recommended for general use.

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