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(Circulation. 1997;95:846-854.)
© 1997 American Heart Association, Inc.
Articles |
Combined Accelerated Tissue-Plasminogen Activator and Platelet Glycoprotein IIb/IIIa Integrin Receptor Blockade With Integrilin in Acute Myocardial Infarction
Results of a Randomized, Placebo-Controlled, Dose-Ranging Trial
Duke University Medical Center, Durham, NC (E.M.O., K.N.S., R.M.C., M.W.K.); Methodist Hospital (N.S.K.) and the University of Texas Medical Center (H.V.A.), Houston, Tex; Rochester (NY) General Hospital (G.G.); Lancaster (Penn) General Hospital (S.J.W.); Mother Frances Hospital, Tyler, Tex (F.I.N.); University of Louisville (Ky) (J.D.T.); The Cleveland (Ohio) Clinic Foundation (S.G.E., D.D., E.J.T.); St. Francis Hospital, Beech Grove, Ind (M.D.C.); Morton Plant Hospital, Clearwater, Fla (D.S.); University of South Carolina Medical Center, Charleston (M.M.); Christ Hospital, Cincinnati, Ohio (D.K.); MidWest Cardiovascular Research, Columbus, Ohio (S.Y.); and COR Therapeutics, Inc, South San Francisco, Calif (M.M.K.).
Correspondence to E. Magnus Ohman, MD, PO Box 3151, Duke University Medical Center, Durham, NC 27710.
Background Platelet activation and aggregation may be key components of thrombolytic failure to restore and maintain perfusion in acute myocardial infarction. We performed a placebo-controlled, dose-ranging trial of Integrilin, a potent inhibitor of platelet aggregation, with heparin, aspirin, and accelerated alteplase.
Methods and Results We assigned 132 patients in a 2:1 ratio to receive a bolus and continuous infusion of one of six Integrilin doses or placebo. Another 48 patients were randomized in a 3:1, double-blind fashion to receive the highest Integrilin dose from the first phase or placebo. All patients received accelerated alteplase, aspirin, and intravenous heparin infusion; all but two groups also received an intravenous heparin bolus. The highest Integrilin dose group from the nonrandomized phase and the randomized patients were pooled for analysis and compared with placebo-treated patients. The primary end point was Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow at 90-minute angiography. Secondary end points were time to ST-segment recovery, an in-hospital composite (death, reinfarction, stroke, revascularization procedures, new heart failure, or pulmonary edema), and bleeding variables. The highest Integrilin dose groups had more complete reperfusion (TIMI grade 3 flow, 66% versus 39% for placebo-treated patients; P=.006) and a shorter median time to ST-segment recovery (65 versus 116 minutes for placebo; P=.05). The groups had similar rates of the composite end point (43% versus 42% for placebo-treated patients) and severe bleeding (4% versus 5%, respectively).
Conclusions The incidence and speed of reperfusion can be enhanced when a potent inhibitor of the glycoprotein IIb/IIIa integrin receptor, such as Integrilin, is combined with accelerated alteplase, aspirin, and intravenous heparin.
Key Words: myocardial infarction • platelet aggregation inhibitors • reperfusion • thrombolysis
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