TY - JOUR
T1 - Combined accelerated tissue-plasminogen activator and platelet glycoprotein IIb/IIIa integrin receptor blockade with integrilin in acute myocardial infarction
T2 - Results of a randomized, placebo-controlled, dose- ranging trial
AU - Magnus Ohman, E.
AU - Kleiman, Neal S.
AU - Gacioch, Gerald
AU - Worley, Seth J.
AU - Navetta, Frank I.
AU - David Talley, J.
AU - Vernon Anderson, H.
AU - Ellis, Stephen G.
AU - Cohen, Mark D.
AU - Spriggs, Douglas
AU - Miller, Michael
AU - Kereiakes, Dean
AU - Yakubov, Steven
AU - Kitt, Michael M.
AU - Sigmon, Kristina N.
AU - Califf, Robert M.
AU - Krucoff, Mitchell W.
AU - Topol, Eric J.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - myocardial infarction
KW - platelet aggregation inhibitors
KW - reperfusion
KW - thrombolysis
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U2 - 10.1161/01.cir.95.4.846
DO - 10.1161/01.cir.95.4.846
M3 - Article
C2 - 9054741
AN - SCOPUS:16944362255
VL - 95
SP - 846
EP - 854
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 4
ER -