Correspondence to David J. Moliterno, MD, Department of Cardiology, F-25, The Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. E-mail molited{at}cesmtp.ccf.org
Background—Unstable angina and
non–Q-wave myocardial infarction involve coronary
arterial plaque rupture, platelet activation, and
thrombus formation. This study tested the benefit of different doses of
lamifiban (a platelet IIb/IIIa antagonist) alone and in
combination with heparin in patients with these conditions to select
the most promising lamifiban regimen for subsequent
evaluation.
Methods and Results—At 273 hospitals in 20 countries, 2282
patients were randomly assigned to lamifiban (2x2 factorial design:
low-dose [1 µg/min] with and without heparin versus high-dose [5
µg/min] with and without heparin) or to standard therapy (placebo
and heparin). All patients received aspirin. The composite primary end
point of death or nonfatal myocardial infarction at 30 days occurred in
11.7% of those receiving standard therapy, 10.6% receiving low-dose
lamifiban, and 12.0% receiving high-dose lamifiban
(P=0.668). By 6 months, this composite was lowest for
those assigned to low-dose lamifiban (P=0.027) and
intermediate for those assigned to high-dose lamifiban
(P=0.450) compared with control (13.7%, 16.4%, and
17.9%, respectively). Compared with control, the combination of
high-dose lamifiban and heparin resulted in more intermediate or major
bleeding (12.1% versus 5.5%; P=0.002) and a similar
rate of ischemic events. Conversely, low-dose lamifiban and
heparin yielded similar bleeding rates as in the control group but
fewer ischemic events at 6 months (12.6% versus 17.9%;
P=0.025).
Conclusions—In unstable angina and non–Q-wave infarction,
platelet IIb/IIIa antagonism with lamifiban reduces adverse
ischemic events at 6 months beyond that of aspirin and heparin
therapy. The role of conjunctive heparin remains uncertain but appears
more favorable with low-dose IIb/IIIa antagonism. Larger-scale study is
needed to more reliably estimate these effects.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
International, Randomized, Controlled Trial of Lamifiban (a Platelet Glycoprotein IIb/IIIa Inhibitor), Heparin, or Both in Unstable Angina
Key Words: angina • myocardial infarction • platelet aggregation inhibitors • heparin
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S. A. Coulter, C. P. Cannon, K. A. Ault, E. M. Antman, F. Van de Werf, A. A. J. Adgey, C. M. Gibson, R. P. Giugliano, M. A. Mascelli, J. Scherer, et al. High Levels of Platelet Inhibition With Abciximab Despite Heightened Platelet Activation and Aggregation During Thrombolysis for Acute Myocardial Infarction : Results From TIMI (Thrombolysis In Myocardial Infarction) 14 Circulation, June 13, 2000; 101(23): 2690 - 2695. [Abstract] [Full Text] [PDF]
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M. Verstraete Synthetic Inhibitors of Platelet Glycoprotein IIb/IIIa in Clinical Development Circulation, February 15, 2000; 101 (6): e76 - e80. [Abstract] [Full Text] [PDF]
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E. J. Topol and J. S. Yadav Recognition of the Importance of Embolization in Atherosclerotic Vascular Disease Circulation, February 8, 2000; 101(5): 570 - 580. [Full Text] [PDF]
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A. Brodison, R. Katira, R. S More, and A. Chauhan Current practice: Antiplatelet use in interventional cardiology Postgrad. Med. J., February 1, 2000; 76(892): 70 - 79. [Abstract] [Full Text]
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J. A. Ambrose and G. Dangas Unstable Angina: Current Concepts of Pathogenesis and Treatment Arch Intern Med, January 10, 2000; 160(1): 25 - 37. [Abstract] [Full Text] [PDF]
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A. T. Nurden, C. Poujol, C. Durrieu-Jais, and P. Nurden Platelet Glycoprotein IIb/IIIa Inhibitors : Basic and Clinical Aspects Arterioscler Thromb Vasc Biol, December 1, 1999; 19(12): 2835 - 2840. [Full Text] [PDF]
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P. J. Zed, J. E. Tisdale, and S. Borzak Low-Molecular-Weight Heparins in the Management of Acute Coronary Syndromes Arch Intern Med, September 13, 1999; 159(16): 1849 - 1857. [Abstract] [Full Text] [PDF]
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P. Aukrust, F. Muller, T. Ueland, T. Berget, E. Aaser, A. Brunsvig, N. O. Solum, K. Forfang, S. S. Froland, and L. Gullestad Enhanced Levels of Soluble and Membrane-Bound CD40 Ligand in Patients With Unstable Angina : Possible Reflection of T Lymphocyte and Platelet Involvement in the Pathogenesis of Acute Coronary Syndromes Circulation, August 10, 1999; 100(6): 614 - 620. [Abstract] [Full Text] [PDF]
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L. F. M. van den Merkhof, F. Zijlstra, H. Olsson, L. Grip, G. Veen, F. W. H. M. Bar, M. J. B. M. van den Brand, M. L. Simoons, and F. W. A. Verheugt Abciximab in the treatment of acute myocardial infarction eligible for primary percutaneous transluminal coronary angioplasty: Results of the glycoprotein receptor antagonist patency evaluation (GRAPE) pilot study J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1528 - 1532. [Abstract] [Full Text] [PDF]
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D. A. Vorchheimer, J. J. Badimon, and V. Fuster Platelet Glycoprotein IIb/IIIa Receptor Antagonists in Cardiovascular Disease JAMA, April 21, 1999; 281(15): 1407 - 1414. [Abstract] [Full Text] [PDF]
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D. F. Kong, R. M. Califf, D. P. Miller, D. J. Moliterno, H. D. White, R. A. Harrington, J. E. Tcheng, A. M. Lincoff, V. Hasselblad, and E. J. Topol Clinical Outcomes of Therapeutic Agents That Block the Platelet Glycoprotein IIb/IIIa Integrin in Ischemic Heart Disease Circulation, December 22, 1998; 98(25): 2829 - 2835. [Abstract] [Full Text] [PDF]
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