Profound inhibition of platelet aggregation with monoclonal antibody 7E3 Fab thrombolytic therapy. Results of the thrombolysis and angioplasty in mycardial infaraction (TAMI) 8 pilot study

Neal S. Kleiman, E. Magnus Ohman, Robert M. Califf, Barry S. George, Dean Kereiakes, Frank V. Aguirre, Harlan Weisman, Thomas Schaible, Eric J. Topol

Research output: Contribution to journalArticle

312 Scopus citations

Abstract

Objectives. This study was undertaken to establish evidence for physiologic activity and to study the safety of murine-derived monoclonal antibody 7E3 Fab (m7E3 Fab) in receiving recombinant tissue-type plasminogen activator (rt-PA). Background. Platelet aggregation is believed to be a significant factor in the failure of pharmacologic reperfusion. By binding to the glycoprotein IIb/IHa receptor, m7E3 Fab inhibits platelet aggregation and has been shown experimentally to decrease the time required for lysis and to prevent reocclusion. However, the safety of profound platelet inhibition after thrombolysis for acute myocardial infarction has not been tested in humans. Methods. Sixty patients receiving rt-PA, aspirin and heparin for acute myocardial infarction received m7E3 Fab bolus injections in ascending doses at 3, 6 and 15 h after initiation of the thrombolytic infusion. Ten patients treated with rt-PA but not m7E3 Fab were studied as control subjects. Results. Receptor site blockade and inhibition of platelet aggregation to 20 μmol/liter adenosine were maximal at a dose of 0.25 mg/kg body of m7E3 Fab. Fifteen (25%) m7E3 Fab-treated patients and five (50%) control patients had major bleeding; eight of these events in seven m7E3 Fab-treated patients and one in a control patient occurred at the time of aortocoronary bypass surgery. Recurrent ischemia occured in eight (13%) m7E3 Fab-treated patients and two (20%) control subjects. Coronary angiography was performed in 43 patients; the infarct-related coronary artery was patent in 5 of 9 (56%) control patients and 34 (92%) of 37 patients receiving m7E3 Fab. Conclusions. Profound inhibition of platelet aggregation after thrombolysis was associated with bleeding rates comparable to those in control patients and a low rate of recurrent ischemia. The combination of m7E3 Fab and rt-PA, heparin and aspirin appears to be a promising and safe combination that should be evaluated in further studies of patients with acute myocardial infarction.

Original languageEnglish (US)
Pages (from-to)381-389
Number of pages9
JournalJournal of the American College of Cardiology
Volume22
Issue number2
DOIs
StatePublished - Aug 1993

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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