Circulation, Vol 89, 596-603, Copyright © 1994 by American Heart Association
ML Simoons, MJ de Boer, MJ van den Brand, AJ van Miltenburg, JC Hoorntje, GR Heyndrickx, LR van der Wieken, D de Bono, W Rutsch and TF Schaible
BACKGROUND: Patients with unstable angina despite intensive medical
therapy, ie, refractory angina, are at high risk for developing thrombotic
complications: myocardial infarction or coronary occlusion during
percutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E3)
Fab is an antibody fragment that blocks the platelet glycoprotein (GP)
IIb/IIIa receptor and potently inhibits platelet aggregation. METHODS AND
RESULTS: To evaluate whether potent platelet inhibition could reduce these
complications, 60 patients with dynamic ST-T changes and recurrent pain
despite intensive medical therapy were randomized to c7E3 Fab or placebo.
After initial angiography had demonstrated a culprit lesion suitable for
PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus injection
followed by 10 micrograms/min for 18 to 24 hours until 1 hour after
completion of second angiography and PTCA. During study drug infusion,
ischemia occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During
hospital stay, 12 major events occurred in 7 placebo patients (23%),
including 1 death, 4 infarcts, and 7 urgent interventions. In the c7E3 Fab
group, only 1 event (an infarct) occurred (3%, P = .03). Angiography showed
improved TIMI flow in 4 placebo and 6 c7E3 Fab patients and worsening of
flow in 3 placebo patients but in none of the c7E3 Fab patients.
Quantitative analysis showed significant improvement of the lesion in the
patients treated with c7E3 Fab, which was not observed in the placebo
group, although the difference between the two treatment groups was not
significant. Measurement of platelet function and bleeding time
demonstrated > 90% blockade of GPIIb/IIIa receptors, > 90% reduction
of ex vivo platelet aggregation to ADP, and a significantly prolonged
bleeding time during c7E3 Fab infusion, without excess bleeding.
CONCLUSIONS: Combined therapy with c7E3 Fab, heparin, and aspirin appears
safe. These pilot study results support the concept that effective blockade
of the platelet GPIIb/IIIa receptors can reduce myocardial infarction and
facilitate PTCA in patients with refractory unstable angina.
ARTICLES
Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. European Cooperative Study Group
Thoraxcenter, Rotterdam, The Netherlands.
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