RANDOMIZED TRIAL OF A GPIIB IIIA PLATELET RECEPTOR BLOCKER IN REFRACTORY UNSTABLE ANGINA/

Background Patients with unstable angina despite intensive medical the rapy, ie, refractory angina, are at high risk for developing thromboti c complications: myocardial infarction or coronary occlusion during pe rcutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E 3) Fab is an antibody fragment that blocks the platelet glycoprotein ( GP) IIb/IIIa receptor and potently inhibits platelet aggregation. Meth ods and Results To evaluate whether potent platelet inhibition could r educe these complications, 60 patients with dynamic ST-T changes and r ecurrent pain despite intensive medical therapy were randomized to c7E 3 Fab or placebo. After initial angiography had demonstrated a culprit lesion suitable for PTCA, placebo or c7E3 Fab was administered as 0.2 5 mg/kg bolus injection followed by 10 mu g/min for 18 to 24 hours unt il 1 hour after completion of second angiography and PTCA. During stud y drug infusion, ischemia occurred in 9 c7E3 Fab and 16 placebo patien ts (P=.06). During hospital stay, 12 major events occurred in 7 placeb o patients (23%), including 1 death, 4 infarcts, and 7 urgent interven tions. 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 o f the c7E3 Fab patients. Quantitative analysis showed significant impr ovement of the lesion in the patients treated with c7E3 Fab, which was not observed in the placebo group, although the difference between th e two treatment groups was not significant. Measurement of platelet fu nction and bleeding time demonstrated >90% blockade of GPIIb/IIIa rece ptors, >90% reduction of ex vivo platelet aggregation to ADP, and a si gnificantly 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 concep t that effective blockade of the platelet GPIIb/IIIa receptors can red uce myocardial infarction and facilitate PTCA in patients with refract ory unstable angina.