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Randomized trial of a GPIIb/IIIa platelet receptor blocker in refractory unstable angina. European Cooperative Study
M L Simoons1, M J de Boer, M J van den Brand
1Thoraxcenter, Rotterdam, The Netherlands.
Insights
Chimeric 7E3 Fab effectively inhibits platelet aggregation, significantly reducing myocardial infarction and facilitating percutaneous transluminal coronary angioplasty in patients with refractory unstable angina.
Area of Science:
- Cardiology
- Pharmacology
- Thrombosis
Background:
- Refractory angina patients face high thrombotic complication risks.
- Chimeric 7E3 Fab blocks platelet glycoprotein IIb/IIIa receptors, inhibiting aggregation.
Purpose of the Study:
- To evaluate if potent platelet inhibition by c7E3 Fab reduces complications in refractory angina.
- To assess the safety and efficacy of c7E3 Fab in patients undergoing PTCA.
Main Methods:
- 60 patients with unstable angina randomized to c7E3 Fab or placebo.
- c7E3 Fab administered as a bolus followed by infusion during PTCA.
- Platelet function, bleeding time, and clinical events were monitored.
Main Results:
- Significantly fewer major events (1 vs 7) in the c7E3 Fab group compared to placebo.
- Reduced ischemia during study drug infusion in the c7E3 Fab group (9 vs 16 patients).
- Improved TIMI flow and lesion characteristics observed with c7E3 Fab treatment.
Conclusions:
- Combined therapy with c7E3 Fab, heparin, and aspirin is safe.
- Effective blockade of GPIIb/IIIa receptors reduces myocardial infarction and facilitates PTCA.
- Pilot study results support c7E3 Fab's role in managing refractory unstable angina.
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.