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Randomized, Placebo-Controlled Study of Lamifiban with Thrombolytic Therapy for the Treatment of Acute Myocardial
Moliterno1, Harrington, Califf
1Department of Cardiology and the Joseph J. Jacobs Center for Thrombosis and Vascular Biology, The Cleveland Clinic Foundation, Cleveland, OH and Department of Cardiology, F-25, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195.
Insights
Thrombolytic therapy improves acute myocardial infarction survival. Adding Lamifiban, a glycoprotein IIb/IIIa antagonist, may enhance coronary artery reperfusion and patient outcomes in this critical condition.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Thrombolytic therapy is crucial for acute myocardial infarction (AMI) survival, with early coronary reperfusion (TIMI grade 3 flow) linked to highest survival rates.
- Despite advancements, many AMI patients do not achieve adequate coronary perfusion with thrombolysis alone.
- Aspirin's antiplatelet effect is weaker than glycoprotein IIb/IIIa antagonists, which target the final pathway of platelet aggregation.
Purpose of the Study:
- To determine the optimal dose of Lamifiban, a nonpeptide glycoprotein IIb/IIIa receptor antagonist, for safety and efficacy when used with thrombolytic therapy in AMI.
- To evaluate Lamifiban's potential to improve coronary arterial patency and clinical outcomes in AMI patients.
Main Methods:
- The Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) study is a randomized, placebo-controlled, phase II trial.
- The study involves 400 patients with AMI receiving thrombolysis.
- Key assessments include 90-minute angiography, platelet aggregation, continuous electrocardiography, and clinical outcomes.
Main Results:
- Early experimental studies and Phase I/II data suggest Lamifiban is safe and effective in restoring coronary patency when combined with thrombolysis.
- The PARADIGM study aims to provide crucial insights into optimal Lamifiban dosing for Phase III trials by analyzing angiographic, electrophysiologic, and clinical data.
Conclusions:
- Lamifiban shows promise as an adjunct to thrombolytic therapy for improving coronary perfusion in AMI.
- The PARADIGM study is essential for establishing the optimal dose of Lamifiban for large-scale clinical evaluation in AMI treatment.
Abstract:
The benefits of thrombolytic therapy in the treatment of acute myocardial infarction are incontrovertible. Large-scale studies combining angiographic and clinical end-points have demonstrated a perfusion-mortality relationship, with the highest survival rate among patients with early restoration of TIMI grade 3 coronary arterial flow. Despite advances in thrombolytic strategies, a substantial number of patients fail to rapidly achieve and maintain adequate coronary perfusion with thrombolysis. Conjunctive therapy with aspirin has proven useful in thrombolytic regimens, likely countering the heightened platelet activity central to acute coronary syndromes. The antiplatelet effect of aspirin is relatively weak compared with that of glycoprotein IIb/IIIa platelet receptor antagonists, which block the final common pathway of platelet aggregation. Lamifiban is a nonpeptide glycoprotein IIb/IIIa receptor antagonist. In early experimental studies, Lamifiban in combination with thrombolytic therapy has been shown to effectively restore coronary arterial patency, and phase I and phase II data have shown its use to be safe. To determine the optimal dose with regard to safety and efficacy of Lamifiban to be used with thrombolytic therapy in a large-scale trial, a phase II study is underway. The Platelet Aggregation Receptor Antagonist Dose Investigation and Reperfusion Gain in Myocardial Infarction (PARADIGM) study is a randomized, placebo-controlled study of Lamifiban in 400 patients receiving thrombolysis as treatment for acute myocardial infarction. By studying 90-minute angiography, platelet aggregation, continuous electrocardiography, and clinical outcome in PARADIGM, important insights will be obtained to determine the optimal dose of Lamifiban for phase III study. We provide the background and rationale for the study of Lamifiban in PARADIGM and other ongoing studies in acute coronary syndromes.
