By Mikel Rothenberg, MD
Platelet Receptor Antagonists in Ischemic Heart Disease
The final step in platelet aggregation involves the platelet membrane receptor glycoprotein (GP) IIb/IIIa. A recent study by Theroux et al was designed to evaluate the potential of lamifiban, an antagonist of GP IIb/IIIa, in the management of unstable angina. Three hundred sixty-five patients with unstable angina were randomized to an infusion of 1, 2, 4, or 5 mcg/min of lamifiban or placebo. Treatment was administered for 72-120 hours. Concomitant aspirin was administered to all patients, and heparin to 28% of patients. Lamifiban, at all dose ranges, reduced the risk of death, nonfatal myocardial infarction, and the need for an urgent coronary artery bypass during the infusion period. Higher doses had better responses, but all patients who received the drug had significantly better outcomes than those who received placebo. At one month, death or nonfatal infarction occurred in 8.1% of patients with placebo and in 2.5% of patients with the two higher doses. Bleeding times were significantly prolonged; major (but neither life-threatening nor intracranial) bleeding occurred in 0.8% of patients with placebo and 2.9% with lamifiban. The authors conclude: "The nonpeptide GP IIb/IIIa antagonist lamifiban protected patients with unstable angina from severe ischemic events during a three- to five-day infusion and reduced the incidence of death and infarction at one month, suggesting considerable promise for this new therapeutic approach." (Theroux P, et al. Platelet membrane receptor glycoprotein IIb/IIIa antagonism in unstable angina. The Canadian Lamifiban Study. Circulation 1996;4:899-905.)
The most interesting finding in the above study was the fact that the benefit persisted well beyond the infusion period. If this "pans out," then we may be giving this (or a similar) drug in the ED, or maybe even in the field along with magnesium, IV nitroglycerine, thrombolytics, leuko triene receptor inhibitors, and who knows what else? A very exciting time in acute cardiovascular pharmacology!