Newer antiplatelet agents in acute coronary syndromes

Aspirin is accepted as standard therapy in the management of acute coronary syndromes, but has significant limitations, including intolerance, allergy, resistance, peptic ulceration, and intracranial hemorrhage. Recent trials involving approximately 18,000 patients with unstable angina have investigated the efficacy and safety of glycoprotein IIb/IIIa receptor antagonists, which block the final common pathway of platelet aggregation. The Platelet Receptor Inhibition in Ischemic Syndrome Management (PRISM) trial compared tirofiban with heparin and found a 33% reduction in the composite end point of death, myocardial infarction, or refractory ischemia at 48 hours. In the Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms (PRISM-PLUS) trial, patients were randomly assigned to receive either heparin, tirofiban, or both. At 7 days, the patients who had received heparin and tirofiban had a 34% lower incidence of the composite end point of death, myocardial infarction, or refractory ischemia than those treated with heparin alone. The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial randomly assigned patients to receive either eptifibatide or placebo. At 30 days, the rate of death or myocardial infarction was reduced by 9.6% in the eptifibatide group compared with the placebo group. In the Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON) trial, patients were randomly assigned to receive either low- or high-dose lamifiban with or without heparin, or heparin alone. There were no differences between the treatment groups at 30 days, but at 6 months the patients randomly assigned to receive low-dose lamifiban had a 23% lower incidence of death or myocardial infarction, perhaps because of long-term passivation of the plaque. Overall, IIb/IIIa antagonists have been shown to be safe and beneficial in patients with unstable angina, particularly during the infusion period. However, there remain a number of unanswered questions concerning treatment with these agents, such as the appropriate dosing regimens and the safety and efficacy of combining intravenous antiplatelet therapy with other agents such as low-molecular-weight heparin, thrombolytic agents, and oral agents.