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.