INHIBITION OF PLATELET GLYCOPROTEIN IIB IIIA WITH EPTIFIBATIDE IN PATIENTS WITH ACUTE CORONARY SYNDROMES/

Background Aggregation of platelets is the pathophysiologic basis of t he acute coronary syndromes. Eptifibatide, a synthetic cyclic heptapep tide, is a selective high-affinity inhibitor of the platelet glycoprot ein IIb/IIIa receptor, which is involved in platelet aggregation. We t ested the hypothesis that inhibition of platelet aggregation with epti fibatide would have an incremental benefit beyond that of heparin and aspirin in reducing the frequency of adverse outcomes in patients with acute coronary syndromes who did not have persistent ST-segment eleva tion. Methods Patients who had presented with ischemic chest pain with in the previous 24 hours and who had either electrocardiographic chang es indicative of ischemia (but not persistent ST-segment elevation) or high serum concentrations of creatine kinase MB isoenzymes were enrol led in the study. They were randomly assigned, in a double-blind manne r, to receive a bolus and infusion of either eptifibatide or placebo, in addition to standard therapy, for up to 72 hours (or up to 96 hours , if coronary intervention was performed near the end of the 72-hour p eriod). The primary end point was a composite of death and nonfatal my ocardial infarction occurring up to 30 days after the index event. Res ults A total of 10,948 patients were enrolled between November 1995 an d January 1997. As compared with the placebo group, the eptifibatide g roup had a 1.5 percent absolute reduction in the incidence of the prim ary end point (14.2 percent, vs. 15.7 percent in the placebo group; P = 0.04). The benefit was apparent by 96 hours and persisted through 30 days. The effect was consistent in most major subgroups except for wo men (odds ratios for death or nonfatal myocardial infarction, 0.8 [95 percent confidence interval, 0.7 to 0.9] in men, and 1.1 [0.9 to 1.3] in women). Bleeding was more common in the eptifibatide group, althoug h there was no increase in the incidence of hemorrhagic stroke. Conclu sions inhibition of platelet aggregation with eptifibatide reduced the incidence of the composite end point of death or nonfatal myocardial infarction in patients with acute coronary syndromes who did not have persistent ST-segment elevation. (N Engl J Med 1998;339:436-43.) (C)19 98, Massachusetts Medical Society.