EFFECTS OF PLATELET GLYCOPROTEIN IIB IIIA BLOCKADE WITH TIROFIBAN ON ADVERSE CARDIAC EVENTS IN PATIENTS WITH UNSTABLE ANGINA OR ACUTE MYOCARDIAL-INFARCTION UNDERGOING CORONARY ANGIOPLASTY/

Background Adverse cardiovascular events associated with thrombotic oc clusion occur in 4% to 12.8% of patients after coronary angioplasty. R ecently, potent antiplatelet agents have been used to reduce those thr ombotic complications. Tirofiban is a highly selective, short-acting i nhibitor of fibrinogen binding to platelet glycoprotein (GP) IIb/IIIa that inhibits ex vivo platelet aggregation in response to a variety of agonists. Methods and Results The RESTORE trial (Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis) was a randomized, doub le-blind, placebo-controlled trial oi tirofiban ban in patients underg oing coronary interventions (balloon angioplasty or directional athere ctomy) within 72 hours of presentation with an acute coronary syndrome (unstable angina pectoris or acute myocardial infarction). The end po ints of the study were death from any cause, myocardial infarction, co ronary bypass surgery due to angioplasty failure or recurrent ischemia , repeat target-vessel angioplasty for recurrent ische- mia, and inser tion of a stent due to actual or threatened abrupt closure of the dila ted artery, and the primary end point was a composite representing the occurrence of any of these events. The prespecified primary hypothesi s of the study was that tirofiban, administered as a bolus of 10 mu g/ kg over a S-minute period and followed by a 36-hour infusion of 0.15 m u g.kg(-1).min(-1), would result in a reduction in the 30-day composit e end point compared with placebo. Patients (n=2139) who were already receiving treatment with aspirin and heparin were randomized to receiv e tirofiban or placebo. The primary composite end point at 30 days was reduced from 12.2% in the placebo group to 10.3% in the tirofiban gro up, a 16% relative reduction (P=.160). However, 2 days after angioplas ty, the tirofiban group had a 38% relative reduction in the composite end point (P less than or equal to.005), and at 7 days there was a 27% relative reduction (P=.022), largely because of a reduction in nonfat al myocardial infarction and the need for repeat angioplasty. When rep eat angioplasty or coronary artery bypass surgery procedures were incl uded in the composite only if performed on an urgent or emergency basi s, the composite 30-day event rates were 10.5% for the placebo group a nd 8.0% for the tirofiban group, a relative reduction of 24% (P=.052). Major bleeding, including transfusion, was not significantly differen t between the two groups (3.7% in the placebo group and 5.3% in the ti rofiban group; P=.096). When the Thrombolysis In Myocardial Infarction (TIMI) criteria for major bleeding were used, the incidence was 2.1% in the placebo group compared with 2.4% in the tirofiban group (P=.662 ). Thrombocytopenia was similar in the placebo and tirofiban groups (0 .9% for the placebo group versus 1.1% for the tirofiban group; P=.709) . Conclusions In patients undergoing coronary angioplasty for acute co ronary syndromes, tirofiban protects against early adverse cardiac eve nts related to thrombotic closure. At 30 days, however, the reduction in adverse cardiac events was no longer statistically significant. The bleeding observed with tirofiban was not statistically different from that observed with placebo.