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. The RESTORE Investigators. Randomized Efficacy Study of Tirofiban for Outcomes and REstenosis.
BACKGROUND: Adverse cardiovascular events associated with thrombotic occlusion occur in 4% to 12.8% of patients after coronary angioplasty. Recently, potent antiplatelet agents have been used to reduce those thrombotic complications. Tirofiban is a highly selective, short-acting inhibitor 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, double-blind, placebo-controlled trial of tirofiban in patients undergoing coronary interventions (balloon angioplasty or directional atherectomy) within 72 hours of presentation with an acute coronary syndrome (unstable angina pcctoris or acute myocardial infarction). The end points of the study were death from any cause, myocardial infarction, coronary bypass surgery due to angioplasty failure or recurrent ischemia, repeat target-vessel angioplasty for recurrent ischemia, and insertion of a stent due to actual or threatened abrupt closure of the dilated artery, and the primary end point was a composite representing the occurrence of any of these events. The prespecified primary hypothesis of the study was that tirofiban, administered as a bolus of 10 microg/kg over a 3-minute period and followed by a 36-hour infusion of 0.15 microg x kg(-1) x min(-1), would result in a reduction in the 30-day composite end point compared with placebo. Patients (n=2139) who were already receiving treatment with aspirin and heparin were randomized to receive 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 group, a 16% relative reduction (P=.160). However, 2 days after angioplasty, the tirofiban group had a 38% relative reduction in the composite end point (P< or =.005), and at 7 days there was a 27% relative reduction (P=.022), largely because of a reduction in nonfatal myocardial infarction and the need for repeat angioplasty. When repeat angioplasty or coronary artery bypass surgery procedures were included in the composite only if performed on an urgent or emergency basis, the composite 30-day event rates were 10.5% for the placebo group and 8.0% for the tirofiban group, a relative reduction of 24% (P=.052). Major bleeding, including transfusion, was not significantly different between the two groups (3.7% in the placebo group and 5.3% in the tirofiban 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 coronary syndromes, tirofiban protects against early adverse cardiac events 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.