Randomized, placebo-controlled trial of titrated intravenous lamifiban for acute coronary syndromes.
BACKGROUND
Platelet glycoprotein IIb/IIIa inhibitors reduce the rate of death or myocardial infarction among patients with acute coronary syndromes without persistent ST-segment elevation, but their effects may depend on plasma concentrations. We tested whether the addition of lamifiban, titrated to achieve target plasma concentrations, to standard care would improve clinical outcomes.


RESULTS
We randomized 5225 patients at 389 centers in 29 countries to receive a bolus and </=72-hour infusion of lamifiban or placebo, adjusted for renal function, with aspirin and heparin. The primary end point was the composite of death, myocardial infarction, or severe, recurrent ischemia at 30 days. Baseline characteristics did not differ significantly by treatment. The primary end point occurred in 11.8% of lamifiban-treated patients and in 12.8% of placebo-treated patients (OR, 0.914; 95% CI, 0.769 to 1.087; P=0.329). Bleeding was more common in lamifiban-treated patients, but intracranial hemorrhage was not increased. Among the subgroup who had plasma lamifiban concentrations measured, 91% had a concentration >18 ng/mL at steady state, but their outcomes did not differ from those with lower concentrations.


CONCLUSIONS
Lamifiban showed no significant effects on clinical outcomes in patients with non-ST-elevation acute coronary syndromes, despite achievement of adequate plasma concentrations.
D000085:Acetates / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use; D000208:Acute Disease; D000368:Aged; D003327:Coronary Disease / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D004311:Double-Blind Method; D023381:Endpoint Determination; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D006801:Humans; D015994:Incidence; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000032:analysis / Q000097:blood / Q000627:therapeutic use; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013577:Syndrome; D017186:Titrimetry; D016896:Treatment Outcome; D014443:Tyrosine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use
D000085:Acetates; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; C084062:lamifiban