PARAGON-B

Background

Small-molecule inhibitors of platelet glycoprotein IIb/IIIa reduce the rate of death or myocardial infarction (MI) among patients presenting with acute coronary syndromes without persistent ST-segment elevation, but their effects may depend upon plasma concentrations. We tested whether the use of a simple dosing algorithm intended to achieve steady-state lamifiban concentrations of 18 to 42 ng/mL would improve clinical outcomes when added to standard care.

Methods and Results

We randomized 5225 patients at 389 centers in 29 countries to receive a bolus and up to 72-hour infusion of lamifiban or placebo, adjusted for estimated creatinine clearance and weight, with aspirin and heparin. The primary endpoint was the composite of death, MI, or severe, recurrent ischemia at 30 days. Samples for lamifiban concentrations were obtained just before the infusion ended. Baseline characteristics did not differ significantly by treatment. The primary endpoint occurred in 11.8% of lamifiban-treated patients and in 12.8% of placebo-treated patients (odds ratio, 0.914; 95% CI, 0.769 to 1.087; P=0.329). In the subgroup who underwent percutaneous intervention, lamifiban was associated with a reduction in the primary endpoint (11.6% vs. 18.5%). Bleeding was more common in lamifiban-treated patients, but the incidence of intracranial hemorrhage was not increased. In all, 87% of patients had a plasma lamifiban concentration >20 ng/mL at steady-state, but their outcomes did not differ from those with a lower concentration.

Conclusions

Lamifiban showed no significant effects on the incidence of clinical outcomes in patients with non-ST-elevation acute coronary syndromes, despite achievement of adequate plasma concentrations.