INTERNATIONAL, RANDOMIZED, CONTROLLED TRIAL OF LAMIFIBAN (A PLATELET GLYCOPROTEIN IIB IIIA INHIBITOR), HEPARIN, OR BOTH IN UNSTABLE ANGINA/

Background-Unstable angina and non-Q-wave myocardial infarction involv e coronary arterial plaque rupture, platelet activation, and thrombus formation. This study tested the benefit of different doses of lamifib an (a platelet IIb/IIIa antagonist) alone and in combination with hepa rin in patients with these conditions to select the most promising lam ifiban regimen for subsequent evaluation. Methods and Results-At 273 h ospitals in 20 countries, 2282 patients were randomly assigned to lami fiban (2x2 factorial design: low-dose [1 mu g/min] with and without he parin versus high-dose [5 mu g/min] with and without heparin) or to st andard therapy (placebo and heparin). All patients received aspirin. T he composite primary end point of death or nonfatal myocardial infarct ion at 30 days occurred in 11.7% of those receiving standard therapy, 10.6% receiving low-dose lamifiban, and 12.0% receiving high-dose lami fiban (P=0.668). By 6 months, this composite was lowest for those assi gned to low-dose lamifiban (P=0.027) and intermediate for those assign ed to high-dose lamifiban (P=0.450) compared with control (13.7%, 16.4 %, and 17.9%, respectively). Compared with control, the combination of high-dose lamifiban and heparin resulted in more intermediate or majo r bleeding (12.1% versus 5.5%; P=0.002) and a similar rate of ischemic events. Conversely, low-dose lamifiban and heparin yielded similar bl eeding rates as in the control group but fewer ischemic events at 6 mo nths (12.6% versus 17.9%; P=0.025). Conclusions-In unstable angina and non-Q-wave infarction, platelet IIb/IIIa antagonism with lamifiban re duces adverse ischemic events at 6 months beyond that of aspirin and h eparin therapy. The role of conjunctive heparin remains uncertain but appears more favorable with low-dose IIb/IIIa antagonism. Larger-scale study is needed to more reliably estimate these effects.