IMPACT II Results: Balloon Angioplasty/Bail-out Stenting 9.1% 10.0% 11.6% 4.4% 4.7% 4.5% 1.6%  (P=ns) 30 Day Death/MI/UTVR 2.5%  (P=0.035) Major TIMI Bleeding % events The IMPACT II investigators. Lancet. 1997; 349: 1432-1428..

IMPACT II Ex vivo platelet aggregation for eptifibatide 135/0.75 Citrate vs PPACK Targeted Inhibition PPACK Citrate % Inhibition versus baseline Time (hours after start of infusion) PRIDE: EX VIVO PLATELET AGGREGATION INHIBITION WITH EPTIFIBATIDE 135/0.75 USING CITRATE VS. PPACK The choice of anticoagulant used in the assay dramatically impacted the degree of inhibition of ADP-induced platelet aggregation that was seen with eptifibitide. Assays employing sodium citrate consistently yielded higher estimates of platelet inhibition than assays using PPACK, which are more representative of the in vivo platelet aggregation environment. The results from PRIDE show that even the higher dose of eptifibitide used in IMPACT II (135g/kg and 0.75g/kg/min), which was selected based on assays in citrate-anticoagulated blood, did not achieve optimal levels of inhibition of platelet aggregation in blood anticoagulated with PPACK.

IMPACT II Key Findings In the era of balloon angioplasty and bail-out stenting, eptifibatide dosed as a 135 µg/kg bolus and 0.5 µg/kg/min infusion for 20-24 hours significantly, although moderately, reduced the incidence of death, MI, or urgent revascularization during drug infusion and maintained that effect over time Use of sodium citrate anticoagulant during initial platelet aggregation inhibition studies resulted in an overestimation of in vivo platelet aggregation inhibition achieved with the doses studied in IMPACT II Clearly, eptifibatide was under-dosed in IMPACT II