Integrilin Dose Optimization Using Cone Plate Analyzer – What Have We Learned Thus Far

Objectives: To assess platelet inhibition by cone and plate analyzer (CPA) in patients with acute coronary syndromes (ACS) receiving eptifibatide (Integrilin). Background: With the current use of glycoprotein IIb/IIIa (GP-IIb/IIIa) inhibitors during ACS and percutaneous coronary interventions (PCI), the need to measure platelet activity and optimize dosing became apparent. CPA is a novel technique to assess platelet activity in high shear stress conditions, mimicking arterial flow. Method: 40 consecutive patients with ACS received eptifibatide [2 intravenous boluses (180 µg/kg each) spaced 10 min apart, and subsequently a maintenance drip (2 µg/kg/min)]. All patients received aspirin, clopidogrel and unfractionated heparin or enoxaparin in conventional doses. Blood was obtained at baseline, 30 min and 3 h, after eptifibatide initiation, and was sent out for CPA core lab, blinded to patient therapy, characteristics, and sampling time. Results: At 30 min and 3 h only 45 and 60% of patients, respectively, reached GP-IIb/IIIa blockade of ≧95%. 25 and 15%, respectively, had <85% GP-IIb/IIIa blockade. No demographic, clinical, or laboratory predictors for eptifibatide resistance could be identified. Conclusion: <85% GP-IIb/IIIa blockade occurs in a high proportion of patients with ACS treated with eptifibatide. The clinical significance of this phenomenon, and the optimal way to assess and treat it warrant additional research. It is essential, however, to measure platelet activity or GP-IIb/IIIa occupancy in response to therapy, since no demographic, clinical, and laboratory predictors of eptifibatide refractoriness can be identified at this time at the bedside.