The aptamer ARC1779 is a potent and specific inhibitor of von willebrand factor mediated ex vivo platelet function in acute myocardial infarction

ARC1779 is an aptamer, which blocks binding of the von Willebrand Factor (VWF) A1 domain to platelet GPIb receptors. VWF is increased in the elderly an in the setting of acute myocardial infarction (AMI), as reflected by increased shear-dependent platelet function. We hypothesized that ARC1779 concentration-dependently inhibits ex vivo platelet function, and that this concentration effect relationship may be shifted in patients with AMI. We studied ex vivo dose response curves for ARC1779 on VWF activity, shear-dependent platelet function, and agonist-induced platelet aggregation. We included patients with AMI on standard treatment (n = 40), young (n = 20) and elderly controls (n = 20) in this ex vivo dosing study. AMI patients displayed ∼2-fold increased plasma levels of VWF activity as compared to controls. ARC1779 inhibited VWF activity (IC90: ∼3–4 µg/mL) and shear dependent platelet function (Platelet Function Analyzer (PFA-100), IC50: ∼0.5–0.9 µg/mL and Cone and Plate Analyzer (CPA), IC50: ∼0.1–0.4 µ...