Initial experience with factor‐Xa inhibition in percutaneous coronary intervention: the XaNADU‐PCI Pilot

Background: Direct factor (F)Xa inhibition is an attractive method to limit thrombotic complications during percutaneous coronary intervention (PCI). Objectives: To investigate drug levels achieved, effect on coagulation markers, and preliminary efficacy and safety of several doses of DX‐9065a, an intravenous, small molecule, direct, reversible FXa inhibitor during PCI. Patients and methods: Patients undergoing elective, native‐vessel PCI (n= 175) were randomized 4 : 1 to open‐label DX‐9065a or heparin in one of four sequential stages. DX‐9065a regimens in stages I–III were designed to achieve concentrations of > 100 ng mL−1, > 75 ng mL−1, and > 150 ng mL−1. Stage IV used the stage III regimen but included patients recently given heparin. Results: At 15 min median (minimum) DX‐9065a plasma levels were 192 (176), 122 (117), 334 (221), and 429 (231) ng mL−1in stages I–IV, respectively. Median whole‐blood international normalized ratios (INRs) were 2.6 (interquartile range 2.5, 2.7), 1.9 (1.8, 2.0), 3.2 (3.0, 4.1), and 3.8 (3.4, 4.6), and anti‐FXa levels were 0.36 (0.32, 0.38), 0.33 (0.26, 0.39), 0.45 (0.41, 0.51), and 0.62 (0.52, 0.65) U mL−1, respectively. Stage II enrollment was stopped (n= 7) after one serious thrombotic event. Ischemic and bleeding events were rare and, in this small population, showed no clear relation to DX‐9065a dose. Conclusions: Elective PCI is feasible using a direct FXa inhibitor for anticoagulation. Predictable plasma drug levels can be rapidly obtained with double‐bolus and infusion DX‐9065a dosing. Monitoring of DX‐9065a may be possible using whole‐blood INR. Direct FXa inhibition is a novel and potentially promising approach to anticoagulation during PCI that deserves further study.