Monitoring of Argatroban in ARG310 Study: Potential Recommendations for its Use in Interventional Cardiology

Abstract

Argatroban is a peptidomimetic synthetic direct thrombin inhibitor with reversible and specific properties resulting in predictable anticoagulant effects. Usually, argatroban therapy is monitored by the activated clotting time (ACT) or activated partial thromboplastin time (aPTT). While other global clotting tests for the monitoring of anticoagulants are useful, their applicability to antithrombin agents (particularly of argatroban at higher dosages) is rather questionable. In this study, we sought to compare the argatroban anticoagulant levels in patients undergoing percutaneous transluminal angioplasty (PTCA) and stenting procedures, utilizing both functional and absolute quantitation methods. Argatroban produced a comparable increase of ACT and HMT, 5 to 10 minutes after administration. The level of anticoagulation achieved (400-450 seconds with ACT and HMT) following a slow bolus of argatroban (350 aglkg) was maintained throughout the procedure using 25 jtg/kg/min infusion. Following discontinuation of argatroban at the end of the procedure, the ACTs and HMTs showed a comparable progressive reduction in the anticoagulant response, which reflected the elimination of argatroban 2 to 3 hours after the procedure. No significant differences between the three methods (Hemotec, Hemochron, and HMT) were noted at any given sampling time. Argatroban dosage at 350 Ag/kg intravenous slow bolus followed by 25 Ag/kg/min infusion was adequate to perform PTCA and stenting procedures. There was no incidence of bleeding complications. Absolute quantitation of argatroban levels in patient plasmas by a newly developed HPLC method was found to be quite comparable with the ecarin clotting time (ECT) results. The ECT system was found to be less sensitive when compared to other tests, and therefore, could be used as a point-of-care test during the PTCA/stenting procedures to monitor argatroban.