Abstract 2781: Argatroban Anticoagulation for PCI: The E04 European Multi-Center Study
Background —Argatroban is an attractive drug for cardiology because it has a fast onset and offset of anticoagulation, and is hepatically excreted. Argatroban received approval for PCI in patients (pts) with heparin-induced thrombocytopenia (HIT) in the U.S. in 2002. However, data about argatroban in the current PCI setting is limited.
Methods –The E04 trial, an open-label, parallel-group, multiple-dose study, included 140 pts undergoing PCI. Pts were randomly assigned to three argatroban- (250, 300 or 350 ìg/kg as a bolus injection before PCI, followed by 15, 20 or 25 ìg/kg/min infusion until the end of the procedure) and one unfractionated heparin (UFH)-treated groups (70 –100 IU/kg as a bolus injection). Efficacy endpoints were the proportion of pts reaching the minimum target ACT (250 sec.) after the initial bolus injection of each anticoagulant; ACT time-course during PCI; number of additional bolus injections; composite incidence of all-cause death, myocardial infarction (MI) and urgent revascularization until Day 30; and incidence of hemorrhagic events during the hospital stay.
Results —Argatroban dose-dependently prolonged ACT. Significantly (p < 0.01) more pts reached the minimum target ACT after the initial bolus injection with 86.1%, 89.5% and 96.8% in the low, middle and high dose argatroban groups, respectively, compared to 45.5% in the UFH group. Time to start of PCI after reaching minimum target ACT was significantly (p < 0.01) shortened in the argatroban groups compared to UFH. Composite incidences of death, MI and urgent revascularization were 2.8%, 0.0%, 3.2% and 3.0% in the low, middle and high dose argatroban groups, and the UFH group, respectively (n.s.). Major bleeding was observed only in the UFH group (3.0%), and minor bleeding occurred in the high dose argatroban (3.2%) and the UFH group (6.1%).
Conclusions —Argatroban had an adequate anticoagulant effect. More pts reached the minimum target ACT in the argatroban groups than in the UFH group. This resulted in a reduced time to start PCI. Although the sample size was too small to conclude an effect on clinical outcome, the results suggest that argatroban is a safe and effective anticoagulant for PCI in the current clinical setting.