Iliac venous stenting: antithrombotic efficacy of PD0348292, an oral direct Factor Xa inhibitor, compared with antiplatelet agents in pigs

Abstract

Objective: The clinical use of venous stents is increasing dramatically. Although antiplatelet agents are required for arterial stent patency, optimal thrombo-prophylaxis after venous stenting remains undefined. To address this issue, PD0348292, a direct Factor Xa inhibitor, was compared with antiplatelet therapy in a porcine venous stent model.

Methods and results: Four hours before stent deployment, pigs (n=5 to 6 per group) received oral PD0348292 at 0.4, 0.9, 4.3 mg/kg, or 0.4 mg/kg plus aspirin (325 mg). Aspirin, clopidogrel (75 mg), aspirin plus clopidogrel, or vehicle (n=10) were administered daily for 2 days before the procedure. Two hours after stent placement, thrombi were quantified by autologous (111)In-platelet content and weights. Thrombus weight and platelet deposition were significantly reduced by PD0348292 at 0.4 (49+/-79 mg and 110+/-145x10(6)/cm2), 0.9 (5+/-6 mg and 107+/-128x10(6)/cm2), 4.3 mg/kg (0+/-0 mg and 87+/-125x10(6)/cm2), and PD348292 plus aspirin (20+/-40 mg and 157+/-70x10(6)/cm2) compared with vehicle (402+/-226 mg; 584+/-454x10(6)/cm2). Despite prolonging bleeding times and inhibiting platelet aggregation, neither aspirin (567+/-683 mg and 533+/-622x10(6)/cm2), clopidogrel (404+/-349 mg and 178+/-101x10(6)/cm2), nor aspirin plus clopidogrel (247+/-261 mg and 231+/-266x10(6)/cm2) significantly decreased stent thrombosis.

Conclusions: PD0348292 completely inhibited thrombosis after venous stenting. Platelet accretion in these venous thrombi appear to involve pathways distinct from arachidonate metabolism or ADP P2Y12 receptor activation.