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 ¹¹¹In-platelet content and weights. Thrombus weight and platelet deposition were significantly reduced by PD0348292 at 0.4 (49±79 mg and 110±145x10⁶/cm²), 0.9 (5±6 mg and 107±128x10⁶/cm²), 4.3 mg/kg (0±0 mg and 87±125x10⁶/cm²), and PD348292 plus aspirin (20±40 mg and 157±70x10⁶/cm²) compared with vehicle (402±226 mg; 584±454x10⁶/cm²). Despite prolonging bleeding times and inhibiting platelet aggregation, neither aspirin (567±683 mg and 533±622x10⁶/cm²), clopidogrel (404±349 mg and 178±101x10⁶/cm²), nor aspirin plus clopidogrel (247±261 mg and 231±266x10⁶/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.