Iliac Venous Stenting: Antithrombotic efficacy of PD0348292, an oral direct factor xa inhibitor, compared with antiplatelet agents in pigs

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±145 × 10 ⁶/cm ²), 0.9 (5±6 mg and 107±128X10 ⁶/cm ²), 4.3 mg/kg (0±0 mg and 87±125 × 10 ⁶/cm ²), and PD348292 plus aspirin (20±40 mg and 157±70 × 10 ⁶/cm ²) compared with vehicle (402±226 mg; 584±454 × 10 ⁶/cm ²). Despite prolonging bleeding times and inhibiting platelet aggregation, neither aspirin (567±683 mg and 533±622 × 10 ⁶/cm ²), clopidogrel (404±349 mg and 178±101 × 10 ⁶/cm ²), nor aspirin plus clopidogrel (247±261 mg and 231±266 × 10 ⁶/cm ²) 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 P ₂Y ₁₂ receptor activation.