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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:413.)
© 2008 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Iliac Venous Stenting

Antithrombotic Efficacy of PD0348292, an Oral Direct Factor Xa Inhibitor, Compared With Antiplatelet Agents in Pigs

Robert D. McBane, II; Robert J. Leadley, Jr; Sangita M. Baxi; Krzysztof Karnicki; Waldemar Wysokinski

From the Section of Hematology Research (R.D.M., K.K., W.W.), Mayo Clinic, Rochester, Minn; Cardiovascular, Metabolic, and Endocrine Diseases Biology (R.J.L., S.M.B.), Pfizer Global Research and Development, Ann Arbor, Mich; and the Division of Cardiology (R.D.M., W.W.), Mayo Clinic, Rochester, Minn.

Correspondence to Robert D. McBane II, MD, Division of Cardiovascular Medicine, Mayo Clinic, 200 First Street, Rochester, MN, 55905. E-mail mcbane.robert{at}mayo.edu

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 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.

In a porcine model of iliac venous stenting, the oral direct Factor Xa inhibitor PD0348292 promptly and completely inhibited thrombosis. Aspirin or clopidogrel had no significant effect on stent thrombosis, indicating that platelet accretion in these thrombi appear to involve pathways distinct from arachidonate metabolism or ADP P₂Y₁₂ receptor activation.

Key Words: coagulation factor Xa • aspirin • clopidogrel • stent • venous thrombosis