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

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

Research output: Contribution to journalArticle

16 Scopus citations

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±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.

Original languageEnglish (US)
Pages (from-to)413-418
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume28
Issue number3
DOIs
StatePublished - Mar 1 2008

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Keywords

  • Aspirin
  • Clopidogrel
  • Coagulation factor Xa
  • Stent
  • Venous thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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