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.


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.
McBane
Robert D
RD
Section of Hematology Research, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA. mcbane.robert@mayo.edu
Leadley
Robert J
RJ
Baxi
Sangita M
SM
Karnicki
Krzysztof
K
Wysokinski
Waldemar
W
D000284:Administration, Oral; D017130:Angioplasty / Q000379:methods; D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D000077144:Clopidogrel; D003251:Constriction, Pathologic / Q000517:prevention & control; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D007084:Iliac Vein / Q000601:surgery; D011300:Preoperative Care / Q000379:methods; D011336:Probability; D011728:Pyridones / Q000008:administration & dosage*; D011759:Pyrrolidines / Q000008:administration & dosage*; D011897:Random Allocation; D012016:Reference Values; D015607:Stents; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome; D014654:Vascular Patency / Q000187:drug effects; D020246:Venous Thrombosis / Q000188:drug therapy* / Q000601:surgery
C523986:N-(4-chlorophenyl)-N-(2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)-4-methoxypyrrolidiine-1,2-dicarboxamide; D011728:Pyridones; D011759:Pyrrolidines; D000990:Antithrombin III; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin