Tissue factor pathway inhibitor as a candidate coating material for drug eluting stents to prevent restenosis

TFPI (tissue factor pathway inhibitor) is a Kunitz-type protease inhibitor, which blocks factor VIIa/tissue factor and factor Xa. TFPI has an anti-proliferative effect on cultured smooth muscle cells, as well as an anti-thrombotic effect. In the present study, the iliac artery of rabbits was experimentally injured with a Cutting Balloon™ and then the effects of TFPI were examined, rTFPI was delivered locally via a Pulse Spray® catheter (40 μg/ml once per minute, to a total amount of 200 μg). Immediately after delivery, 241.7±123.5 ng of rTFPI were present in the injured vessel walls. Furthermore, 2.6±1.6 ng of rTFPI remained at the delivery sites. Surprisingly, at 48% of the cut media sites, rTFPI remained detectable on the injured media until 7 days after angioplasty. The degree of thrombosis and neointimal formation after 4 weeks was significantly reduced compared to the control group (P=0.0074 and 0.030, respectively). However, when Palmaz-Schatz stents were implanted, fibrin thrombi formed more frequently close to the stent struts in both groups. In conclusion, local delivery of rTFPI might be useful for prevention of restenosis because of its anti-inflammatory effects. TFPI could therefore be a candidate material for coating stents, which would then be locally eluted.