Intimal proliferation at the interface between prosthetic material and tissue is an intrinsic phenomenon of stenting and the major cause of insufficiency of the transjugular intrahepatic
portosystemic shunt (
TIPS). For its prevention, a randomized study was performed comparing standard
heparin treatment with a combination of
trapidil, a
drug with anti-
platelet-derived growth factor (PDGF) activity, and
ticlopidine, a
platelet aggregation inhibitor. Ninety patients with
cirrhosis who received a transjugular shunt were randomized, and 84 patients completed the trial. Group 1 (n = 42) received a bolus of
heparin (12 to 24 U/kg) at shunt placement, followed by 1 week of intravenous and 4 weeks of subcutaneous
heparin treatment. Group 2 (n = 42) received the same
heparin bolus, followed by a 1-day intravenous
heparin treatment and a 6-month treatment with
trapidil (400 mg/d) and
ticlopidine (250 mg/d). Shunt function was assessed by duplex-sonography and angiography.
Stenoses were classified according to their location as type 1 (within the
stent) and type 2 (in the draining hepatic vein). The estimated rate of overall
stenoses (intention-to-treat analysis) at 1 year showed a significant reduction in patients receiving
trapidil and
ticlopidine (group 2) as compared with
heparin (33 vs. 57%; P =.047). There was no difference in the estimated 1-year rate of type 1
stenoses between the two groups, but there was a significant reduction in type 2
stenoses (group 1: 58%, group 2: 19%; P =.016). The treatment effect continued after withdrawal of the drugs and was accompanied by a decreased incidence of rebleeding. The study demonstrates that the incidence of type 2
stenosis of the transjugular shunt can be reduced by combined inhibition of platelet aggregation and PDGF activity. The findings may be of relevance not only for the transjugular shunt, but also for other
stent applications, e.g., vascular and biliary, as well as for bypass and shunt surgery.