Platelet Aggregation and Platelet–Derived Growth Factor Inhibition for Prevention of Insufficiency of the Transjugular Intrahepatic Portosystemic Shunt: A Randomized Study Comparing Trapidil Plus Ticlopidine With Heparin Treatment

Abstract

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. (HEPATOLOGY 1999;29:33-38.)The transjugular intrahepatic portosystemic shunt (TIPS) is compromised by a high rate of shunt insufficiency ranging from 44% to 84%, depending on the definition and mode of assessment of shunt function.

TIPS for the treatment of refractory ascites, hepatorenal syndrome and hepatic hydrothorax: a critical update

“…In many cases it may be due to bile duct involvement which may lead to ‘endotipsitis’ followed by intimal proliferation and thrombosis. It can be prevented by introducing covered stents and reduced by subcutaneous low molecular weight heparin for 4 weeks possibly together with trapidil and ticlopidin for 12 months 78. Our present practical approach in patients receiving bare stents is the adapted application of up to 2000 U of heparin intravenously during stent implantation followed by low molecular weight heparin subcutaneously during the index hospitalisation and a platelet aggregation inhibitor (eg, acetyl salicylic acid 100 mg/day for at least 6 months) in patients with platelet count >100 000/μl.…”

Transjugular intrahepatic portosystemic shunts: An update

“…The role of antiplatelet therapy was evaluated by Siegerstetter and colleagues in 90 patients who underwent TIPS. 63 The patients were randomly assigned to combination therapy with ticlopidine and trapidil for six months following TIPS versus 24 hours of intravenous heparin alone in the control group. The combined therapy reduced the rate of stenosis (19% versus 58% in the control group).…”

Transjugular Intrahepatic Portosystemic Shunt

“…Early shunt occlusion is mainly a result of thrombosis, which can be avoided by anticoagulation. Trapidil and ticlopidine with initial heparin reduced intimal proliferation [40] . Late shunt malfunction occurs in up to 80% of cases during follow-up.…”