Local drug delivery of Argatroban from a polymeric-metallic composite stent reduces platelet deposition in a swine coronary model

Thrombus formation after intracoronary stent implantation provides a stimulus for neointimal hyperplasia and if excessive can result in stent thrombosis. We tested the hypothesis that local delivery of an antithrombin drug from a polymeric-metallic stent inhibits platelet thrombus formation. An uncoated metal slotted tube, a jellyroll slotted metal stent with an Argatroban-loaded polymeric sleeve, and a jellyroll slotted metal stent with a drug-leached polymeric sleeve were randomly deployed into the coronary arteries of eight juvenile farm swine. Platelet deposition in the stented segments was determined at 2 hr using autologous ¹¹¹Indium oxime-labeled platelets. Platelet deposition was significantly less in the Argatroban- loaded stents compared to the Argatroban-leached stents (1.40 x 10⁸ platelets/cm² vs. 26.8 x 10⁸ platelets/cm²; P = 0.005). When corrected for differences in the metal surface area exposed to blood, platelet deposition was significantly lower in the Argatroban-loaded stent (1.74 ± 1.95 x 10⁸/cm²) compared to the Argatroban-leached stent (33.5 ± 39.1 x 10⁸/cm²; P = 0.005) and the uncoated metal stent (36.2 ± 73.3 x 10⁸/cm²; P = 0.006). In this coronary stent thrombosis model Argatroban has local antithrombotic properties when delivered with a polymer-metallic stent. Improved polymeric designs may reduce risk of thrombus deposition at the site of stent implantation.